PIK3CA-Related Overgrowth Spectrum (PROS)
Conditions
Keywords
alpelisib, PIK3CA, BYL719, PROS, Retrospective chart review study, EPIK-P1
Brief summary
The study was a site-based retrospective non-interventional medical chart review of pediatric and adult male and female patients with PIK3CA-Related Overgrowth Spectrum (PROS) who initiated alpelisib at least 24 weeks before the cut-off date at a MAP site. The study cut-off date was 09-Mar-2020. Patient-level data were abstracted from medical charts of all eligible patients at all participating sites. Study completion date refers to the last date data was extracted. Information from patients treated with alpelisib was used to describe the efficacy and safety of alpelisib in PROS patients.
Detailed description
The index date (baseline) is defined as the date of alpelisib initiation. The study period is the period from the index date up to the most recent data available at the time of the cut-off date. The maximum follow-up was 187 weeks.
Interventions
OTHERalpelisib
Retrospective observational case-only study. There is no treatment allocation. Patients with severe or life-threatening PROS who have received alpelisib as part of a compassionate use program were invited to participate.
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient (adult or pediatric) is ≥ 2 years of age * Patient has a physician confirmed/documented diagnosis of PROS * Patient has a documented evidence of a mutation in the PIK3CA gene * Patient's condition was assessed by the treating physician as severe or life threatening and treatment was deemed necessary * Patient has been treated with at least one dose of alpelisib, initiated on or before 23-Sep-2019 (i.e. at least 24 weeks before the cut-off date of the 09-Mar-2020) * Patient has medical chart history available during enrollment in the Novartis MAP * Patient (or parent/guardian in case of pediatric patient) consented to participate in the study (as required by local ethics regulations) Inclusion criteria for MAP enrollment (assessed at the time of alpelisib initiation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Responders and Non-responders at Week 24 | Index date and week 24 or 6 months (± 4 weeks) | Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in the Sum of All Measurable Lesion Volume | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) | Percent change in the sum of all measurable (target and non-target) lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. End of study: patients were followed up to a maximum of 187 weeks As no measurable non-target lesions were identified, the results for changes in the sum of all measurable (target and non-target) lesion volume were identical to the results presented for measurable target lesion. |
| Percent Change in the Sum of All Measurable Non-target Lesion Volume | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) | Percent change in the sum of all measurable non-target lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. |
| Mean Duration of Response (DoR) | Up to 187 weeks | Duration of response is defined as the time from first documented response, to the date of the first documented disease progression or death due to any cause. Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. Disease progression is defined as an increase of any individual target lesions of ≥ 20% in volume from previous assessment, progression of non-target PIK3CA Related Overgrowth Spectrum (PROS) lesions or appearance of a new PROS lesion. |
| Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Up to 187 weeks | Number of participants with concomitant PIK3CA Related Overgrowth Spectrum (PROS)-related non-drug treatments and other medical interventions by reason for discontinuation. A patient may have multiple information, but was counted only once in type of other supportive non-drug treatment if more than one type in this category has been reported. |
| Participants With Concomitant PROS-related Medications Over Time | Index date, week 24 and end of study | Number of participants with at least one concomitant utilization of PIK3CA Related Overgrowth Spectrum (PROS)-related medication. End of study: patients were followed up to a maximum of 187 weeks. Results are provided for the full study population as planned and documented in the protocol and SAP, and not by age group. |
| Number of PROS-related Completed Surgeries During the Study Period | Up to 187 weeks | Number of surgeries by reason of surgery. A patient may have multiple anatomical sites of surgery and types of surgery on the same day. |
| Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Index date and week 24 or 6 months (± 4 weeks) | Improvement in PIK3CA Related Overgrowth Spectrum (PROS) signs and symptoms was defined based on Common Toxicity Criteria (CTC) grade reduction or resolution of the event from index date. CTC is a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. The Common Terminology Criteria for Adverse Events (CTCAE) system is a product of the US National Cancer Institute (NCI). For this study, version 4.03 was used |
| Change in Performance Status Score | Index date and week 24 or 6 months (± 4 weeks) | Participants with a change in performance status score (ECOG, Karnofsky, Lansky) between the index date and week 24. Patients completed one questionnaire (ECOG, Karnofsky or Lansky) based on physicians choice. The Eastern Cooperative Oncology Group (ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death. The Karnofsky Performance Score (KPS) and Lansky score run from 0 to 100, where 0 is death and 100 is perfect health. For the ECOG scale, improvement is defined as a decrease by at least 1 point and and worsening is defined as an increase by at least 1 point. For the Karnofsky and Lansky scale, improvement is defined as an increase by at least 20 points and worsening is defined as a decrease by at least 20 points. If neither of the criteria for improvement or worsening is met, then it is considered stable. |
| Functional Status - Mobility Assessment | Up to 187 weeks | Change in functional status: Mobility severity assessment measured up to the judgment of the investigator. A patient may have multiple information |
| Percent Change in the Sum of Measurable Target Lesion Volume | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) | Percent change in the sum of measurable target lesion (1 to 3 lesions) volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date: (baseline) was defined as the date of alpelisib initiation End of study: patients were followed up to a maximum of 187 weeks. |
| Change From Index Date in Functional Status - Work Status | Index date, week 24 and end of study | Change in functional status: Work status assessment during the study period (no attendance, part-time, full-time or unemployed). Improvement is defined as a shift from reporting of No attendance to Part-time or Full time, from Part-time to Full-time, as well as from Unemployed to Part-time or Full-time work. Worsening is defined as a shift from reporting of Part-time to No attendance, Full-time to Part-time or No attendance as well as Part-time or Full-time to Unemployed status. Change in score is only applicable if both index date and post-index date information are available. If a patient has more than 1 score reported within the same time window, the worst is considered. If neither of the criteria for improvement or worsening is met, then it is considered stable. |
| Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Up to 187 weeks | Hospitalizations starting on or after the start of study treatment (index date) or starting prior to and continuing after the start of study treatment are summarized. |
| Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Up to 187 weeks | Worst post-index date hematology abnormalities based on Common Toxicity Criteria (CTC) grades during the study period. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized. |
| Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | 187 weeks | Worst post-index date biochemistry abnormalities based on Common Toxicity Criteria (CTC) grades. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized. |
| Notable Vital Sign Values During the Study Period - Pediatric Patients | End of study (up to week 187) | Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥95th percentile of the age and height group Low Systolic blood pressure: ≤5th percentile of the age and height group. High diastolic blood pressure: ≥95th percentile of the age and height group Low diastolic blood pressure: ≤5th percentile of the age and height group. High pulse rate (bpm): 2-3 years: \>128; 3-4 years: \>123; 4-6 years: \>117; 6-8 years: \>111; 8-12years: \>103; 12-15 years: \>96; ≥15 years: \>92 Low pulse rate (bpm): 2-3 years: \<92; 3-4 years: \<86; 4-6 years: \<81; 6-8 years: \<74; 8-12 years: \<67; 12-15 years: \<62; ≥15 years: \<58. High weight: increase from baseline of ≥2 Body mass index (BMI) for age percentile categories Low weight: decrease from baseline of ≥2 BMI-for-age percentile categories |
| Notable Vital Sign Values During the Study Period - Adult Patients | End of study (up to week 187) | Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥180 mmHg and increase ≥20 mmHg Low systolic blood pressure: ≤90 mmHg and decrease ≥20 mmHg. High diastolic blood pressure: ≥105 mmHg and increase ≥15 mmHg Low diastolic blood pressure: ≤50 mmHg and decrease ≥15 mmHg. High pulse rate: ≥120 bpm and increase ≥15 bpm Low pulse rate: ≤ 50 bpm and decrease ≥15 bpm. High weight: Increase ≥10% Low weight: Decrease ≥10% |
| Number of Participants With Notable ECG Values. | Up to week 187 | Notable Electrocardiogram (ECG) values during the study period |
| Growth and Development in Pediatric Population | Week 24 or 6 months (± 4 weeks) | Assessed in patients who were aged \<18 years at the time of alpelisib initiation. SDS (standard deviation scores) for height and BMI are obtained from the WHO Growth Charts, and SDS for height and weight velocity are obtained from Baumgartner et al. (1986). Height or weight velocity is a variable derived from the measurement of height or weight at different times and represents the increase in height or weight during a fixed period. SD- scores are used to describe how far a measurement is from the median (average). Weight-for-age reference data are not available beyond age 10. |
| Overview of Number of Patients With Adverse Events (AEs) | Up to 187 weeks | A patient with multiple severity grades for an AE is only counted under the maximum grade. All grades includes any AEs with missing grade. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. |
| Change From Index Date in Functional Status - School Status During the Study Period | Index date, week 24 and end of study (up to 187 weeks) | Change in functional status: School status during the study period (no attendance, part-time or full time). Improvement is defined as a shift from reporting of No attendance to Part-time as well as , Part-time or No attendance to Full-time; Worsening is defined as a shift from reporting of Part-time to No attendance, as well as from Full-time to Part-time or No attendance. If neither of the criteria for improvement or worsening is met, then it is considered stable. |
Countries
Australia, France, Ireland, Spain, United States
Participant flow
Recruitment details
Participants were from Australia (1), France (50), Ireland (1), Spain (3) and United States (2)
Participants by arm
| Arm | Count |
|---|---|
| Pediatric Patients Pediatric patients (\< 18 years) treated with alpelisib | 39 |
| Adult Patients Adult patients (\>= 18 years) treated with alpelisib | 18 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No efficiency | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Subject decision | 1 | 2 |
Baseline characteristics
| Characteristic | Pediatric Patients | Adult Patients | Total |
|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 4.84 | 27.8 years STANDARD_DEVIATION 8.34 | 15.5 years STANDARD_DEVIATION 10.39 |
| Race/Ethnicity, Customized Not reported | 32 Participants | 18 Participants | 50 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 0 Participants | 7 Participants |
| Sex: Female, Male Female | 24 Participants | 9 Participants | 33 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 18 |
| other Total, other adverse events | 23 / 39 | 16 / 18 |
| serious Total, serious adverse events | 10 / 39 | 11 / 18 |
Outcome results
Primary
Percentage of Patients Responders and Non-responders at Week 24
Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions.
Time frame: Index date and week 24 or 6 months (± 4 weeks)
Population: Efficacy population: It is a subset of the Full study population. It included patients with at least one target lesion and with an imaging scan performed on the index date (or up to 24 weeks prior to the index date) for at least one target lesion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Patients | Percentage of Patients Responders and Non-responders at Week 24 | Responders | 30.4 Percentage of participants |
| Pediatric Patients | Percentage of Patients Responders and Non-responders at Week 24 | Non Responders | 69.6 Percentage of participants |
| Adult Patients | Percentage of Patients Responders and Non-responders at Week 24 | Responders | 55.6 Percentage of participants |
| Adult Patients | Percentage of Patients Responders and Non-responders at Week 24 | Non Responders | 44.4 Percentage of participants |
Secondary
Change From Index Date in Functional Status - School Status During the Study Period
Change in functional status: School status during the study period (no attendance, part-time or full time). Improvement is defined as a shift from reporting of No attendance to Part-time as well as , Part-time or No attendance to Full-time; Worsening is defined as a shift from reporting of Part-time to No attendance, as well as from Full-time to Part-time or No attendance. If neither of the criteria for improvement or worsening is met, then it is considered stable.
Time frame: Index date, week 24 and end of study (up to 187 weeks)
Population: Full study population: included all patients who satisfied the study inclusion criteria.~Only patients reporting school status at index date were included in the calculation of change
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | Improvement | 1 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | Stable | 28 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | missing | 0 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | Worsening | 0 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | Improvement | 2 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | Stable | 27 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | missing | 0 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | Worsening | 0 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | Worsening | 0 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | Improvement | 0 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | Improvement | 2 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | Stable | 4 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | missing | 0 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | missing | 0 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | End of study | Stable | 2 Participants |
| Adult Patients | Change From Index Date in Functional Status - School Status During the Study Period | Change 24 weeks | Worsening | 0 Participants |
Secondary
Change From Index Date in Functional Status - Work Status
Change in functional status: Work status assessment during the study period (no attendance, part-time, full-time or unemployed). Improvement is defined as a shift from reporting of No attendance to Part-time or Full time, from Part-time to Full-time, as well as from Unemployed to Part-time or Full-time work. Worsening is defined as a shift from reporting of Part-time to No attendance, Full-time to Part-time or No attendance as well as Part-time or Full-time to Unemployed status. Change in score is only applicable if both index date and post-index date information are available. If a patient has more than 1 score reported within the same time window, the worst is considered. If neither of the criteria for improvement or worsening is met, then it is considered stable.
Time frame: Index date, week 24 and end of study
Population: Full study population: included all patients who satisfied the study inclusion criteria.~Only adult patients reporting work status at index date were included in the calculation of change.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change 24 weeks | Improvement | 0 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change 24 weeks | Worsening | 1 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change 24 weeks | Stable | 6 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change 24 weeks | Missing | 1 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change end of study | Improvement | 5 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change end of study | Worsening | 0 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change end of study | Stable | 2 Participants |
| Pediatric Patients | Change From Index Date in Functional Status - Work Status | Change end of study | Missing | 1 Participants |
Secondary
Change in Performance Status Score
Participants with a change in performance status score (ECOG, Karnofsky, Lansky) between the index date and week 24. Patients completed one questionnaire (ECOG, Karnofsky or Lansky) based on physicians choice. The Eastern Cooperative Oncology Group (ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death. The Karnofsky Performance Score (KPS) and Lansky score run from 0 to 100, where 0 is death and 100 is perfect health. For the ECOG scale, improvement is defined as a decrease by at least 1 point and and worsening is defined as an increase by at least 1 point. For the Karnofsky and Lansky scale, improvement is defined as an increase by at least 20 points and worsening is defined as a decrease by at least 20 points. If neither of the criteria for improvement or worsening is met, then it is considered stable.
Time frame: Index date and week 24 or 6 months (± 4 weeks)
Population: Full study population: included all patients who satisfied the study inclusion criteria.~Only patients with performance status (ECOG, Karnofsky, Lansky) assessed at the index date were included in the calculation of change
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Change in Performance Status Score | Stable | 9 Participants |
| Pediatric Patients | Change in Performance Status Score | Improved | 8 Participants |
| Pediatric Patients | Change in Performance Status Score | Worsened | 0 Participants |
| Pediatric Patients | Change in Performance Status Score | Not reported | 16 Participants |
| Adult Patients | Change in Performance Status Score | Not reported | 7 Participants |
| Adult Patients | Change in Performance Status Score | Stable | 1 Participants |
| Adult Patients | Change in Performance Status Score | Worsened | 0 Participants |
| Adult Patients | Change in Performance Status Score | Improved | 6 Participants |
Secondary
Functional Status - Mobility Assessment
Change in functional status: Mobility severity assessment measured up to the judgment of the investigator. A patient may have multiple information
Time frame: Up to 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria.~Only patients with at least one mobility assessment were included in the severity assessment.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Pediatric Patients | Functional Status - Mobility Assessment | Mild impairment | 0 Affected regions |
| Pediatric Patients | Functional Status - Mobility Assessment | Severe impairment | 0 Affected regions |
| Pediatric Patients | Functional Status - Mobility Assessment | Moderate impairment | 1 Affected regions |
| Pediatric Patients | Functional Status - Mobility Assessment | Missing | 0 Affected regions |
| Pediatric Patients | Functional Status - Mobility Assessment | No impairment | 0 Affected regions |
| Adult Patients | Functional Status - Mobility Assessment | Missing | 1 Affected regions |
| Adult Patients | Functional Status - Mobility Assessment | No impairment | 1 Affected regions |
| Adult Patients | Functional Status - Mobility Assessment | Mild impairment | 1 Affected regions |
| Adult Patients | Functional Status - Mobility Assessment | Moderate impairment | 2 Affected regions |
| Adult Patients | Functional Status - Mobility Assessment | Severe impairment | 1 Affected regions |
Secondary
Growth and Development in Pediatric Population
Assessed in patients who were aged \<18 years at the time of alpelisib initiation. SDS (standard deviation scores) for height and BMI are obtained from the WHO Growth Charts, and SDS for height and weight velocity are obtained from Baumgartner et al. (1986). Height or weight velocity is a variable derived from the measurement of height or weight at different times and represents the increase in height or weight during a fixed period. SD- scores are used to describe how far a measurement is from the median (average). Weight-for-age reference data are not available beyond age 10.
Time frame: Week 24 or 6 months (± 4 weeks)
Population: Full study population: included all pediatric patients who satisfied the study inclusion criteria. Only patients with SD-score available are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Patients | Growth and Development in Pediatric Population | Weight velocity SDS | -0.2 SD-score | Standard Deviation 2.86 |
| Pediatric Patients | Growth and Development in Pediatric Population | Height SDS | -0.1 SD-score | Standard Deviation 1.23 |
| Pediatric Patients | Growth and Development in Pediatric Population | Height velocity SDS | 0.1 SD-score | Standard Deviation 5.01 |
| Pediatric Patients | Growth and Development in Pediatric Population | BMI SDS | 0.8 SD-score | Standard Deviation 1.21 |
Secondary
Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient
Hospitalizations starting on or after the start of study treatment (index date) or starting prior to and continuing after the start of study treatment are summarized.
Time frame: Up to 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Patients | Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Number of times a patient has been hospitalized | 1.8 Number of hospitalizations | Standard Deviation 1.03 |
| Pediatric Patients | Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Number of times a patient has been hospitalized due to PROS | 1.1 Number of hospitalizations | Standard Deviation 0.35 |
| Adult Patients | Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Number of times a patient has been hospitalized | 1.7 Number of hospitalizations | Standard Deviation 0.82 |
| Adult Patients | Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Number of times a patient has been hospitalized due to PROS | 1.0 Number of hospitalizations | Standard Deviation 0 |
Secondary
Mean Duration of Response (DoR)
Duration of response is defined as the time from first documented response, to the date of the first documented disease progression or death due to any cause. Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. Disease progression is defined as an increase of any individual target lesions of ≥ 20% in volume from previous assessment, progression of non-target PIK3CA Related Overgrowth Spectrum (PROS) lesions or appearance of a new PROS lesion.
Time frame: Up to 187 weeks
Population: Efficacy population: It is a subset of the Full study population. This analysis only applied to responders with documented disease progression or death due to any cause.
Secondary
Notable Vital Sign Values During the Study Period - Adult Patients
Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥180 mmHg and increase ≥20 mmHg Low systolic blood pressure: ≤90 mmHg and decrease ≥20 mmHg. High diastolic blood pressure: ≥105 mmHg and increase ≥15 mmHg Low diastolic blood pressure: ≤50 mmHg and decrease ≥15 mmHg. High pulse rate: ≥120 bpm and increase ≥15 bpm Low pulse rate: ≤ 50 bpm and decrease ≥15 bpm. High weight: Increase ≥10% Low weight: Decrease ≥10%
Time frame: End of study (up to week 187)
Population: Full study population: included all patients who satisfied the study inclusion criteria. Only adult patients were included in this analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Systolic blood pressure | 17 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Systolic blood pressure | 3 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Diastolic blood pressure | 12 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Diastolic blood pressure | 2 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Pulse rate | 15 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Pulse rate | 10 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Weight | 0 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Weight | 1 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Weight | 6 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Systolic blood pressure | 0 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Pulse rate | 1 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Systolic blood pressure | 0 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Weight | 0 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | High Diastolic blood pressure | 2 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Pulse rate | 0 Participants |
| Adult Patients | Notable Vital Sign Values During the Study Period - Adult Patients | Low Diastolic blood pressure | 0 Participants |
Secondary
Notable Vital Sign Values During the Study Period - Pediatric Patients
Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥95th percentile of the age and height group Low Systolic blood pressure: ≤5th percentile of the age and height group. High diastolic blood pressure: ≥95th percentile of the age and height group Low diastolic blood pressure: ≤5th percentile of the age and height group. High pulse rate (bpm): 2-3 years: \>128; 3-4 years: \>123; 4-6 years: \>117; 6-8 years: \>111; 8-12years: \>103; 12-15 years: \>96; ≥15 years: \>92 Low pulse rate (bpm): 2-3 years: \<92; 3-4 years: \<86; 4-6 years: \<81; 6-8 years: \<74; 8-12 years: \<67; 12-15 years: \<62; ≥15 years: \<58. High weight: increase from baseline of ≥2 Body mass index (BMI) for age percentile categories Low weight: decrease from baseline of ≥2 BMI-for-age percentile categories
Time frame: End of study (up to week 187)
Population: Full study population: included all patients who satisfied the study inclusion criteria. Only pediatric patients were included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | Low Systolic blood pressure | 3 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | High Systolic blood pressure | 17 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | High Diastolic blood pressure | 12 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | Low Diastolic blood pressure | 2 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | High Pulse rate | 15 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | Low Pulse rate | 10 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | High Weight | 0 Participants |
| Pediatric Patients | Notable Vital Sign Values During the Study Period - Pediatric Patients | Low Weight | 1 Participants |
Secondary
Number of Participants With Notable ECG Values.
Notable Electrocardiogram (ECG) values during the study period
Time frame: Up to week 187
Population: Full study population: included all patients who satisfied the study inclusion criteria. Only patients with ECG data are included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Number of Participants With Notable ECG Values. | QTcF New >450 to <=480 ms | 1 Participants |
| Pediatric Patients | Number of Participants With Notable ECG Values. | QT Increase >30 to <=60 ms | 1 Participants |
| Pediatric Patients | Number of Participants With Notable ECG Values. | QT New >480 to <=500 ms | 0 Participants |
| Adult Patients | Number of Participants With Notable ECG Values. | QT New >480 to <=500 ms | 1 Participants |
| Adult Patients | Number of Participants With Notable ECG Values. | QTcF New >450 to <=480 ms | 1 Participants |
| Adult Patients | Number of Participants With Notable ECG Values. | QT Increase >30 to <=60 ms | 0 Participants |
Secondary
Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry
Worst post-index date biochemistry abnormalities based on Common Toxicity Criteria (CTC) grades. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized.
Time frame: 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Gamma Glutamyl Transferase Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Glucose Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Calcium Corrected Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Magnesium Increase - Grade 3/4 | 1 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Albumin Decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Magnesium Decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Calcium Corrected Decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Phosphate Decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Aspartate Aminotransferase Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Potassium Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Cholesterol Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Potassium Decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Alanine Aminotransferase Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Sodium Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Creatine Kinase Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Sodium Decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Bilirubin Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Triglycerides Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Creatinine Increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Urate Increase - Grade 3/4 | 1 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Alkaline Phosphatase Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Urate Increase - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Alanine Aminotransferase Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Albumin Decrease - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Alkaline Phosphatase Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Aspartate Aminotransferase Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Bilirubin Increase - Grade 3/4 | 2 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Calcium Corrected Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Calcium Corrected Decrease - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Cholesterol Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Creatine Kinase Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Creatinine Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Glucose Increase - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Magnesium Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Magnesium Decrease - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Phosphate Decrease - Grade 3/4 | 2 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Potassium Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Potassium Decrease - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Sodium Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Sodium Decrease - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Triglycerides Increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Gamma Glutamyl Transferase Increase - Grade 3/4 | 0 Participants |
Secondary
Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology
Worst post-index date hematology abnormalities based on Common Toxicity Criteria (CTC) grades during the study period. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized.
Time frame: Up to 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Platelets, decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Activated partial thromboplastin time, increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Fibrinogen, decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Hemoglobin, decrease - Grade 3/4 | 2 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Leukocytes, increase - Grade 3/4 | 1 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Leukocytes, decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Lymphocytes, increase - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Lymphocytes, decrease - Grade 3/4 | 0 Participants |
| Pediatric Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Neutrophils, decrease - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Lymphocytes, decrease - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Leukocytes, decrease - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Activated partial thromboplastin time, increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Platelets, decrease - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Fibrinogen, decrease - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Lymphocytes, increase - Grade 3/4 | 0 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Hemoglobin, decrease - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Neutrophils, decrease - Grade 3/4 | 1 Participants |
| Adult Patients | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Leukocytes, increase - Grade 3/4 | 0 Participants |
Secondary
Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms
Improvement in PIK3CA Related Overgrowth Spectrum (PROS) signs and symptoms was defined based on Common Toxicity Criteria (CTC) grade reduction or resolution of the event from index date. CTC is a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. The Common Terminology Criteria for Adverse Events (CTCAE) system is a product of the US National Cancer Institute (NCI). For this study, version 4.03 was used
Time frame: Index date and week 24 or 6 months (± 4 weeks)
Population: Full study population: included all patients who satisfied the study inclusion criteria. For the assessment of improvement for the individual items, only patients with the symptom at the index date were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Vascular malformation improved by week 24 | 20 Participants |
| Pediatric Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Limb asymmetry improved by week 24 | 11 Participants |
| Pediatric Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Disseminated intravascular coagulation improved by week 24 | 11 Participants |
| Pediatric Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Pain improved by week 24 | 11 Participants |
| Pediatric Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Fatigue improved by week 24 | 22 Participants |
| Adult Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Pain improved by week 24 | 9 Participants |
| Adult Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Fatigue improved by week 24 | 10 Participants |
| Adult Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Vascular malformation improved by week 24 | 10 Participants |
| Adult Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Disseminated intravascular coagulation improved by week 24 | 5 Participants |
| Adult Patients | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Limb asymmetry improved by week 24 | 9 Participants |
Secondary
Number of PROS-related Completed Surgeries During the Study Period
Number of surgeries by reason of surgery. A patient may have multiple anatomical sites of surgery and types of surgery on the same day.
Time frame: Up to 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Patients | Number of PROS-related Completed Surgeries During the Study Period | Other | 4 Surgeries |
| Pediatric Patients | Number of PROS-related Completed Surgeries During the Study Period | Disease improvement | 2 Surgeries |
| Pediatric Patients | Number of PROS-related Completed Surgeries During the Study Period | Disease progression (not radiologically confirmed) | 3 Surgeries |
| Adult Patients | Number of PROS-related Completed Surgeries During the Study Period | Other | 2 Surgeries |
| Adult Patients | Number of PROS-related Completed Surgeries During the Study Period | Disease improvement | 1 Surgeries |
| Adult Patients | Number of PROS-related Completed Surgeries During the Study Period | Disease progression (not radiologically confirmed) | 0 Surgeries |
Secondary
Overview of Number of Patients With Adverse Events (AEs)
A patient with multiple severity grades for an AE is only counted under the maximum grade. All grades includes any AEs with missing grade. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.
Time frame: Up to 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs - All grades | 10 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose interruption - All grades | 2 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs - Grade ≥ 3 | 3 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose interruption - Grade ≥ 3 | 0 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | Adverse events - Grade ≥ 3 | 4 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to treatment discontinuation | 0 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose reduction - All grades | 0 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs treatment-related - All grades | 0 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | Adverse events - All grades | 31 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs treatment-related - Grade ≥ 3 | 0 Participants |
| Pediatric Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose reduction - Grade ≥ 3 | 0 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs treatment-related - Grade ≥ 3 | 1 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | Adverse events - All grades | 16 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | Adverse events - Grade ≥ 3 | 9 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs - Grade ≥ 3 | 9 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose reduction - All grades | 3 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose reduction - Grade ≥ 3 | 0 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose interruption - All grades | 3 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to dose interruption - Grade ≥ 3 | 2 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | AEs leading to treatment discontinuation | 0 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs treatment-related - All grades | 3 Participants |
| Adult Patients | Overview of Number of Patients With Adverse Events (AEs) | SAEs - All grades | 11 Participants |
Secondary
Participants With Concomitant PROS-related Medications Over Time
Number of participants with at least one concomitant utilization of PIK3CA Related Overgrowth Spectrum (PROS)-related medication. End of study: patients were followed up to a maximum of 187 weeks. Results are provided for the full study population as planned and documented in the protocol and SAP, and not by age group.
Time frame: Index date, week 24 and end of study
Population: Full study population: included all patients who satisfied the study inclusion criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Participants With Concomitant PROS-related Medications Over Time | Index date | 34 Participants |
| Pediatric Patients | Participants With Concomitant PROS-related Medications Over Time | 24 weeks | 30 Participants |
| Pediatric Patients | Participants With Concomitant PROS-related Medications Over Time | End of study | 25 Participants |
Secondary
Percent Change in the Sum of All Measurable Lesion Volume
Percent change in the sum of all measurable (target and non-target) lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. End of study: patients were followed up to a maximum of 187 weeks As no measurable non-target lesions were identified, the results for changes in the sum of all measurable (target and non-target) lesion volume were identical to the results presented for measurable target lesion.
Time frame: Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187)
Population: Full study population: included all patients who satisfied the study inclusion criteria.~At each time point, only patients with a value at both index date and that time point are included in the calculation of change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Patients | Percent Change in the Sum of All Measurable Lesion Volume | 12 weeks | -18.59 % change in the sum of lesion vol. | Standard Deviation 16.837 |
| Pediatric Patients | Percent Change in the Sum of All Measurable Lesion Volume | 52 weeks | -13.91 % change in the sum of lesion vol. | Standard Deviation 19.206 |
| Pediatric Patients | Percent Change in the Sum of All Measurable Lesion Volume | 24 weeks | -11.20 % change in the sum of lesion vol. | Standard Deviation 19.987 |
| Pediatric Patients | Percent Change in the Sum of All Measurable Lesion Volume | End of study | -36.47 % change in the sum of lesion vol. | Standard Deviation 46.137 |
| Pediatric Patients | Percent Change in the Sum of All Measurable Lesion Volume | 4 weeks | -11.64 % change in the sum of lesion vol. | Standard Deviation 12.869 |
| Adult Patients | Percent Change in the Sum of All Measurable Lesion Volume | End of study | -17.38 % change in the sum of lesion vol. | Standard Deviation 11.679 |
| Adult Patients | Percent Change in the Sum of All Measurable Lesion Volume | 4 weeks | -11.78 % change in the sum of lesion vol. | Standard Deviation 8.154 |
| Adult Patients | Percent Change in the Sum of All Measurable Lesion Volume | 12 weeks | -19.77 % change in the sum of lesion vol. | Standard Deviation 5.128 |
| Adult Patients | Percent Change in the Sum of All Measurable Lesion Volume | 24 weeks | -19.69 % change in the sum of lesion vol. | Standard Deviation 15.375 |
| Adult Patients | Percent Change in the Sum of All Measurable Lesion Volume | 52 weeks | -6.52 % change in the sum of lesion vol. | Standard Deviation 2.614 |
Secondary
Percent Change in the Sum of All Measurable Non-target Lesion Volume
Percent change in the sum of all measurable non-target lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation.
Time frame: Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187)
Population: Full study population: included all patients who satisfied the study inclusion criteria. Only patients with non-target lesion are included in the analysis.~Zero patients were included in this measure since no measurable non-target lesions were identified by independent central radiology review (ICRR) at the index date.
Secondary
Percent Change in the Sum of Measurable Target Lesion Volume
Percent change in the sum of measurable target lesion (1 to 3 lesions) volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date: (baseline) was defined as the date of alpelisib initiation End of study: patients were followed up to a maximum of 187 weeks.
Time frame: Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187)
Population: Full study population: included all patients who satisfied the study inclusion criteria.~At each time point, only patients with a value at both index date and that time point are included in the calculation of change
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 12 weeks | -18.59 % change in the sum of lesion vol. | Standard Deviation 16.837 |
| Pediatric Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 52 weeks | -13.91 % change in the sum of lesion vol. | Standard Deviation 19.206 |
| Pediatric Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 24 weeks | -11.20 % change in the sum of lesion vol. | Standard Deviation 19.987 |
| Pediatric Patients | Percent Change in the Sum of Measurable Target Lesion Volume | End of study | -36.47 % change in the sum of lesion vol. | Standard Deviation 46.137 |
| Pediatric Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 4 weeks | -11.64 % change in the sum of lesion vol. | Standard Deviation 12.869 |
| Adult Patients | Percent Change in the Sum of Measurable Target Lesion Volume | End of study | -17.38 % change in the sum of lesion vol. | Standard Deviation 11.679 |
| Adult Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 4 weeks | -11.78 % change in the sum of lesion vol. | Standard Deviation 8.154 |
| Adult Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 12 weeks | -19.77 % change in the sum of lesion vol. | Standard Deviation 5.128 |
| Adult Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 24 weeks | -19.69 % change in the sum of lesion vol. | Standard Deviation 15.375 |
| Adult Patients | Percent Change in the Sum of Measurable Target Lesion Volume | 52 weeks | -6.52 % change in the sum of lesion vol. | Standard Deviation 2.614 |
Secondary
Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments
Number of participants with concomitant PIK3CA Related Overgrowth Spectrum (PROS)-related non-drug treatments and other medical interventions by reason for discontinuation. A patient may have multiple information, but was counted only once in type of other supportive non-drug treatment if more than one type in this category has been reported.
Time frame: Up to 187 weeks
Population: Full study population: included all patients who satisfied the study inclusion criteria. Only patients who were under concomitant PROS-related non-drug treatments were included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Recovery | 12 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Completed the planned course of treatment | 4 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Unknown | 2 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Lack of efficacy | 1 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Other | 2 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Adverse event | 0 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Progressive disease | 0 Participants |
| Pediatric Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Subject decision | 0 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Subject decision | 1 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Recovery | 2 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Other | 0 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Completed the planned course of treatment | 7 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Progressive disease | 1 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Unknown | 1 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Adverse event | 1 Participants |
| Adult Patients | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Lack of efficacy | 1 Participants |