Neuroblastoma
Conditions
Brief summary
The overall goal of this real-world data collection is to assess demographic, clinical characteristics and real-world effectiveness of pediatric neuroblastoma patients treated with lorlatinib through the expanded access program.
Interventions
DRUGlorlatinib
Oral
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
0 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient receives lorlatinib through Pfizer's expanded access program for treatment of ALK+ neuroblastoma. * HCP documentation of at least one tumor assessment of response after patient has had at least one dose of lorlatinib * Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
Exclusion criteria
* Any patient who does not meet any of the inclusion criteria defined in the previous section.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) | From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Tumor response was collected by the data collection tool (DCT) and responses included complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). As per International Neuroblastoma Response Criteria (INRC): CR=\<10 millimeter (mm) residual soft tissue at primary site and complete resolution of metaiodobenzylguanidine (MIBG) or \[18F\] fluorodeoxyglucose (FDG)/positron emission tomography (PET) uptake (for MIBG-nonavid tumors) at primary site; PR: \>=30% decrease in longest diameter (LD) of primary site & MIBG or FDG-PET uptake at primary site stable, improved, or resolved; SD: neither sufficient shrinkage for PR nor sufficient increase for PD at the primary site. PD greater than 20% increase in longest diameter taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study) and minimum absolute increase of 5 mm in longest dimension. One participant may have more than one tumor response. |
| Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis | From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Tumor response collected by DCT.Response included CR=resolution of all sites of disease; PR:\>=30% decrease in sum of diameter of non-primary (NP) target lesion (TL) compared to baseline, non-target (NT) lesion may be stable/small in size, no new lesion,\>=50% reduced MIBG absolute(abs) bone score (BS) (relative MIBG BS\>=0.1 to \<=0.5)/\>=50% reduced number of FDG-PET avid bone lesion; PD:new soft tissue lesion (STL) detected by computed tomography (CT)/magnetic resonance imaging (MRI) that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied, confirmed as neuroblastoma(NB)/ganglioneuroblastoma(GNB),new bone site:MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor/confirmed histologically as NB/GNB; \>20% increase in LD as reference smallest sum on study,minimum abs. increase of 5mm in sum of diameter of target STL; SD:No sufficient (suff) shrinkage for PR/suff increase for PD of NP lesion.One participant may have more than 1 tumor response |
| Number of Participants According to Bone Marrow Response | From start of lorlatinib treatment until CR, PR, MD or SD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Bone marrow response was collected by the DCT and responses included CR, PR, minimal disease (MD) and SD. As per INRC, CR= bone marrow with no tumor infiltration upon reassessment, independent of baseline tumor involvement; PD= bone marrow without tumor infiltration that became \> 5% tumor infiltration upon reassessment; or bone marrow with tumor infiltration that increased by \> 2 fold and had \> 20% tumor infiltration upon reassessment; MD= Bone marrow with less than or equal to (\<=) 5% tumor infiltration and remained \> 0 to \<= 5% tumor infiltration upon reassessment; or bone marrow with no tumor infiltration that became \<= 5% tumor infiltration upon reassessment; or bone marrow with \>20% tumor infiltration that had \> 0 to \<= 5% tumor infiltration upon reassessment and SD= bone marrow with tumor infiltration that remained positive with \> 5% tumor infiltration upon reassessment but did not meet CR, MD or PD criteria. |
| Number of Participants According to Health Care Professional (HCP) Reported Objective Response | From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Objective response was collected by the DCT and comprised of responses in 3 components based on INRC: primary tumor, soft tissue and bone metastases and bone marrow, CR=All components met criteria for CR; PR=PR in at least one component and all other components are either CR, MD (bone marrow), PR (soft tissue or bone), or not involved (NI); no component with PD; Minor response (MR) = PR or CR in at least one component but at least one other component; no component with PD; SD= SD in one component with no better than SD or NI in any other component; PD=Any component with PD. One participant may have more than one tumor response. |
| Number of Participants According to Derived Objective Response | From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Derived objective response was derived using rules based on responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD = Any component with PD. |
| Number of Participants With Best Overall Response Based on HCP Reported Objective Response | From start of lorlatinib treatment until CR, PR, MR, SD or PD, Up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Best overall response based on HCP reported objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=At least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = It is in one component with no better than SD or NI in any other component PD = Any component with PD. Best overall response taking the HCP reported response observed up to the data cut-off date for a specific milestone. |
| Number of Participants With Best Overall Response Based on Derived Objective Response | From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Best overall response based on derived objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR= PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD= Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD= Any component with PD. |
| Overall Response Rate Based on HCP Reported Response | From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). Two sided 95% confidence interval was based on Clopper Pearson method. |
| Overall Response Rate Based on Derived Response | From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). |
| Duration of HCP Reported Overall Responses | From date of CR or PR until earliest date of PD or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Duration of HCP reported overall response was derived as (earliest date of disease progression or death minus earliest date of complete or partial response + 1)/30.4. Participants who had not progressed or died were censored at their last assessment date prior to the data cut-off date. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved. PD=Any component with PD. |
| Progression Free Survival (PFS) | From start of lorlatinib treatment until disease progression or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | PFS was derived as (date of PD or death \[by any cause in the absence of PD\] minus date of first dose of lorlatinib plus 1) divided by 30.4. Participants who had not progressed or died were censored at the date of last contact prior to the data cut-off date. PD: new soft tissue lesion (STL) detected by CT/MRI that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied and confirmed as neuroblastoma (NB)/ganglioneuroblastoma (GNB), new bone site: MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor or confirmed histologically as NB/GNB; \>20% increase in LD as reference smallest sum on study (included baseline sum if that was the smallest on study), minimum abs increase of 5mm in sum of diameter of target STL. |
| Duration of Treatment | From start of lorlatinib treatment until treatment stop date or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study) | Duration of treatment was derived as treatment stop date minus treatment start date plus 1. Participants continuing treatment at the data cut-off date were censored based on the last recorded date when the participant was known to be continuing treatment prior to the data cut-off date. |
| Overall Survival | From date of first dose of lorlatinib until date of death or censoring date, up to maximum (max) of 36.2 months (M) of treatment (data was retrieved and evaluated retrospectively during approximately (approx.) 18 months of this study) | Overall survival was derived as date of death minus treatment start date plus 1. Participants who had not died were censored at the date of last contact prior to the data cut-off date. |
| Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events | From start of first dose of lorlatinib/date of informed consent(participant treated with lorlatinib) to atleast 28 day after last dose of lorlatinib to max 36.2M of treatment(data was retrieved, evaluated for approx. 18 month) | An AE is any untoward medical occurrence in participants administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. A SAE is any untoward medical occurrence in a participant administered a medicinal or nutritional product at any dose that: resulted in death, was life-threatening, required participant hospitalization or prolongation of hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) and resulted in congenital anomaly/birth defect. Relatedness to treatment was determined by investigator. |
Countries
Australia, New Zealand, Portugal, South Korea, Sweden, United States
Participant flow
Recruitment details
Participants with anaplastic lymphoma kinase (ALK)-aberrant neuroblastoma who initiated treatment with lorlatinib as part of expanded access program were included in this non-interventional study. Data was collected using the data collection tool (DCT).
Participants by arm
| Arm | Count |
|---|---|
| Lorlatinib Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other | 7 |
| Overall Study | Progressive disease | 7 |
Baseline characteristics
| Characteristic | Lorlatinib |
|---|---|
| Age, Continuous | 13.23 Years STANDARD_DEVIATION 11.553 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 15 |
| other Total, other adverse events | 12 / 15 |
| serious Total, serious adverse events | 6 / 15 |
Outcome results
Primary
Duration of HCP Reported Overall Responses
Duration of HCP reported overall response was derived as (earliest date of disease progression or death minus earliest date of complete or partial response + 1)/30.4. Participants who had not progressed or died were censored at their last assessment date prior to the data cut-off date. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved. PD=Any component with PD.
Time frame: From date of CR or PR until earliest date of PD or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Duration of HCP Reported Overall Responses | 21.7 Months |
Primary
Duration of Treatment
Duration of treatment was derived as treatment stop date minus treatment start date plus 1. Participants continuing treatment at the data cut-off date were censored based on the last recorded date when the participant was known to be continuing treatment prior to the data cut-off date.
Time frame: From start of lorlatinib treatment until treatment stop date or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Duration of Treatment | 16.2 Months |
Primary
Number of Participants According to Bone Marrow Response
Bone marrow response was collected by the DCT and responses included CR, PR, minimal disease (MD) and SD. As per INRC, CR= bone marrow with no tumor infiltration upon reassessment, independent of baseline tumor involvement; PD= bone marrow without tumor infiltration that became \> 5% tumor infiltration upon reassessment; or bone marrow with tumor infiltration that increased by \> 2 fold and had \> 20% tumor infiltration upon reassessment; MD= Bone marrow with less than or equal to (\<=) 5% tumor infiltration and remained \> 0 to \<= 5% tumor infiltration upon reassessment; or bone marrow with no tumor infiltration that became \<= 5% tumor infiltration upon reassessment; or bone marrow with \>20% tumor infiltration that had \> 0 to \<= 5% tumor infiltration upon reassessment and SD= bone marrow with tumor infiltration that remained positive with \> 5% tumor infiltration upon reassessment but did not meet CR, MD or PD criteria.
Time frame: From start of lorlatinib treatment until CR, PR, MD or SD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants According to Bone Marrow Response | CR | 2 Participants |
| Lorlatinib | Number of Participants According to Bone Marrow Response | PR | 0 Participants |
| Lorlatinib | Number of Participants According to Bone Marrow Response | MD | 1 Participants |
| Lorlatinib | Number of Participants According to Bone Marrow Response | SD | 0 Participants |
| Lorlatinib | Number of Participants According to Bone Marrow Response | Missing | 12 Participants |
Primary
Number of Participants According to Derived Objective Response
Derived objective response was derived using rules based on responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD = Any component with PD.
Time frame: From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants According to Derived Objective Response | CR | 2 Participants |
| Lorlatinib | Number of Participants According to Derived Objective Response | PR | 0 Participants |
| Lorlatinib | Number of Participants According to Derived Objective Response | MR | 0 Participants |
| Lorlatinib | Number of Participants According to Derived Objective Response | PD | 8 Participants |
| Lorlatinib | Number of Participants According to Derived Objective Response | Missing | 1 Participants |
| Lorlatinib | Number of Participants According to Derived Objective Response | Not Evaluable | 4 Participants |
Primary
Number of Participants According to Health Care Professional (HCP) Reported Objective Response
Objective response was collected by the DCT and comprised of responses in 3 components based on INRC: primary tumor, soft tissue and bone metastases and bone marrow, CR=All components met criteria for CR; PR=PR in at least one component and all other components are either CR, MD (bone marrow), PR (soft tissue or bone), or not involved (NI); no component with PD; Minor response (MR) = PR or CR in at least one component but at least one other component; no component with PD; SD= SD in one component with no better than SD or NI in any other component; PD=Any component with PD. One participant may have more than one tumor response.
Time frame: From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants According to Health Care Professional (HCP) Reported Objective Response | CR | 5 Participants |
| Lorlatinib | Number of Participants According to Health Care Professional (HCP) Reported Objective Response | PR | 7 Participants |
| Lorlatinib | Number of Participants According to Health Care Professional (HCP) Reported Objective Response | MR | 1 Participants |
| Lorlatinib | Number of Participants According to Health Care Professional (HCP) Reported Objective Response | SD | 5 Participants |
| Lorlatinib | Number of Participants According to Health Care Professional (HCP) Reported Objective Response | PD | 9 Participants |
Primary
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue)
Tumor response was collected by the data collection tool (DCT) and responses included complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). As per International Neuroblastoma Response Criteria (INRC): CR=\<10 millimeter (mm) residual soft tissue at primary site and complete resolution of metaiodobenzylguanidine (MIBG) or \[18F\] fluorodeoxyglucose (FDG)/positron emission tomography (PET) uptake (for MIBG-nonavid tumors) at primary site; PR: \>=30% decrease in longest diameter (LD) of primary site & MIBG or FDG-PET uptake at primary site stable, improved, or resolved; SD: neither sufficient shrinkage for PR nor sufficient increase for PD at the primary site. PD greater than 20% increase in longest diameter taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study) and minimum absolute increase of 5 mm in longest dimension. One participant may have more than one tumor response.
Time frame: From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) | CR | 3 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) | PR | 3 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) | SD | 5 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) | PD | 2 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) | Missing | 7 Participants |
Primary
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis
Tumor response collected by DCT.Response included CR=resolution of all sites of disease; PR:\>=30% decrease in sum of diameter of non-primary (NP) target lesion (TL) compared to baseline, non-target (NT) lesion may be stable/small in size, no new lesion,\>=50% reduced MIBG absolute(abs) bone score (BS) (relative MIBG BS\>=0.1 to \<=0.5)/\>=50% reduced number of FDG-PET avid bone lesion; PD:new soft tissue lesion (STL) detected by computed tomography (CT)/magnetic resonance imaging (MRI) that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied, confirmed as neuroblastoma(NB)/ganglioneuroblastoma(GNB),new bone site:MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor/confirmed histologically as NB/GNB; \>20% increase in LD as reference smallest sum on study,minimum abs. increase of 5mm in sum of diameter of target STL; SD:No sufficient (suff) shrinkage for PR/suff increase for PD of NP lesion.One participant may have more than 1 tumor response
Time frame: From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis | CR | 5 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis | PR | 5 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis | SD | 5 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis | PD | 7 Participants |
| Lorlatinib | Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis | Missing | 2 Participants |
Primary
Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events
An AE is any untoward medical occurrence in participants administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. A SAE is any untoward medical occurrence in a participant administered a medicinal or nutritional product at any dose that: resulted in death, was life-threatening, required participant hospitalization or prolongation of hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) and resulted in congenital anomaly/birth defect. Relatedness to treatment was determined by investigator.
Time frame: From start of first dose of lorlatinib/date of informed consent(participant treated with lorlatinib) to atleast 28 day after last dose of lorlatinib to max 36.2M of treatment(data was retrieved, evaluated for approx. 18 month)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events | AEs | 14 Participants |
| Lorlatinib | Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events | Treatment related AEs | 14 Participants |
| Lorlatinib | Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events | Serious AEs | 6 Participants |
| Lorlatinib | Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events | Serious Treatment related AEs | 3 Participants |
Primary
Number of Participants With Best Overall Response Based on Derived Objective Response
Best overall response based on derived objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR= PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD= Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD= Any component with PD.
Time frame: From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed were included in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants With Best Overall Response Based on Derived Objective Response | CR | 2 Participants |
| Lorlatinib | Number of Participants With Best Overall Response Based on Derived Objective Response | PD | 8 Participants |
| Lorlatinib | Number of Participants With Best Overall Response Based on Derived Objective Response | Missing | 5 Participants |
Primary
Number of Participants With Best Overall Response Based on HCP Reported Objective Response
Best overall response based on HCP reported objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=At least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = It is in one component with no better than SD or NI in any other component PD = Any component with PD. Best overall response taking the HCP reported response observed up to the data cut-off date for a specific milestone.
Time frame: From start of lorlatinib treatment until CR, PR, MR, SD or PD, Up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lorlatinib | Number of Participants With Best Overall Response Based on HCP Reported Objective Response | CR | 5 Participants |
| Lorlatinib | Number of Participants With Best Overall Response Based on HCP Reported Objective Response | PR | 3 Participants |
| Lorlatinib | Number of Participants With Best Overall Response Based on HCP Reported Objective Response | MR | 1 Participants |
| Lorlatinib | Number of Participants With Best Overall Response Based on HCP Reported Objective Response | SD | 3 Participants |
| Lorlatinib | Number of Participants With Best Overall Response Based on HCP Reported Objective Response | PD | 3 Participants |
Primary
Overall Response Rate Based on Derived Response
Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD).
Time frame: From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lorlatinib | Overall Response Rate Based on Derived Response | 13.3 Percentage of Participants |
Primary
Overall Response Rate Based on HCP Reported Response
Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). Two sided 95% confidence interval was based on Clopper Pearson method.
Time frame: From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lorlatinib | Overall Response Rate Based on HCP Reported Response | 53.3 Percentage of participants |
Primary
Overall Survival
Overall survival was derived as date of death minus treatment start date plus 1. Participants who had not died were censored at the date of last contact prior to the data cut-off date.
Time frame: From date of first dose of lorlatinib until date of death or censoring date, up to maximum (max) of 36.2 months (M) of treatment (data was retrieved and evaluated retrospectively during approximately (approx.) 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Overall Survival | 27.0 Months |
Primary
Progression Free Survival (PFS)
PFS was derived as (date of PD or death \[by any cause in the absence of PD\] minus date of first dose of lorlatinib plus 1) divided by 30.4. Participants who had not progressed or died were censored at the date of last contact prior to the data cut-off date. PD: new soft tissue lesion (STL) detected by CT/MRI that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied and confirmed as neuroblastoma (NB)/ganglioneuroblastoma (GNB), new bone site: MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor or confirmed histologically as NB/GNB; \>20% increase in LD as reference smallest sum on study (included baseline sum if that was the smallest on study), minimum abs increase of 5mm in sum of diameter of target STL.
Time frame: From start of lorlatinib treatment until disease progression or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)
Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lorlatinib | Progression Free Survival (PFS) | 17.8 Months |