Squamous Non-small Cell Lung Cancer
Conditions
Brief summary
This study aims to characterize the profile and outcomes for patients with Squamous Cell Carcinoma of the Lung (SqCC) who progress on 1L pembrolizumab in combination with platinum based chemotherapy and receive afatinib as second line (2L) therapy.
Interventions
DRUGSecond line (2L) afatinib
Afatinib
Chemotherapy
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of squamous or mixed histology non-small cell lung cancer * Treated with pembrolizumab in combination with platinum-based chemotherapy as initial therapy for advanced or metastatic disease (stage IIIB or IV) * First cycle of pembrolizumab received after 06/01/2018 * Permanently discontinued 1L pembrolizumab treatment * Initiated second-line treatment at least 3 months prior to the date of data collection, with either : * Afatinib * Any chemotherapy * Age ≥ 18 years
Exclusion criteria
-Received pembrolizumab in combination with platinum-based chemotherapy as part of an interventional clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time on Treatment With Afatinib or Chemotherapy During Second Line (2L) Treatment | From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated and up to 7.5 months for chemotherapy treated patients | Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment. |
| Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Histology Status | From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated patients | Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment. Patients treated with afatinib were analysed for their histology status and categorized into a squamous cell - or mixed histology treatment group. |
| Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Epidermal Growth Factor Receptor (EGFR) Mutation Status | From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated patients | Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment. |
| Number of Patients With Severe Immune-related Adverse Events (irAEs) of Specific Interest During Second-line Treatment | From the start of second-line treatment to the end of follow-up, up to 15 months | Chart abstractors (i.e. the patients treating physician) were asked to abstract information regarding severe (grade 3 or higher) irAEs of specific interest (including pneumonitis, colitis, hepatitis, interstitial lung disease, higher indeterminate pulmonary events, death, or discontinuation of therapy due to toxicity) during first line (1L) treatment and second line (2L) for both patients treated with afatinib in 2L and those treated with chemotherapy in 2L. Providers/abstractors were asked only if these specific immune related events occurred. |
Countries
United States
Participant flow
Recruitment details
This retrospective, non-interventional, multi-site cohort study utilized existing data from the electronic medical records of patients with advanced or metastatic Squamous Cell Carcinoma (SqCC) of the lung treated with first-line pembrolizumab in combination with platinum-doublet chemotherapy, followed by second-line afatinib or chemotherapy.
Pre-assignment details
All patients (pts) aged ≥18 years, initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy. All pts had started second-line treatment with either afatinib or any CT at least 3 months prior to date of data collection. Maximum follow-up for any pts was approx 15 months. Pts were excluded if they had received pembrolizumab in combination with platinum-based CT as part of an interventional clinical trial.
Participants by arm
| Arm | Count |
|---|---|
| Second-line Afatinib Treatment Group Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection. | 99 |
| Second-line Chemotherapy Treatment Group Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection. | 101 |
| Total | 200 |
Baseline characteristics
| Characteristic | Second-line Afatinib Treatment Group | Second-line Chemotherapy Treatment Group | Total |
|---|---|---|---|
| Age, Continuous | 67 Years | 66 Years | 67 Years |
| Eastern Cooperative Oncology Group Performance Status at initiation of second line (2L) treatment ECOG 0/1 | 45 Participants | 50 Participants | 95 Participants |
| Eastern Cooperative Oncology Group Performance Status at initiation of second line (2L) treatment ECOG ≥ 2 | 54 Participants | 51 Participants | 105 Participants |
| Epidermal growth factor receptor (EGFR) mutation status EGFR mutation negative | 28 Participants | 33 Participants | 61 Participants |
| Epidermal growth factor receptor (EGFR) mutation status EGFR mutation positive | 39 Participants | 5 Participants | 44 Participants |
| Epidermal growth factor receptor (EGFR) mutation status Not tested / unknown | 32 Participants | 63 Participants | 95 Participants |
| Most common comorbidities at initiation of second line treatment Any comorbidity | 98 Participants | 88 Participants | 186 Participants |
| Most common comorbidities at initiation of second line treatment Cardiovascular disease | 23 Participants | 33 Participants | 56 Participants |
| Most common comorbidities at initiation of second line treatment Chronic pulmonary disease | 35 Participants | 49 Participants | 84 Participants |
| Most common comorbidities at initiation of second line treatment Depression | 27 Participants | 14 Participants | 41 Participants |
| Most common comorbidities at initiation of second line treatment Diabetes without chronic complications | 21 Participants | 16 Participants | 37 Participants |
| Most common comorbidities at initiation of second line treatment Hypertension | 62 Participants | 56 Participants | 118 Participants |
| Programmed death ligand 1 (PD-L1) expression level <1% | 26 Participants | 30 Participants | 56 Participants |
| Programmed death ligand 1 (PD-L1) expression level 1 to 49% | 55 Participants | 54 Participants | 109 Participants |
| Programmed death ligand 1 (PD-L1) expression level >50% | 15 Participants | 6 Participants | 21 Participants |
| Programmed death ligand 1 (PD-L1) expression level Not tested | 3 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 23 Participants | 53 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) White | 59 Participants | 73 Participants | 132 Participants |
| Radiation therapy First line or prior | 14 Participants | 10 Participants | 24 Participants |
| Radiation therapy Second line | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Female | 43 Participants | 34 Participants | 77 Participants |
| Sex: Female, Male Male | 56 Participants | 67 Participants | 123 Participants |
| Sites of metastatic disease at initiation of second line treatment Adrenal gland | 26 Participants | 48 Participants | 74 Participants |
| Sites of metastatic disease at initiation of second line treatment Blood and bone marrow | 41 Participants | 47 Participants | 88 Participants |
| Sites of metastatic disease at initiation of second line treatment Brain | 14 Participants | 10 Participants | 24 Participants |
| Sites of metastatic disease at initiation of second line treatment Contralateral lung nodule | 51 Participants | 43 Participants | 94 Participants |
| Sites of metastatic disease at initiation of second line treatment Intra-abdominal lymph nodes | 19 Participants | 14 Participants | 33 Participants |
| Sites of metastatic disease at initiation of second line treatment Liver | 65 Participants | 69 Participants | 134 Participants |
| Sites of metastatic disease at initiation of second line treatment Pleura (nodules, effusion) | 24 Participants | 21 Participants | 45 Participants |
| Smoking history Current smoker | 16 Participants | 19 Participants | 35 Participants |
| Smoking history Former smoker | 71 Participants | 82 Participants | 153 Participants |
| Smoking history Never smoked | 12 Participants | 0 Participants | 12 Participants |
| Tumor histology Mixed histology | 35 Participants | 3 Participants | 38 Participants |
| Tumor histology Squamous cell only | 64 Participants | 98 Participants | 162 Participants |
| Tumor stage at initial diagnosis Tumor stage IIIB | 7 Participants | 3 Participants | 10 Participants |
| Tumor stage at initial diagnosis Tumor stage I to IIIA | 13 Participants | 8 Participants | 21 Participants |
| Tumor stage at initial diagnosis Tumor stage IV | 79 Participants | 90 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 99 |
| other Total, other adverse events | 37 / 99 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Number of Patients With Severe Immune-related Adverse Events (irAEs) of Specific Interest During Second-line Treatment
Chart abstractors (i.e. the patients treating physician) were asked to abstract information regarding severe (grade 3 or higher) irAEs of specific interest (including pneumonitis, colitis, hepatitis, interstitial lung disease, higher indeterminate pulmonary events, death, or discontinuation of therapy due to toxicity) during first line (1L) treatment and second line (2L) for both patients treated with afatinib in 2L and those treated with chemotherapy in 2L. Providers/abstractors were asked only if these specific immune related events occurred.
Time frame: From the start of second-line treatment to the end of follow-up, up to 15 months
Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with either afatinib or any CT at least 3 months prior to date of data collection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Second-line Afatinib Treatment Group | Number of Patients With Severe Immune-related Adverse Events (irAEs) of Specific Interest During Second-line Treatment | 6 Participants |
| Second-line Chemotherapy Treatment Group | Number of Patients With Severe Immune-related Adverse Events (irAEs) of Specific Interest During Second-line Treatment | 0 Participants |
Primary
Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Epidermal Growth Factor Receptor (EGFR) Mutation Status
Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment.
Time frame: From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated patients
Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with afatinib at least 3 months prior to date of data collection. Only afatinib treated patients with an EGFR mutation positive or negative status were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Second-line Afatinib Treatment Group | Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Epidermal Growth Factor Receptor (EGFR) Mutation Status | 7.4 months |
| Second-line Chemotherapy Treatment Group | Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Epidermal Growth Factor Receptor (EGFR) Mutation Status | 5.9 months |
Primary
Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Histology Status
Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment. Patients treated with afatinib were analysed for their histology status and categorized into a squamous cell - or mixed histology treatment group.
Time frame: From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated patients
Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with afatinib at least 3 months prior to date of data collection. Only patients treated with afatinib and with squamous cell - or mixed histology were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Second-line Afatinib Treatment Group | Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Histology Status | 5.8 months |
| Second-line Chemotherapy Treatment Group | Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Histology Status | 8.1 months |
Primary
Time on Treatment With Afatinib or Chemotherapy During Second Line (2L) Treatment
Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment.
Time frame: From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated and up to 7.5 months for chemotherapy treated patients
Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with either afatinib or any CT at least 3 months prior to date of data collection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Second-line Afatinib Treatment Group | Time on Treatment With Afatinib or Chemotherapy During Second Line (2L) Treatment | 7.3 months |
| Second-line Chemotherapy Treatment Group | Time on Treatment With Afatinib or Chemotherapy During Second Line (2L) Treatment | 4.2 months |