Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.3 months. Based on these results, the objective of this study was to characterize real-world NSCLC patients who received second-line therapy after single-agent pembrolizumab. Methods: This was a retrospective cohort study considering stage IV NSCLC patients diagnosed with BC Cancer between 2018 and 2021 with PD-L1 ≥ 50% who received first-line single agent pembrolizumab. Patient demographics, cancer history, treatment administered, and survival were collected retrospectively. Descriptive statistics were produced. OS was calculated using Kaplan–Meier curves and compared using the log rank test. A multivariate model evaluated characteristics associated with the receipt of second-line therapy. Results: A total of 718 patients were diagnosed with Stage IV NSCLC and received at least one cycle of pembrolizumab. The median duration of treatment was 4.4 months, and the follow-up duration was 16.0 months. There were 567 (79%) patients who had disease progression, of whom 21% received second-line systemic therapy. Within the subset of patients with disease progression, the median duration of treatment was 3.0 months. It would be found that patients who received second-line therapy had better baseline ECOG performance status, were younger at diagnosis, and had a longer duration of pembrolizumab. Within the full population, the OS from the treatment initiation date was 14.0 months. OS was 5.6 months in patients who did not receive additional therapy after progression and 22.2 months in patients who received subsequent therapy. Baseline ECOG performance status was associated with improved OS in multivariate analysis. Conclusion: Based on this real-world Canadian population, 21% of patients received second-line systemic therapy, despite second-line therapy being associated with prolonged survival. In this real-world population, we found that 60% fewer patients received second-line systemic therapy when compared to KEYNOTE-024. Although differences always exist when comparing a clinical and non-clinical trial population, our findings suggest undertreating stage IV NSCLC patients.
Background: A fixed dose of 200 mg of pembrolizumab every 3 weeks (Q3W) is the standard of care for patients with stage IV non-small cell lung cancer (NSCLC) and PDL1 ≥50%. In April 2020, based on pharmacokinetic modeling without formal comparative studies, the FDA approved 400 mg every 6 weeks (Q6W). Pharmacokinetic studies also suggested comparable target engagement with weight-based and flat dosing for the respective schedules. The objective of this study was to determine if overall survival (OS) differs based on the Q3W vs. Q6W dosing schedule of pembrolizumab. Methods: BC Cancer patients with stage IV NSCLC and PDL1 ≥50% treated with pembrolizumab were retrospectively reviewed. Patients were treated with weight-based dosing, per institution standard, of pembrolizumab 2 mg/kg Q3W or 4 mg/kg Q6W. Patient demographics, treatment and outcome were recorded. Patients were assigned to Q3W or Q6W according to the schedule that was used for the majority of treatment (greater than 50%). Results: 718 patients with NSCLC and PDL1 ≥50% received first-line pembrolizumab between 2017 and2021, Q3W/Q6W dosing 677/41 patients. Baseline characteristics with respect to age, sex, smoking status, histology and performance status (PS) were similar between groups. In the multivariate model, including age, sex, PS and dosing schedule, the hazard ratio for death (HR) for OS Q3W vs. Q6W was 0.759 (p = 0.230). A 2:1 case-matched analysis for OS was performed, controlling for sex, age ± 5 years, PS and duration on pembrolizumab ± 2 months for Q3W vs. Q6W (n = 113) with a HR 0.834 (p = 0.500). Conclusions: There was no OS difference demonstrated with pembrolizumab dosing Q3W compared to Q6W in a multivariate analysis that included age, sex and PS. A case-matched analysis that controlled for these variables and for duration of treatment confirmed these findings. This study supports the use of Q6W pembrolizumab dosing, allowing for less frequent interactions with the medical system.
PURPOSE: Limited English-proficient (LEP) patients with non–small-cell lung cancer (NSCLC) may receive less palliative care services and more likely to receive aggressive end-of-life (EoL) care. Goals of this retrospective cohort study are to compare access to community palliative home care (CPHC), do not resuscitate (DNR) form completion, place of death, and health resource utilization at EoL between English-proficient (EP) and LEP patients with NSCLC in Vancouver, Canada. METHODS: All patients with advanced NSCLC referred in 2016 and received medical care were included. Patients were classified as LEP if seen with a medical interpreter. Descriptive statistics and univariate and multivariate analyses were used to compare the outcomes between the two groups. RESULTS: One hundred eighty-six patients were referred, 66% EP. Rates of CPHC referral and DNR form completion were the same for both groups (84% and 92%, P = 1.00). LEP patients received earlier access to CPHC (15 v 10 weeks before death, P = .039). Rates of ER visits within 6 months and 30 days of death were 0.89 for EP patients and 0.7 for LEP patients, P = .374, and 0.1 for EP patients and 0.13 for LEP patients, P = .244. Hospitalization rates within 6 months and 30 days of death were 1.4 for EP patients and 1.59 for LEP patients, P = .640, and 0.67 for EP patients and 0.81 for LEP patients, P = .091. EP patients were more likely to have a home death (26% v 14%), whereas LEP patients died in acute care (23% v 14%) or a tertiary palliative care unit (24% v 19%). This was not statistically significant ( P = .335). LEP patients had better median overall survival (8.5 v 5.4 months, P < .001), but when controlled by age, mutation, and EP status, only receipt of palliative-intent systemic therapy was statistically significant. CONCLUSION: EP and LEP patients with NSCLC have similar referral rates to CPHC, DNR form completion, and EoL health resource utilization. The measured EoL variables did not demonstrate significant disparities between EP and LEP patients.
Lung cancer is a leading cause of cancer-related mortality despite continued advances in diagnostic and therapeutic strategies. Although the development of immune checkpoint inhibitors has revolutionized the treatment landscape for advanced non–small cell lung cancer, many patients either have primary resistance to these agents or eventually develop secondary resistance necessitating a change to an alternate therapy. Understanding novel patterns of response to immunotherapy is crucial in determining appropriate selection and sequencing of treatment. Chemotherapy remains the standard of care in immunotherapy-refractory disease, but multiple trials are ongoing to explore the role of combination radioimmunotherapy and rechallenging with immunotherapy either alone or in combination with other antineoplastic agents.