Summary
Five Year Lung Cancer Survival Update: Pembrolizumab continued to improve OS than docetaxel in patients with PD-L1 TPS ≥50% and TPS ≥1%.
Five Year Lung Cancer Survival Update Introduction
Five year lung cancer survival update based on clinical trial data. In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study.
Five Year Lung Cancer Survival Update Methods
Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m2 once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis.
Five Year Lung Cancer Survival Update Results
A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab.
Five Year Lung Cancer Survival Update Conclusions
Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.
Five Year Lung Cancer Survival Update Introduction
Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), promotes T cell-mediated antitumor activity by inhibiting the interaction between PD-1 and its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2).1 Pembrolizumab has been found to improve overall survival (OS) compared with standard chemotherapy in the first- and second-line or later settings among patients with advanced or metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥1% and to improve OS when combined with platinum-based chemotherapy in patients with metastatic NSCLC regardless of PD-L1 TPS in the first-line setting.2, 3, 4, 5, 6, 7The primary analysis of the phase 2/3 KEYNOTE-010 study (data cutoff, September 30, 2015; median follow-up, 13.1 mo) showed significantly improved OS with pembrolizumab monotherapy (2 mg/kg or 10 mg/kg once every 3 weeks) versus docetaxel once every 3 weeks in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and PD-L1 TPS ≥1%.2 The hazard ratios (HRs) for OS were 0.54 (95% confidence interval [CI]: 0.38‒0.77) with pembrolizumab 2 mg/kg and 0.50 (95% CI: 0.36‒0.70) with pembrolizumab 10 mg/kg in patients with PD-L1 TPS ≥50% and 0.71 (95% CI: 0.58‒0.88) and 0.61 (95% CI: 0.49‒0.75), respectively, in patients with PD-L1 TPS ≥1%.2 Because OS was comparable for the two pembrolizumab doses, data were pooled for later analyses. In previously reported updated analyses with median follow-up of 31.0 and 42.6 months, pembrolizumab continued to show improvement in OS over docetaxel in patients with PD-L1 TPS ≥50% and TPS ≥1%.8,9We report an updated analysis of efficacy and safety outcomes for the intent-to-treat population in KEYNOTE-010 with approximately 5 years of follow-up from randomization to data cutoff, an additional 2 years of follow-up since previous analysis.9 In addition, outcomes are reported for the 79 patients who completed 35 cycles/2 years of pembrolizumab treatment (as specified in the study protocol and consistent with the pembrolizumab prescribing information10) and for the 21 patients who received second-course pembrolizumab. For the first time, we report the findings from an exploratory biomarker analysis of the prevalence and association with outcomes of tissue tumor mutational burden (tTMB) among patients in KEYNOTE-010.
