Objective: To characterize the benefit-risk profile of pemetrexed and platinum in combination with pembrolizumab in patients with non-squamous non-small cell lung cancer in the KEYNOTE-189 study, with reference to historical pemetrexed maintenance data from the PARAMOUNT, PRONOUNCE, and JVBL randomized studies. Materials and methods: To harmonize the treatment setting across the studies in our comparative analysis, we selected patients from KEYNOTE-189 who received ≥5 cycles of pemetrexed (pembrolizumab/pemetrexed/platinum, N = 310; placebo/pemetrexed/platinum, N = 135) and pooled data from PARAMOUNT (N = 359), PRONOUNCE (N = 98), and JVBL (N = 29) who received ≥5 cycles of pemetrexed (total, N = 486). For the 2 selected populations from KEYNOTE-189 and the pooled historical data, progression-free survival (PFS) was evaluated by Kaplan-Meier estimator and Cox proportional hazards model. Tumor response and grade ≥3 treatment-emergent adverse events (TEAEs) for the aforementioned population were summarized by descriptive statistics. Results: In the selected KEYNOTE-189 population with ≥5 cycles pemetrexed, median PFS was 9.3 months (95 % confidence interval [CI]: 9.0–11.1) in the pembrolizumab/pemetrexed/platinum arm and 6.6 months (95 % CI: 5.4–7.1) in the placebo/pemetrexed/platinum arm (unstratified hazard ratio: 0.53; 95 % CI: 0.42‒0.68; p ≤ 0.0001). In the pooled population with ≥5 cycles pemetrexed from historical trials, median PFS was 5.6 months (95 % CI: 4.6–5.8). Objective response rates were 58.7 % and 28.9 % in the pembrolizumab/pemetrexed/platinum and placebo/pemetrexed/platinum arms, respectively, of KEYNOTE-189 and 42.4 % in the pooled historical studies. The incidence of grade ≥3 TEAEs was similar in both arms of KEYNOTE-189 and in the pooled historical studies. Conclusion: Improved PFS was shown with pembrolizumab/pemetrexed/platinum compared with placebo/pemetrexed/platinum in the patient group with pemetrexed maintenance (≥5 cycles) in KEYNOTE-189. The PFS and safety profile of the control arm in KEYNOTE-189 were comparable with historical pemetrexed maintenance data.
- Continuous maintenance therapy
- Non-small cell lung cancer