TY - JOUR
T1 - Pemetrexed maintenance with or without pembrolizumab in non-squamous non-small cell lung cancer
T2 - A cross-trial comparison of KEYNOTE-189 versus PARAMOUNT, PRONOUNCE, and JVBL
AU - Garon, Edward B.
AU - Kim, Jong Seok
AU - Govindan, Ramaswamy
N1 - Funding Information:
E.B.G reports grants from AstraZeneca, Bristol-Myers Squibb, Dracen, EMD Serono, Genentech, Eli Lilly and Company, Novartis, Merck, Neon, Mirati, Dynavax, and Iovance, and personal fees from Dracen, EMD Serono, and Novartis. J.S.K. is an employee and owns stock in Eli Lilly and Company. R.G. R. reports consulting for GenePlus and his wife reports consulting for Horizon Pharmaceuticals.
Publisher Copyright:
© 2020 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Continuous maintenance therapy
KW - JVBL
KW - KEYNOTE-189
KW - Non-small cell lung cancer
KW - PARAMOUNT
KW - PRONOUNCE
KW - Pemetrexed
UR - http://www.scopus.com/inward/record.url?scp=85097237974&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2020.11.018
DO - 10.1016/j.lungcan.2020.11.018
M3 - Article
C2 - 33285468
AN - SCOPUS:85097237974
VL - 151
SP - 25
EP - 29
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -