TY - JOUR
T1 - Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1‒positive, advanced non‒small-cell lung cancer in the KEYNOTE-010 study
AU - Herbst, Roy S.
AU - Garon, Edward B.
AU - Dong-Wan, Kim
AU - Cho, Byoung Chul
AU - Perez-Gracia, Jose L.
AU - Ji-Youn, Han
AU - Arvis, Catherine Dubos
AU - Majem, Margarita
AU - Forster, Martin D.
AU - Monnet, Isabelle
AU - Novello, Silvia
AU - Szalai, Zsuzsanna
AU - Gubens, Matthew A.
AU - Wu-Chou, Su
AU - Ceresoli, Giovanni Luca
AU - Samkari, Ayman
AU - Jensen, Erin H.
AU - Lubiniecki, Gregory M.
AU - Baas, Paul
N1 - Publisher Copyright:
© 2020 by American Society of Clinical Oncology
PY - 2020/2
Y1 - 2020/2
N2 - PURPOSE In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) $ 50% and $ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS $ 50% and $ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P, .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P, .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.
AB - PURPOSE In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) $ 50% and $ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS $ 50% and $ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P, .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P, .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.
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U2 - 10.1200/JCO.19.02446
DO - 10.1200/JCO.19.02446
M3 - Article
C2 - 32078391
AN - SCOPUS:85082774749
SN - 0732-183X
VL - 38
SP - 1580
EP - 1591
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 14
ER -