TY - JOUR
T1 - Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/−bevacizumab for the first-line treatment of non-squamous NSCLC
T2 - A matching-adjusted indirect comparison
AU - Halmos, Balazs
AU - Burke, Thomas
AU - Kalyvas, Chrysostomos
AU - Vandormael, Kristel
AU - Frederickson, Andrew
AU - Piperdi, Bilal
N1 - Funding Information:
This study was funded by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc. , Kenilworth, NJ, USA . Medical writing and editorial assistance were provided by Adelphi Values Limited. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.
Funding Information:
This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing and editorial assistance were provided by Adelphi Values Limited. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.
Funding Information:
TB, BP, CK and KV are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. AF is an employee of precisionHEOR; precisionHEOR received funding from Merck & Co. as part of the research conducted. BH has received compensation as a consultant from Merck & Co., BMS, AstraZeneca, Boehringer-Ingelheim, Genentech, Guardant Health, TPT, Pfizer, Novartis and Amgen, and has received grants from Eli-Lilly, Merck, BMS, AstraZeneca, Boehringer-Ingelheim, Guardant Health, Pfizer, Novartis, AbbVie, Advaxis, GSK and Amgen.
Publisher Copyright:
© 2021 The Authors
PY - 2021/5
Y1 - 2021/5
N2 - Objectives: Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations. Materials and methods: A matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; N = 59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum chemotherapy; N = 410) and published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; N = 451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; N = 356). To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab + chemotherapy in KN021 G/KN189 were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy from IMpower 130 or atezolizumab + chemotherapy + bevacizumab from IMpower 150. Outcomes included overall survival (OS), blinded independent review-assessed progression-free survival (PFS) and objective response rate (ORR). OS and PFS follow-up were truncated to the trial with shorter follow-up. Sensitivity analyses were conducted without truncation of follow-up of OS and PFS. Results: After matching for cross-trial differences, the effective sample size of pembrolizumab + chemotherapy was 428 and 389 for the IMpower 130 and IMpower 150 comparisons, respectively. The estimated HRs (95 % CIs) of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (0.67,0.95) and 0.79 (0.67,0.93) with regard to OS and PFS, respectively. For pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, the estimated HR (95 % CIs) was 0.86 (0.72,1.03) for OS and 0.81 (0.68,0.96) for PFS. For ORR, the estimated risk ratio (95 % CI) and the risk difference (95 % CI) was 0.9 (0.8,1.1) and -3.5 % (-10.0,3.1) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy, respectively, and 0.8 (0.7,0.9) and -12.2 % (-19.6,-4.8) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes. Conclusion: MAIC results showed a significantly better OS and PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy and a significantly better PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy + bevacizumab.
AB - Objectives: Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations. Materials and methods: A matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; N = 59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum chemotherapy; N = 410) and published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; N = 451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; N = 356). To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab + chemotherapy in KN021 G/KN189 were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy from IMpower 130 or atezolizumab + chemotherapy + bevacizumab from IMpower 150. Outcomes included overall survival (OS), blinded independent review-assessed progression-free survival (PFS) and objective response rate (ORR). OS and PFS follow-up were truncated to the trial with shorter follow-up. Sensitivity analyses were conducted without truncation of follow-up of OS and PFS. Results: After matching for cross-trial differences, the effective sample size of pembrolizumab + chemotherapy was 428 and 389 for the IMpower 130 and IMpower 150 comparisons, respectively. The estimated HRs (95 % CIs) of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (0.67,0.95) and 0.79 (0.67,0.93) with regard to OS and PFS, respectively. For pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, the estimated HR (95 % CIs) was 0.86 (0.72,1.03) for OS and 0.81 (0.68,0.96) for PFS. For ORR, the estimated risk ratio (95 % CI) and the risk difference (95 % CI) was 0.9 (0.8,1.1) and -3.5 % (-10.0,3.1) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy, respectively, and 0.8 (0.7,0.9) and -12.2 % (-19.6,-4.8) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes. Conclusion: MAIC results showed a significantly better OS and PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy and a significantly better PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy + bevacizumab.
KW - Atezolizumab
KW - Comparative effectiveness
KW - Indirect treatment comparison
KW - Matching-adjusted indirect comparison
KW - Non-small cell lung cancer
KW - Pembrolizumab
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U2 - 10.1016/j.lungcan.2021.03.020
DO - 10.1016/j.lungcan.2021.03.020
M3 - Article
C2 - 33839603
AN - SCOPUS:85103755508
SN - 0169-5002
VL - 155
SP - 175
EP - 182
JO - Lung Cancer
JF - Lung Cancer
ER -
