Abstract 1026P
Background
CheckMate 227 is a phase III clinical trial designed to evaluate the efficacy of nivolumab plus ipilimumab vs platinum doublet chemotherapy in patients with stage IV or recurrent non-small cell lung cancer (NSCLC) previously untreated for advanced disease. Some patients in the chemotherapy arm subsequently switched to an immunotherapy due to toxicity or progressive disease. We update overall survival estimates by adjusting for potential biases introduced by treatment switching from chemotherapy to subsequent immunotherapy.
Methods
The Inverse Probability of Censoring Weights (IPCW) method that adjusts the treatment effect estimates in the presence of informative censoring was applied to adjust OS for treatment switching in the ITT population as a post hoc analysis based on 3-year follow up data. The IPCW method, being well recognized by health authorities, was considered as the base case. Other treatment switching adjustment methods were explored as sensitivity analysis. Exploratory analyses were also conducted in select subgroups.
Results
In part 1 of the trial, a total of 1166 patients (583 each arm) were included in the analysis. 235 (40.3%) patients in the chemotherapy arm switched to an immunotherapy. Median OS was 17.1 months (95% CI: 15.5 to 20.0) for the nivolumab plus ipilimumab arm and 14.0 months (95% CI: 12.6-15.4 months) for the chemotherapy arm. After adjustment for treatment switching, the median OS for the chemotherapy arm was 10.8 months (95% CI: 9.2 -12.8). The hazard ratio (HR) of nivolumab plus ipilimumab versus chemotherapy was 0.74 (95% CI: 0.65 to 0.85), which after adjustment reduced to 0.62 (95% CI: 0.53 to 0.73).
Conclusions
Based on 3-year follow up data from CheckMate 227, adjusting for treatment switching biases in the chemotherapy arm resulted in a numerically greater estimated relative OS benefit with nivolumab plus ipilimumab over chemotherapy in previously untreated patients, with advanced NSCLC without EGFR/ALK aberrations than in the unadjusted analysis.
Clinical trial identification
NCT02477826.
Editorial acknowledgement
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Roche. T. De: Financial Interests, Institutional, Full or part-time Employment: Parexel; Financial Interests, Institutional, Other, Received research grants/funds from BMS to conduct this research: Bristol Myers Squibb. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag International NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President ASEICA (Spanish Association of Cancer Research); Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. Y. Yuan, A. Lee, N. Varol, J. Penrod: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. A. Chaudhary: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb.