Clinical outcomes of pembrolizumab plus gemcitabine and cisplatin in a Japanese institutional subgroup of KEYNOTE-966: a dexamethasone-minimizing supportive-care approach.

INTRODUCTION

KEYNOTE-966, a double-blinded randomized controlled phase III trial comparing pembrolizumab/placebo + gemcitabine + cisplatin (GC) for biliary tract cancer [BTC], demonstrated the efficacy and safety of addition of pembrolizumab to GC. The effect of steroid and antibiotics use on immune check-point inhibitors is still of interest.

METHODS

This was a post-hoc, exploratory institutional subgroup analysis of KEYNOTE-966. Dexamethasone was minimized for antiemetic prophylaxis, and antibiotics were administered selectively for cholangitis according to the institutional practice. Thirty-eight patients registered at our institution were randomly assigned to each treatment group. After the key was opened following completion of the protocol treatment in these patients, we compared the efficacy and safety in patients of Pembrolizumab+GC and those of Placebo+GC. We performed multivariable analysis using the Cox regression hazard model and inverse-probability weighting propensity score (IPW) analysis to adjust for between-group background differences.

RESULTS

It was found that there were 22 and 16 patients in the Pembrolizumab+GC and Placebo+GC groups, respectively. The hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) for the Pembrolizumab+GC group were 0.622 (95% confidence interval [CI], 0.318-1.217) and 0.360 (95% CI, 0.178-0.728), respectively; the objective response rates were 31.8% and 6.3%, respectively. The HR for OS and PFS in the multivariable and IPW analyses were numerically similar to those in the original analysis, which was better than that observed in the entire KEYNOTE-966 cohort.

DISCUSSION: Our experience of Pembrolizumab + GC over Placebo +GC generates a clinical question whether the efficacy of Pembrolizumab may be enhanced when antibiotics and antiemetic DEX are avoided.