Three-year follow-up data from KEYNOTE-966: Pembrolizumab (pembro) plus gemcitabine and cisplatin (gem/cis) compared with gem/cis alone for patients (pts) with advanced biliary tract cancer (BTC).
Year: 2024
Type: conference-abstract
Abstract: 4093 Background: KEYNOTE-966 demonstrated that adding pembro to gem/cis provided a statistically significant, clinically meaningful improvement in OS as first-line therapy for BTC. After a median follow-up (ie, time from randomization to data cutoff) of 25.6 months (mo), median OS was 12.7 mo for pembro + gem/cis vs 10.9 mo with placebo + gem/cis (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72-0.95; P = 0.0034; data cutoff date December 15, 2022). We present updated efficacy and safety data after 11 mo of additional follow-up. Methods: Key eligibility criteria included age ≥18 years; previously untreated, histologically confirmed metastatic or unresectable locally advanced BTC measurable by RECIST v1.1; and ECOG PS 0 or 1. Pts were randomized 1:1 to pembro 200 mg or placebo Q3W for ≤35 cycles plus gem 1000 mg/m 2 on days 1 and 8 Q3W until PD and cis 25 mg/m 2 on days 1 and 8 for <8 cycles.Pts were stratified by region (Asia vs non-Asia), stage (locally advanced vs metastatic), and site of origin (gallbladder vs intrahepatic vs extrahepatic). The primary end point was OS; secondary end points were PFS, ORR, and DOR assessed per RECIST v1.1 by blinded independent central review, and safety. The data cutoff date for this analysis was November 14, 2023. Results: 1069 pts were randomized to pembro + gem/cis (n = 533) or placebo + gem/cis (n = 536). At a median follow-up of 36.6 mo (range, 29.2-49.4), the OS benefit of pembro + gem/cis was maintained (HR 0.86, 95% CI 0.75-0.98). Median OS was 12.7 mo (95% CI 11.5-13.6) for the pembro arm vs 10.9 mo (95% CI 9.9-11.6) for the placebo arm. At 24 mo, the OS rate was 24.6% (95% CI 21.0-28.3) in the pembro arm vs 19.2% (95% CI 16.0-22.6) in the placebo arm. OS in key subgroups continued to favor the pembro arm. Median PFS was 6.5 mo (95% CI 5.7-6.9) for the placebo arm vs 5.6 mo (95% CI 4.9-6.5) for the pembro arm (HR 0.85, 95% CI 0.75-0.97). ORR was 28.7% (n = 153) in the pembro arm vs 28.7% (n = 154) in the placebo arm. DOR was 8.3 mo (range: 1.2+ to 44.3+) for the pembro arm vs 6.9 mo (1.1+ to 41.1+) for the placebo arm; at 18 mo, estimates of ongoing response were 24% in the pembro arm vs 14% in the placebo arm. 378 (71.5%) out of 529 treated pts in the pembro arm had grade 3-5 treatment-related adverse events (AEs) vs 370 (69.3%) out of 534 treated pts in the placebo arm. 31 (5.9%) pts in the pembro arm died vs 50 (9.4%) in the placebo arm. There were no additional treatment-related deaths since the final analysis. Conclusions: With a median follow-up of 36.6 mo, the clinically meaningful improvement in OS with pembro + gem/cis was maintained, with no new safety signals, compared with placebo + gem/cis in pts with unresectable or advanced BTC. These data support pembro + gem/cis as first-line treatment for advanced BTC.
Source: Journal of Clinical Oncology
Authors: Richard S. Finn, Makoto Ueno, Changhoon Yoo, Zhenggang Ren, Junji Furuse, Robin Kate Kelley, Stephen Lam Chan, Julien Edeline, Heinz-Josef Klümpen, Thomas Yau, Chris Verslype, Masato Ozaka, Mohamed Bouattour, Joon Oh Park, Arndt Vogel, Juan W. Valle, Liis Starkopf, Usha Malhotra, Abby B. Siegel, Shukui Qin
Institutions: University of California, Los Angeles, Kanagawa Cancer Center, Asan Medical Center, University of Ulsan, Fudan University, Zhongshan Hospital, Kyorin University, University of California, San Francisco, Chinese University of Hong Kong, Prince of Wales Hospital, Centre Eugène Marquis, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, University of Hong Kong, Universitair Ziekenhuis Leuven, The Cancer Institute Hospital, Japanese Foundation For Cancer Research, Hôpital Beaujon, Assistance Publique – Hôpitaux de Paris, Samsung Medical Center, Sungkyunkwan University, Medizinische Hochschule Hannover, Cholangiocarcinoma Foundation, Merck & Co., Inc., Rahway, NJ, USA (United States), Nanjing University of Chinese Medicine, Nanjing General Hospital of Nanjing Military Command
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4399736253