HRQOL in Patients With Advanced BTC Who Received Pembrolizumab With GemCis in the KEYNOTE-966 study

September 2023, Vol 4, No 3
The articles in this issue of CCA News include highlights from the ASCO 2023 Annual Meeting, June 2-6, 2023; Chicago, IL.

Patients with biliary tract cancer (BTC) generally have a poor prognosis, and due to tumor- and treatment-related factors, including pain, discomfort, fatigue, and general unwell feeling, patients often have a decreased health-related quality of life (HRQOL), which can limit their ability to complete daily activities.1 Often, a patient’s HRQOL may decrease as their disease becomes more advanced, in part due to treatments in the late-stage setting, so it is important to ensure new therapeutic approaches do not worsen HRQOL.1,2 Although the phase 3 KEYNOTE-966 study, which evaluated the addition of pembrolizumab to gemcitabine/cisplatin (GemCis) in patients with advanced BTC, demonstrated a significant and clinically meaningful improvement in overall survival, the impact of this combination therapy on a patient’s HRQOL is unknown.3 At the 2023 ASCO meeting, Changhoon Yoo, MD, PhD, presented results from a prespecified exploratory HRQOL analysis from the KEYNOTE-966 study.2

In KEYNOTE-966, 1069 patients from 175 medical centers around the world were randomly assigned 1:1 to pembrolizumab plus GemCis or pembrolizumab plus placebo.3 HRQOL was measured by 3 questionnaires: the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (global health status [GHS]/QOL, physical functioning [PF], and role functioning [RF]), EORTC QLQ-BIL21 (jaundice and pain), and the EuroQol Group questionnaire EQ-5D-5L (visual analog scale [VAS]).2

The analysis population included all treated patients who completed ≥1 HRQOL assessment for the specific end point. The primary end points were change from baseline (BL) to latest time point with ≥60% completion rate and ≥80% compliance rate for EORTC QLQ-C30, EORTC QLQ-BIL21 scores, and EQ-5D-5L VAS; and time to confirmed deterioration (TDDa) in EORTC QLQ-C30 GHS/QOL, PF, and RF domains and EORTC QLQ-BIL21 jaundice and pain domains.2 A constrained longitudinal analysis model was used to compare the least squares mean (LSM) score changes from BL to week 18.2 The questionnaire compliance rate was >87% from BL to week 18 in both treatment groups.2 The LSM changes from BL to week 18 for all 3 questionnaires were similar between both treatment groups (Tables 1-3).2 Similar changes were seen from BL to week 18 in EORTC QLQ-C30 GHS/QOL, PF, and RF; EORTC QLQ-BIL21 jaundice and pain; and EQ-5D-5L VAS between the 2 treatment groups.2 TDDa was also similar in both arms; no significant differences were found in TDDa in EORTC QLQ-C30 GHS/QOL, PF, or RF domains, or EORTC QLQ-BIL21 jaundice and pain domains.2

The HRQOL data from the KEYNOTE-966 study demonstrated that HRQOL was maintained and did not worsen when pembrolizumab was added to the standard GemCis regimen. The previously reported safety and efficacy data and the newly released HRQOL data from the study support pembrolizumab in combination with GemCis as a viable therapy option for patients with advanced BTC.2


  1. Patel N, Lie X, Gwaltney C, et al. Understanding patient experience in biliary tract cancer: a qualitative patient interview study. Oncol Ther. 2021;9(2):557-573.
  2. Yoo C, Finn RS, Klümpen HJ, et al. Health-related quality of life in the phase 3 KEYNOTE-966 study of pembrolizumab plus gemcitabine and cisplatin versus placebo plus gemcitabine and cisplatin for advanced biliary tract cancer. Presented at: ASCO 2023 Annual Meeting, June 2-6; Chicago, IL.
  3. Kelley R, Ueno M, Yoo C. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401(10391):1853-1865.

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