Pembrolizumab plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction cancer: KEYNOTE-859 Q-TWiST analysis.

[AIMS] In KEYNOTE-859, pembrolizumab plus chemotherapy significantly improved overall survival (OS) versus placebo plus chemotherapy for participants with untreated locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma, with manageable safety. This post hoc analysis assessed Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST).

[PARTICIPANTS AND METHODS] Survival time was grouped into three health states: TOX (time with any grade ≥3 adverse event [AE] before disease progression), TWiST (time before PD or death without grade ≥3 AEs), and REL (time from PD to death). Q-TWiST was the sum of restricted mean survival time (RMST) in each state, weighted by utilities estimated using the EQ-5D-5L questionnaire. Relative gains in Q-TWiST ≥15% were considered "clearly clinically important."

[RESULTS] RMST was longer in TOX (2.30 months [95% CI, 1.28 to 3.44]) and TWiST (1.90 months [95% CI, -0.02 to 3.79]) and shorter in REL (-0.28 months [95% CI, -2.43 to 2.01]) with pembrolizumab plus chemotherapy versus chemotherapy at month 56, for a relative Q-TWiST gain of 20.90% (US algorithm) or 18.38% (standardized algorithm).

[CONCLUSIONS] A clearly clinically important Q-TWiST gain was observed with pembrolizumab plus chemotherapy versus chemotherapy in all participants.

[CLINICAL TRIALS REGISTRATION] www.ClinicalTrials.gov identifier is NCT03675737.