Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. (December 2022)

• Record Type: Journal Article
• Authors: Huang, Min; O'Shaughnessy, Joyce; Haiderali, Amin; Pan, Wilbur; Hu, Peter; Chaudhuri, Mitashri; Le Bailly De Tilleghem, Celine; Cappoen, Nicolas; Fasching, Peter A.
• Is Part Of: European journal of cancer. Volume 177(2022)
• Page Start: 45
• Page End: 52
• Publication Date: 2022-12
• Subjects: Metastatic triple-negative breast cancer -- Pembrolizumab plus chemotherapy -- Quality-adjusted survival -- Q-TWiST; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.09.029
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Objective: In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population. Methods: The study used data from the final analysis of KN355. The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments of pembrolizumab plus chemotherapy versus chemotherapy alone. Patients' survival time was partitioned into three health states — toxicity before disease progression (TOX), time without symptoms or toxicity before disease progression (TWiST), and relapse (REL). Utilities for these health states were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in KN355. Q-TWiST was derived as the utility-weighted sum of the mean health state durations. Results: Patients randomised to pembrolizumab plus chemotherapy had 3.7 months greater Q-TWiST (relative gain of 18%; P = 0.003) compared to those randomised to chemotherapy at the median follow-up of 44 months, and 4.3 months greater Q-TWiST (relative gain of 20%; P = 0.004) at the maximum follow-up of 52 months. The Q-TWiST gain increased with longer follow-up time. Conclusions: Pembrolizumab plus chemotherapy was associated with statistically significant and clinically important improvement in Q-TWiST compared to chemotherapy in previously untreated PD-L1–positive mTNBC. Highlights: This Q-TWiST analysis assessed quality-adjusted survival in patients with mTNBC. Pembrolizumab showed a significant Q-TWiST benefit in PD-L1–positive mTNBC. The benefits continued to accrue with longer follow-up time. Pembrolizumab demonstrated a favourable benefit-risk profile in this population.