Integrating QoL Analysis With Efficacy Outcomes in the Pembrolizumab KN-590 Study in First-Line Esophageal Cancer

In this video, Prof Eric Van Cutsem, MD, PhD, Division Head of Digestive Oncology at University of Leuven (KUL) and University Hospital Gasthuisberg, Leuven, Belgium and founding chair of WCGIC, discusses new data in the treatment of first-line esopahgeal and gastroesophageal junction cancer patients with Dr Marc Diez Garcia from Vall d’Hebron University Hospital Institute of Oncology in Barcelona, Spain. 

The two oncologists review the Q-TWIST analysis of the phase 3 KEYNOTE-590 study of first line pembrolizumab plus chemotherapy. The KEYNOTE-590 study is the first phase 3 study to demonstrate statistically significant and clinically meaningful improvement in OS and an outstanding PFS in all randomized and CPS ≥ 10 patients with locally advanced, unresectable, or metastatic esophageal cancer or gastroesophageal junction adenocarcinoma. The KN-590 study included patients with both esopahgeal squamous cell carcinoma and adenocarcinoma histologies. Pembrolizumab on the basis of this study (KN-590) was approved by the European Medicines Agency (EMA) in July 2021 for first-line esophageal and GEJ patients with CPS≥10.

Q-TWIST analysis divided survival time into 3 health states: time with grade 3+ toxicity before disease progression or death (TOX), time without symptoms or grade 3+ toxicities before progression (TWIST), and time from disease progression to death (REL). In all patients at month 33, patients receiving pembrolizumab + chemotherapy had a 1.51 month (95% CI, 0.10-2.95) longer restricted mean time in TWiST (5.95 vs 4.44 months), 1.59 month (95% CI, 0.76-2.43) longer restricted mean time in TOX (3.71 vs 2.12 months), and a 0.01 month (95% CI, -1.93-1.85) shorter restricted mean time in REL (6.16 vs 6.18 months) versus chemotherapy. For the restricted mean Q-TWIST in all patients, the difference between the pembrolizumab + chemotherapy and chemotherapy arms favored the pembrolizumab + chemotherapy arm by 2.30 months (95% CI, 1.27-3.40; 10.89 vs 8.59 months) at month 33, representing a 18.1% relative Q-TWiST gain.

The study concludes that pembrolizumab + chemotherapy demonstrated clinically meaningful improvement in quality-adjusted survival based on Q-TWIST analyses compared with chemotherapy in patients with advanced esophageal cancer.