Dr Shah on 5-Year Outcomes With Pembrolizumab/Chemo in Esophageal Cancer

Manish A. Shah, MD, director, Gastrointestinal Oncology Program, Weill Cornell Medicine; chief, Solid Tumor Service, co-director, Center for Advanced Digestive Disease, NewYork Presbyterian, discusses 5-year outcomes from the phase 3 KEYNOTE-590 trial (NCT03189719) of frontline pembrolizumab (Keytruda) plus chemotherapy in patients with esophageal cancer, as well as potential future directions with immunotherapy in the management of this disease.

In this trial, at a median time from random assignment to the data cutoff of 58.8 months (range, 49.2-70.6), the median overall survival (OS) in the intent-to-treat population was 12.3 months (95% CI, 10.5-14.0) in the pembrolizumab arm vs 9.8 months (95% CI, 8.8-11.0) with placebo plus chemotherapy (HR, 0.72; 95% CI, 0.62-0.84). The 5-year OS rates were 10.6% and 3.0% in the pembrolizumab and placebo arms, respectively. The median progression-free survival (PFS) was 6.3 months (95% CI, 6.2-7.1) with pembrolizumab vs 5.8 months (95% CI, 5.0-6.0) with placebo (HR, 0.64; 95% CI, 0.54-0.75), and the 5-year PFS rates in these arms were 5.5% and 0%, respectively.

The long-term OS and PFS benefits demonstrated with pembrolizumab plus chemotherapy in KEYNOTE-590 indicate that this combination should be used in patients with advanced esophageal cancer, Shah says. Importantly, this study showed that patients with typical evidence of metastatic disease, including liver metastases, tended to have the longest OS outcomes, Shah explains. The sustained efficacy of pembrolizumab plus chemotherapy, as well as its tolerable safety profile, support the incorporation of this combination as a standard-of-care regimen in esophageal cancer, Shah emphasizes.

Immunotherapy has advanced the treatment paradigm in several cancers, especially esophageal cancer, according to Shah. Going forward, biomarker testing will help determine whether esophageal cancer tumors express PD-L1, Shah notes. Patients with PD-L1–positive disease may receive pembrolizumab plus chemotherapy to experience maximum benefit from their treatment, Shah says. KEYNOTE-590 demonstrates that patients with esophageal cancer who receive this combination may live for approximately 5 years, an outcome that was previously not observed in this disease, Shah concludes.