Dr Shah on the 5-Year Survival Outcomes From the KEYNOTE-590 Study in Esophageal Cancer

Manish A. Shah, MD, professor, medicine, Bartlett Family Professor in Gastrointestinal Oncology, Medicine, Weill Cornell Medical College, discusses the 5-year outcomes from the phase 3 KEYNOTE-590 study (NCT03189719) of first-line pembrolizumab (Keytruda) plus chemotherapy in patients with advanced esophageal cancer.

The KEYNOTE-590 study marked a shift in the approach to esophageal cancer management by combining chemotherapy with pembrolizumab immunotherapy, Shah begins. Initial results, revealed after a median follow-up of 22.6 months, indicated an overall survival (OS) advantage for patients receiving pembrolizumab plus chemotherapy compared with chemotherapy alone, he explains. Notably, at the 2022 Gastrointestinal Cancers symposium, investigators presented updated findings from the study, which revealed that first-line pembrolizumab given with chemotherapy maintained a clinically significant OS benefit in patients with locally advanced and metastatic esophageal cancer.

The latest update, presented during the 2024 Gastrointestinal Cancers Symposium, included the 5-year results from this trial, which randomly assigned 749 patients into groups receiving chemotherapy plus placebo or chemotherapy plus pembrolizumab, Shah elucidates.

The study encompassed both squamous cell and adenocarcinoma subtypes of esophageal cancer, examining various patient subgroups based on PD-L1 combined positive scores, he expands. Over the 5-year duration, the addition of pembrolizumab to chemotherapy consistently demonstrated a significant OS benefit compared with chemotherapy alone, Shah emphasizes. The 5-year OS rates with pembrolizumab ranged from 11.8% to 13.8%, depending on the subgroup, in contrast to a range of 3.4% to 3.8% with chemotherapy alone. This approximate quadrupling of the 5-year OS rates underscores the impact of pembrolizumab in enhancing outcomes, Shah imparts.

Furthermore, although the immune activation induced with immunotherapy can lead to adverse effects, the long-term OS data revealed a manageable rate of grade 3 to 5 immune-related toxicity and infusion reactions of 7.0% with pembrolizumab, he continues. In comparison, the rate of grade 3 to 5 immune-related toxicity and infusion reactions with chemotherapy alone was 2.2%. The minimal increase in toxicity, coupled with the substantial OS benefits, underscores the advantage of adding pembrolizumab to chemotherapy in patients with esophageal cancer, Shah concludes.