Dr Shah on Responses With Pembrolizumab Plus Chemo By PD-1 Status in Esophageal Cancer

Manish A. Shah, MD, professor, medicine, Bartlett Family Professor in Gastrointestinal Oncology, Medicine, Weill Cornell Medical College, discusses how the addition of first-line pembrolizumab (Keytruda) to chemotherapy impacts immune responses in patients with advanced esophageal cancer according to their PD-L1 expression status.

Pembrolizumab, which is a PD-1 inhibitor, has shown efficacy in various cancers by activating the immune response against tumor cells, Shah states. Squamous cell cancer and esophageal adenocarcinoma are known to overexpress PD-1, making these potential targets for pembrolizumab therapy, Shah explains. By blocking the PD-1 pathway, pembrolizumab allows the immune system to mount an effective response against cancer cells, he says. The efficacy of pembrolizumab is often measured using the hazard ratio, which compares the relative benefit of adding pembrolizumab to standard chemotherapy vs chemotherapy alone, he details.

At the 2024 Gastrointestinal Cancers Symposium, 5-year results from the phase 3 KEYNOTE-590 study (NCT03189719) were presented, demonstrating a continued improvement in overall survival with the pembrolizumab regimen vs chemotherapy alone, and a manageable rate of grade 3 to 5 immune-related toxicity and infusion reactions of 7.0%. Depending on the patient subgroup, 5-year OS rates with pembrolizumab ranged from 11.8% to 13.8% with pembrolizumab plus chemotherapy vs a range of 3.4% to 3.8% with chemotherapy alone.

In patients with a combined positive score (CPS) of 10 or higher, the hazard ratio for overall survival (OS) was approximately 0.64, Shah states. This translates to a significant 36% improvement in survival with the addition of pembrolizumab to chemotherapy, he adds.

Even in patients with lower CPS scores, the benefit of pembrolizumab was still observed, although to a lesser extent compared with those who exhibit a higher CPS scores, Shah adds. This highlights the potential of pembrolizumab as a valuable addition to chemotherapy regimens for various cancers, particularly in those with higher PD-1 expression levels, he concludes.