Squamous Cell Frontline Therapy: IMpower 131, KEYNOTE-407

Neal E. Ready, MD, PhD: For squamous cell cancers, squamous cell lung cancers, we don't have any actionable alterations to allow oral therapy. Typically, the biomarker that we would test outside of a clinical trial would be for PD-L1. If the PD-L1 is high, then it would be reasonable to treat with pembrolizumab alone. When the tumor is inflamed, with high PD-L1 scores 70, 80, 90, 100%, single agent immunotherapy can be effective with minimal toxicity.

For the rest of the patients, initiating combination therapy is indicative. KEYNOTE-407 was a large randomized phase 3 trial that compared standard histology-based chemotherapy with or without pembrolizumab. It showed that the chemo I/O combination was superior to chemotherapy alone with a modest increase in toxicity, and certainly an important new standard of care.

In that same squamous cell population, we now have the CheckMate 227 regimen of nivolumab and low-dose ipilimumab, and also the CheckMate 9LA where we have an FDA approval for 2 cycles of chemotherapy plus nivolumab and ipilimumab.

In summary, for this metastatic squamous cell population that doesn't have active autoimmune diseases or some other contraindication or immunotherapy, it would be consideration of single-agent immunotherapy for the inflamed tumors with a high PD-L1 score, and then some type of combination therapy, either standard chemotherapy plus immunotherapy or nivolumab, ipilimumab with or without 2 cycles of initial chemotherapy, depending on the clinical circumstances and the preference of the patient.

Transcript Edited for Clarity