Dr. Patel on Immunotherapy Combinations in Lung Cancer

Jyoti D. Patel, MD, professor of medicine, director, Thoracic Oncology, University of Chicago Medicine, discusses immunotherapy combinations for patients with advanced nonsquamous non—small cell lung cancer.

In the absence of a driver mutation, immunotherapy can be given alone or in combination with chemotherapy, explains Patel. Patients with a PD-L1 tumor proportion score (TPS) ≥50% by immunohistochemistry could receive pembrolizumab (Keytruda) alone. For patients with a PD-L1 TPS <50%, the combination of chemotherapy and immunotherapy is recommended, according to Patel.

Data from the phase III KEYNOTE-189 trial established the combination of pembrolizumab, pemetrexed (Alimta), and platinum chemotherapy as a frontline standard of care in patients with metastatic nonsquamous NSCLC without EGFR or ALK alterations. The triplet regimen showed an improvement in response rates, progression-free survival, and overall survival (OS) versus placebo/chemotherapy. An updated analysis of the KEYNOTE-189 showed that the addition of pembrolizumab to chemotherapy demonstrated a 44% reduction in the risk of death versus chemotherapy alone (HR, 0.56; 95% CI, 0.45-0.70;&#8239;P&#8239;<.00001).

In the phase III IMpower150 trial, investigators evaluated carboplatin, paclitaxel, bevacizumab (Avastin), and atezolizumab (Tecentriq) in patients with metastatic nonsquamous NSCLC who had not received chemotherapy. There is scientific rationale for the combination of chemotherapy and immunotherapy, says Patel. The combination increases neoantigen presentation and results in a more favorable immune environment. The addition of bevacizumab inhibits the VEGF pathway, which improves dendritic cell function and leads to a synergistic benefit with the quadruplet therapy, concludes Patel.