FORMAL DISCUSSANT of the KEYNOTE-189 trial, Roy S. Herbst, MD, PhD, Chief of Medical Oncology at Smilow Cancer Hospital, Yale Cancer Center, New Haven, heartily endorsed the new triplet combination of pembrolizumab, pemetrexed, and a platinum in advanced nonsquamous non– small cell lung cancer (NSCLC). 

Roy S. Herbst, MD, PhD

“The answer to the question about whether these results will change the standard of care for untreated NSCLC is an absolute ‘Yes,’” he said. “This randomized phase III trial sets a new standard.” 

Dr. Herbst added: “The results of this trial quite frankly exceeded expectations. The study showed extraordinary rates of overall survival, progression-free survival, and objective response,” he continued. The pembrolizumab (Keytruda) combination improved survival among all subgroups and was well tolerated, he noted. 

“I also believe we should still use programmed cell death ligand 1 (PD-L1) for patient selection. Other biomarkers will be studied. Remember, only 34% of patients are still progression-free at 1 year. We must continue our search for better biomarkers,” he continued. The field of biomarkers is evolving, with tumor mutation burden emerging as a distinct independent biomarker from PD-L1 expression, he said. 

Next Steps 

DR. HERBST did inject a note of caution about long-term adverse events with the triplet combination. “We might have to wait for longer-term data to truly understand the effects of chemotherapy combined with immunotherapy,” he noted. 

The ongoing INSIGNA trial is designed to shed further light on combinations of immunotherapy plus chemotherapy. That study (a joint effort between SWOG and ECOG) is enrolling patients with PD-L1 tumor proportion scores ≥ 1% and randomizing them to one of three arms: pembrolizumab as first-line treatment followed by second-line carboplatin/pemetrexed (Alimta); first-line pembrolizumab followed by second-line pembrolizumab, carboplatin, and pemetrexed; and the triplet followed by pemetrexed/pembrolizumab maintenance with no specified second-line therapy. 

Next steps will include evaluating the immunotherapy/chemotherapy combination earlier in the course of disease in the adjuvant setting and exploring the activity of the triplet in squamous NSCLC, small cell lung cancer, and oncogene-driven tumors (ie, epidermal growth factor receptor [EGFR] and anaplastic lymphoma kinase [ALK] rearrangements). 

“Future studies will evaluate new combinations, with or without chemotherapy, so we can further personalize immunotherapy,” Dr. Herbst stated. “We are in a truly exciting time, as we work to personalize immunotherapy to benefit more patients.” ■

DISCLOSURE: Dr. Herbst has received research support from AstraZeneca, Eli Lilly, and Merck and has served as a consultant for AstraZeneca, Eli Lilly, Genentech/Roche, Merck, NextCure, and Pfizer.