Roy S. Herbst, MD, PhD

Invited discussant Roy S. Herbst, MD, PhD, Deputy Director of the Yale Cancer Center, New Haven, Connecticut, called this “a very exciting abstract exploring when surgery meets immunotherapy.”

He commented: “NSCLC is a big disease, affecting 2 million or more people worldwide, and this is the tip of the iceberg. About 20% to 25% of patients with NSCLC have driver mutations, and these people don’t respond well to checkpoint inhibitor therapy. Outcomes in NSCLC need to be improved. The 5-year recurrence rate in resectable NSCLC is about 45%. This means we have to bring our best therapies early,” he stated. “Adjuvant therapy has come of age,” he continued. “Atezolizumab [as studied in IMpower010] and pembrolizumab [in KEYNOTE-091] are used in the adjuvant setting, and nivolumab [in CheckMate 816] led to the first neoadjuvant approval of a checkpoint inhibitor in NSCLC,” Dr. Herbst explained.

AEGEAN and Beyond

“AEGEAN utilizes both perioperative and neoadjuvant therapies. It is a large trial and further confirms that immunotherapy is here to stay [for resectable NSCLC]. It is a positive trial…. This study establishes neoadjuvant and adjuvant durvalumab as a new standard of care…. It is the second large, randomized trial to demonstrate value of immunotherapy in the neoadjuvant setting. We need multimodality review, and we need to molecularly profile tumors before surgery. More information is necessary to decide which approach to take. There are several trials and lots of data, and we need further steps,” he said.

Dr. Herbst proposed a pragmatic, real-world trial with a diverse patient population to determine the value of adjuvant and neoadjuvant immunotherapy combinations. “Such a trial would compare neoadjuvant chemoimmunotherapy and surgical resection using multiple anti–PD-1 and anti–PD-L1 agents. It should be prospective, interventional, and randomized. We need to determine whether patients who achieve a pathologic complete response need more therapy and to investigate why some tumors are not sensitive to immunotherapy. Although we are now preventing tumors from metastasizing, more work needs to be done. We can work on it together,” he concluded. 

DISCLOSURE: Dr. Herbst has served on the advisory board of Immunocore and Junshi Biosciences; has received consulting fees from Junshi Biosciences, AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Cancel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, Dynamicure Biotechnology, eFFECTOR Therapeutics, Eli Lilly and Company, EMD Serono, Genentech, Gilead Sciences, HiberCell, I-Mab Biopharma, Immune-Onc Therapeutics, Immunocore, Janssen, Johnson and Johnson, Loxo Oncology, Merck and Company, Mirati Therapeutics, Nexcure, Novartis, Ocean Biomedical, Oncocyte Corp, Oncternal Therapeutics, Pfizer, Regeneron Pharmaceuticals, Revelar Biotherapeutics, Ribbon Therapeutics, Roche, Sanofi, and Xencor; and has received research funding from AstraZeneca, Eli Lilly and Company, Genentech/Roche, and Merck and Company.