Invited discussant of the NeoCOAST trial, Edward B. Garon, MD, Professor of Medicine and Director of the Thoracic Oncology Program at David Geffen School of Medicine at the University of California Los Angeles, praised the study: “NeoCOAST is an impressive study that showed numerical benefit when three separate novel agents were added to durvalumab. The observations about biomarkers are limited by a lack of adequate tissue samples, making the analyses mainly exploratory.”

Dr. Garon continued: “In this four-arm study, patients were randomly assigned to receive durvalumab or durvalumab plus one of three novel agents. The study arms were numerically superior to durvalumab. Studies like this are becoming the rage in NSCLC,” he added.

Edward B. Garon, MD

Study Advantages and Limitations

This type of study has some advantages over conventional studies. “The number of patients in the control arm is limited, and the design allows the evaluation of multiple agents with smaller numbers of patients. You can add an additional arm if desired,” Dr. Garon said. “The disadvantage is that we are highly dependent on the proportionally small control arm for interpretation. Also, the trial can become unwieldy or complicated by an individual arm, which slows down the entire study.”

Furthermore, Dr. Garon, noted another challenge. “It will be difficult to recruit patients to the next trial, NeoCOAST-2, because we now have an approved combination in this space—nivolumab plus chemotherapy.”

Questions linger about NeoCOAST, according to Dr. Garon. “It is possible that some of these patients may have been cured by surgery alone. It is not clear whether this is ‘enough’ immunotherapy. The clinical value of pathologic endpoints, particularly major pathologic response, is unproven,” he said. “Also, I would argue that the control arm did underperform, whereas the combination arms did a little better than historical controls.”

Regarding the exploratory biomarker analysis, Dr. Garon commented: “There are limitations in the tissue evaluation. Only a handful of patients have evaluable samples. When there are so few data points, the most aberrant data points drive the correlation.”

DISCLOSURE: Dr. Garon has served as a consultant or advisor to ABL Bio, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceutical, Eisai, EMD Serono, Eli Lilly, GlaxoSmithKline, Gilead, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio Therapeutics; and has received institutional research funding from ABL Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis.