Practical Considerations for Adjuvant vs. Neoadjuvant Immunotherapy in NSCLC

Justin Gainor, MD, director of targeted immunotherapy and assistant professor of medicine at Harvard Medical School, discusses some of the factors clinicians should consider when deciding between neoadjuvant and adjuvant immunotherapy in patients with lung cancer.

Transcription

When deciding between neoadjuvant and adjuvant therapy, there are several factors one can consider. Some of them are practical. Some of them are biological.

On the practical side, with naoadjuvant studies, one can use efficacy endpoints at the time of resection. For example, one of the popular efficacy endpoints in neoadjuvant studies so far has been major pathologic response. Pathologic response as an endpoint is something that is pretty standard in breast cancer. In lung cancer, we really haven't used that as an endpoint. And that's partly because complete pathologic responses are quite uncommon in lung cancer. So that's led this major pathologic response, which is less than 10% of viable tumor cells. So you can design a study where patients get 2 and 4 doses of checkpoint inhibitors and then they go to resection. With a primary endpoint of major pathologic response, you're going to get that efficacy endpoint much sooner than, say, in the adjuvant setting where you're having patients undergo surgery and you're administering adjuvant checkpoint inhibitors and you're waiting for relapses as the endpoint. That can take much, much longer. So that's one of the practical considerations.

Another practical consideration is the biomarker question. For example, there's intense interest in trying to understand biomarkers of response to checkpoint inhibitors. One of the key avenues to understanding those mechanisms is tissue -- actually having tissue from the cancer and seeing are there specific genomic markers in the immune microenvironment. Are those predictors? So a neoadjuvant approach actually allows you to have both the pretreatment set of tissue, as well as a post-treatment to see how the tumor has changed in response to your therapy. I think that's one of the other reasons why there's been some enthusiasm for the neoadjuvant approach because it allows investigators to actually get more tissue.