John V. Heymach, MD, PhD
FORMAL DISCUSSANT of this trial, John V. Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, also was optimistic about these early findings. “This is a proof-of-concept study showing this approach is safe. Only modest activity was observed with standard [Response Evaluation Criteria in Solid Tumors], but impressive activity was seen based on major pathologic response rate. Virtually all patients had some evidence of tumor shrinkage, and there were no delays in surgery,” he said.
“Unfortunately, current approaches to adjuvant therapy do not work well in eliminating micrometastatic disease. You see only a 5% marginal gain in survival at 5 years, yet it is part of the standard treatment of non–small cell lung cancer (NSCLC),” Dr. Heymach continued. “The current abstract is a journey toward incorporating immunotherapy into the treatment of earlier-stage NSCLC.”
‘Tour de Force’
THE INVESTIGATORS used a novel, sensitive, specific technique invented by Dr. Pardoll and colleagues to identify functional antitumor T-cell responses called MANAFEST. “This work represents a tour de force and is the most important innovation in this study. This technology is a way to see which T cells become activated and which T-cell receptors are shared by tumor and peripheral blood. We still need improvements to better identify tumor-infiltrating lymphocytes and T-cell receptors with specific antitumor activity,” he noted.
“These improvements could become a foundation for future personalization of immunotherapy. If T-cell receptors could be identified, we could personalize adaptive T-cell therapy,” he added.
Many questions remain, but Dr. Heymach believes neoadjuvant immunotherapy may be a better approach than conventional neoadjuvant therapy. Preclinical studies suggest that programmed cell death protein 1 (PD-1) inhibition improves survival, and neoadjuvant seems to be better than adjuvant therapy. Many clinical studies now underway should answer the questions prompted by this study. ■
DISCLOSURE: Dr. Heymach reported no conflicts of interest.
