For patients with resectable lung cancer, three major approaches can be used to reduce the risk of recurrence: Neoadjuvant, adjuvant, and, more recently, perioperative—which involves neoadjuvant therapy—then surgery, followed by adjuvant therapy. Data from head-to-head trials comparing neoadjuvant to perioperative immunotherapy are not yet available, so how can clinicians choose an optimal strategy for their patients?
During the first of two Presidential Symposia at the 2024 World Conference on Lung Cancer, Patrick Forde, MBBCh, a researcher at the Cork Cancer Research Center, University College Cork, Cork, Ireland, and formerly the Co-Director of the Division of Upper Aerodigestive Malignancies in the Department of Oncology at Johns Hopkins, presented findings from a comparison of patient-level data from two studies: CheckMate 77T and CheckMate 816.
CheckMate 77T evaluated perioperative nivolumab, with neoadjuvant nivolumab plus chemotherapy, followed by definitive surgery, then adjuvant nivolumab. CheckMate 816 assessed neoadjuvant-only nivolumab plus chemotherapy followed by surgical resection. Post-surgical therapy was left to the discretion of the investigators and could include optional chemotherapy with or without radiotherapy as adjuvant treatment.
“At present, nivolumab plus chemotherapy is the sole approved and guideline-recommended neoadjuvant immunotherapy-containing treatment for eligible patients with resectable NSCLC. The pathologic response rates across the two trials were similar,” Dr. Forde said. “A key clinical question that arises—now that we have these regimens available—is which patients derive benefit from perioperative nivolumab.”
In lieu of a direct comparison in a randomized trial, Dr. Forde and colleagues analyzed and compared patient-level data to find an answer.
The comparative analysis included patients from the CheckMate 816 study who completed surgery and those from 77T who completed at least one dose of nivolumab after surgery (adjuvant nivolumab). A total of 139 and 147 patients who received perioperative nivolumab and neoadjuvant-only chemo-immunotherapy were included in the analysis.
Describing the findings on the study endpoint—event-free survival (EFS), landmarked from the time of surgery—Dr. Forde said, “Perioperative nivolumab yielded an approximate 40% reduction in risk of recurrence or death after surgery.”
The hazard ratios for the comparison of the two approaches trended in favor of perioperative nivolumab in patients who achieved/did not achieve a pathological complete response. The same was true in patients with PD-L1–positive and PD-L1–negative tumors, although the improved EFS with perioperative nivolumab was more pronounced in PD-L1–negative patients. Dr. Forde noted that longer follow-up is needed in this subgroup. Perioperative nivolumab yielded better EFS rates in both stage IB-II and stage III NSCLC.
“In the near future, at least, we will not have a randomized controlled trial comparing these approaches to help us make clinical decisions,” Dr. Forde concluded. “This study represents the only comparison of perioperative versus neoadjuvant-only immunotherapy treatments for patients with resectable lung cancer. With the caveat that this is an exploratory analysis, these results may inform the potential benefit and clinical decisions in our day-to-day practice.”
Nan Wu, MD, Professor, Peking University Cancer Hospital & Institute, framed his discussion of Dr. Forde’s presentation and the preceding talk on the NeoCOAST-2 study, stating, “The immunotherapy paradigm in early-stage NSCLC has been evolving in two directions—one, from monotherapy to chemo-immunotherapy and immunotherapy-novel agent combinations and the other from adjuvant to neoadjuvant to perioperative.”
Dr. Wu pointed out a key unanswered question in the comparison of the CheckMate trials; Since both pathologic complete response and PD-L1 levels influence the survival benefit with neoadjuvant/perioperative chemo-immunotherapy, “in the future, we need to answer which one is a better prognostic marker for both treatment approaches.”
“Again, these are exploratory analyses, and they are one additional data point we use in the clinic, but I think this evidence is interesting,” Dr. Forde reiterated during the question-and-answer portion of the session.
