Tina Cascone, MD, PhD
Discussant of the Neotorch study abstract, Tina Cascone, MD, PhD, of the Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, commended the authors for completing the initial analysis of the phase III randomized Neotorch trial, which demonstrated event-free survival improvement with perioperative chemotherapy plus toripalimab vs chemotherapy alone in patients with resectable, stage III, non–small cell lung cancer (NSCLC). Dr. Cascone noted that the higher major pathologic response and pathologic complete response rates in the combination arm were overall comparable to those seen in the CheckMate 816 and AEGEAN studies.1,2 Although encouraging overall survival results were observed in favor of the combination arm, Dr. Cascone emphasized the need for more mature data.
Number and Schedule of Chemoimmunotherapy: More to Learn
Dr. Cascone also highlighted the importance of the number and schedule of chemoimmunotherapy in the neoadjuvant setting, as there is currently “no consensus on the optimal number of cycles and sequence of cycles of chemoimmunotherapy.” She mentioned the neoSCORE trial, which demonstrated a higher major pathologic response rate with three cycles of neoadjuvant sintilimab plus chemotherapy compared with two cycles.3 The Neotorch and AEGEAN trials are both phase III randomized studies testing four cycles of chemoimmunotherapy, said Dr. Cascone, but their different perioperative schedules might impact long-term survival outcomes.
Dr. Cascone further discussed the significance of the perioperative chemoimmunotherapy approach in the Neotorch trial. She suggested that when given with one cycle postoperatively in patients with stage III disease, this strategy might be effective at eliminating micrometastatic disease in this subgroup of patients with a poorer prognosis.
“The administration of perioperative chemoimmunotherapy may be even more beneficial by providing continuous treatment throughout the surgical setting, enhancing micrometastatic killing and antitumor immunity and resulting in improved long-term outcomes,” she added.
Words of Caution
Despite the promising results, however, Dr. Cascone urged caution in interpreting the treatment-emergent adverse events and toxicity profiles, as numerically higher rates of grade 3 to 5 events were noted with the perioperative approach in the Neotorch trial compared with the CheckMate 816 trial. She also emphasized the need for event-free survival rates by pathologic complete response status and the percentage of residual viable tumor to guide therapy and minimize clinical and financial toxicities.
Finally, Dr. Cascone acknowledged that although cross-trial comparisons are not ideal, they will continue as the perioperative treatment landscape for resectable NSCLC continues to evolve.
“Forthcoming outcomes in stage II disease will help to refine optimal perioperative treatment strategies for subgroups of patients with NSCLC,” Dr. Cascone concluded.
DISCLOSURE: Dr. Cascone reported financial relationships with the Society for Immunotherapy of Cancer Care, Roche, Bristol Myers Squibb, Medscape, PeerView, IDEOlogy Health, OncLive, Mark Foundation for Cancer Research, MedImmune/AstraZeneca, Genentech, EMD Serono, Merck, Arrowhead Pharmaceuticals, Regeneron, Parker Institute for Cancer Immunotherapy, International Association for the Study of Lung Cancer, and DAVA Oncology.
REFERENCES
1. Forde PM, Spicer J, Lu S, et al: Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med 386:1973-1985, 2022.
2. Heymach JV, Mitsudomi T, Harpole D, et al: Design and rationale for a phase III, double-blind, placebo-controlled study of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab for the treatment of patients with resectable stages II and III non-small-cell lung cancer: The AEGEAN trial. Clin Lung Cancer 23:e247-e251, 2022.
3, Qiu F, Fan J, Shao M, et al: Two cycles versus three cycles of neoadjuvant sintilimab plus platinum-doublet chemotherapy in patients with resectable non-small-cell lung cancer (neoSCORE): A randomized, single center, two-arm phase II trial. 2022 ASCO Annual Meeting. Abstract 8500.
