Four-year outcomes with perioperative toripalimab plus chemotherapy in resectable stage III non-small cell lung cancer (NeoTAP01 study)

Background: The previously reported primary analyses of NeoTAP01 trial demonstrated encouraging effectiveness and safety of perioperative toripalimab plus chemotherapy in resectable stage III non-small cell lung cancer (NSCLC). We now present the 4-year follow-up outcomes in order to confirm the stability of its benefits. Methods: This trial enrolled 33 NSCLC patients with resectable IIIA and IIIB to receive three cycles of neoadjuvant toripalimab plus chemotherapy before surgery. Adjuvant toripalimab was suggested to conduct for 12 cycles postoperatively. With a median follow-up of 4.3 years, long-term outcomes, including event-free survival (EFS), overall survival (OS), and treatment-related adverse effects (TRAEs) were reported. Post hoc analyses explored the risk factors of recurrence in the level of pathologic and genomic characteristics. Results: In the per-protocol (PP) population, 4-year EFS and OS rates were 66.7% and 83.3%, respectively. The presence of pathologic complete response (pCR) trended toward favorable EFS [4-year EFS, 92.9% vs. 46.7%; hazard ratio (HR), 0.09; 95% confidence interval (CI): 0.01 to 0.76]. All the patients with recurrence in the non-pCR subgroup had received adjuvant treatment, and 75% of them experienced recurrence in less than 1 year after surgery. For the TRAEs, grade 3 pneumonitis happened in 11.1% (3/27) patients during the adjuvant therapy. STK11 and KEAP1 mutations were not associated with long-term survival risks. Conclusions: The 4-year clinical outcomes for perioperative toripalimab plus chemotherapy in resectable stage III NSCLC showed a sustained improvement in long-term EFS and OS. However, the effectiveness of adjuvant immunotherapy are still unclear, as definitive conclusions are limited by cohort size.