Findings from a phase III, randomized trial highlight the benefit derived from perioperative immunotherapy in patients with early-stage resectable non–small cell lung cancer (NSCLC), according to data presented during the ASCO Plenary Series: April 2023 Session.¹

Interim analysis of the Neotorch study showed a significant improvement in event-free survival for patients with resectable stage III (American Joint Committee on Cancer, 8th edition) NSCLC who were treated with toripalimab, a monoclonal antibody targeting the immune checkpoint PD-1, in combination with perioperative chemotherapy vs chemotherapy alone. Overall, the combination therapy had a manageable safety profile. At the data cutoff of November 30, 2022, the 2-year event-free survival rate was 64.7% in patients treated in the toripalimab arm compared with 38.7% in those who received chemotherapy alone. Median event-free survival was not reached at the time of data cutoff in the toripalimab cohort, but it was 15.1 months in patients who received chemotherapy alone.

“Toripalimab in combination with chemotherapy also demonstrated higher major pathologic response and pathologic complete response rates per blinded independent pathologic review, with overall survival results showing a trend favoring toripalimab,” said Shun Lu, MD, PhD, lead author of the study and Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital within Shanghai Jiaotong University, China. “Further research and long-term follow-up will be necessary to fully assess the impact of toripalimab on overall survival and to optimize treatment strategies for patients with early-stage NSCLC.”

Shun Lu, MD, PhD

As Dr. Lu explained, NSCLC is a leading cause of cancer-related deaths worldwide, and despite advances in treatment, there remains a need for more effective therapies, particularly in early-stage disease. Immunotherapy, such as toripalimab, has shown promise in treating various stages of NSCLC and may potentially improve survival outcomes in patients with early-stage disease, he said.

Study Methods

Neotorch is a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance vs chemotherapy alone in patients with resectable stage II or III NSCLC. The primary endpoints were event-free survival by investigator and major pathologic response rate by a blinded independent pathologic review in the stage III and stage II and III populations.

The interim analysis included 404 patients with stage III -NSCLC who were randomly assigned to receive either toripalimab (n = 202) or placebo (n = 202) combined with perioperative chemotherapy with three cycles given in the neoadjuvant -setting and one cycle administered in the adjuvant setting followed by maintenance toripalimab or placebo for up to 13 cycles.

Key Outcomes and Toxicity

With a median follow-up of 18.25 months, interim analysis from the Neotorch trial showed a significant improvement in event-free survival for patients treated with toripalimab (hazard ratio [HR] = 0.40; 95% confidence interval [CI] = 0.277–0.565; P < .0001). The median event-free survival was not reached in the toripalimab arm and was 15.1 months in the placebo arm.

According to Dr. Lu, a consistent effect on event-free survival, favoring toripalimab, was observed in all subgroups, including disease stage, PD-L1 expression, pathologic type, age groups, and Eastern Cooperative Oncology Group status.

“Patients achieved benefit from toripalimab regardless of PD-L1 expression,” said Dr. Lu. He noted that for patients with at least 1% PD-L1 expression on tumor cells, median event-free survival was not reached with toripalimab vs 13.3 months with chemotherapy alone. For patients with less than 1% PD-L1 expression, event-free survival was not reached with toripalimab vs 15.3 months with chemotherapy alone.

In combination with perioperative chemotherapy, toripalimab demonstrated higher major pathologic response and pathologic complete response rates per blinded independent pathologic review, at 48.5% vs 8.4% and 24.8% vs 1.0%, respectively. The overall survival results also showed a trend favoring toripalimab (HR = 0.62, P = .0502).

Finally, the safety profile of toripalimab was reported to be manageable, with no new safety signals identified, according to Dr. Lu. The incidence of grade 3 or higher adverse events was comparable between the toripalimab and placebo arms (63.4% vs 54.0%). However, the incidence of immune-related adverse events was more frequent with toripalimab (42.1% vs 22.8%).

Event-free survival, major pathologic response, and overall survival in patients with stage II or III NSCLC will be statistically tested in hierarchy at the final analysis. 

DISCLOSURE: The Neotorch study was funded by Shanghai Junshi Biosciences Co., Ltd. Dr. Lu reported financial relationships with AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Pfizer, Prime Oncology, Roche, Simcere, Yuhan, Zai Lab, Hansoh Pharma, and Hengrui Therapeutics.

REFERENCE

1. Lu S, Wu L, Zhang W, et al: Perioperative toripalimab + platinum-doublet chemotherapy vs chemotherapy in resectable stage II/III non-small cell lung cancer: Interim event-free survival analysis of the phase III Neotorch study. ASCO Plenary Series. Abstract 425126. Presented April 20, 2023.