An interim analysis of the Neotorch study highlighted the potential of immunotherapy for the treatment of early-stage non–small cell lung cancer (NSCLC), according to data presented by Lu et al during the ASCO Plenary Series: April 2023 Session (Abstract 425126). The findings showed a significant improvement in event-free survival for patients with resectable stage III NSCLC when treated with the PD-1 inhibitor toripalimab in combination with perioperative chemotherapy vs chemotherapy alone, with a manageable safety profile.
At the data cutoff date of November 30, 2022, the 2-year event-free survival rate was 64.7% in the toripalimab arm compared to 38.7% with chemotherapy alone. Median event-free survival was not estimable at the time of the cutoff in the toripalimab cohort but was 15.1 months with patients who only received chemotherapy.
“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. “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.”
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 could potentially improve survival outcomes in early-stage patients, he said.
Neotorch Study Methods
The Neotorch study 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/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 the intention-to-treat 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 chemotherapy.
Trend Favoring Toripalimab
With a median follow-up of 18.3 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, who noted that for patients with PD-L1 expression ≥ 1% on tumor cells, median event-free survival was not reached in the toripalimab arm vs 13.3 months in the placebo arm.
For patients with PD-L1 expression < 1%, event-free survival was not reached with toripalimab and was 15.3 months with placebo.
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 manageable, with no new safety signals identified, said Dr. Lu. The incidence of grade ≥ 3 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 in the toripalimab arm (42.1% vs. 22.8%).
Event-free survival in patients with stage II/III disease, major pathologic response in patients with stage III and stage II/III disease, and overall survival in patients with stage III and stage II/III disease will be statistically tested in hierarchy at the final analysis.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
