Perioperative Toripalimab With Chemo Improves EFS in Resectable Stage III NSCLC

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The perioperative use of toripalimab with chemotherapy improved event-free survival (EFS) and reduced risk of disease recurrence, progression events, or death by 60% among patients with resectable stage III non–small cell lung cancer (NSCLC) vs chemotherapy alone, according to findings from the phase 3 Neotorch study (NCT04158440).¹

Findings presented at the ASCO April Plenary Series showed that among the 404 patients with stage lll NSCLC enrolled in the trial, at a median follow-up of 18.25 months, the interim EFS analysis showed a significant EFS improvement among patients treated with toripalimab (HR, 0.40; 95% Cl, 0.277-0.565; P < .0001). In the toripalimab arm, the median EFS was not reached (95% CI, 24.4 to not reached) compared with 15.1 months (95% CI, 10.6-21.9) in the placebo arm. Further, there was a consistent favorable effect on EFS in all subgroups with toripalimab, regardless of a patient's PD-L1 expression status.

The median overall survival (OS) was not reached in the toripalimab arm vs 30.4 months in the placebo arm (HR, 0.62). The OS will be formally tested at the final analysis. Additionally, the major pathological response (MPR) in the toripalimab arm were higher compared with the placebo arm (48.5% v 8.4%), as well as the pathologic complete response (pCR) rates per blinded independent pathologic review (24.8% v 1.0%; P < .0001), respectively.

"The treatments were overall well tolerated with no new safety signal identified in either treatment arm. The overall survival results demonstrated a trend favoring the toripalimab arm," Tina Cascone, MD, PhD, faculty, Graduate School of Biomedical Sciences, assistant professor, Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, told Targeted Oncology^TM.

“The Neotorch study has pioneered the world’s first ‘3+1+13’ perioperative treatment model for NSCLC, which incorporates immunotherapy into both preoperative neoadjuvant and postoperative adjuvant treatments,” said Shun Lu, PhD, Shanghai Chest Hospital, principal investigator of Neotorch, in a press release². “The study results show that the addition of toripalimab to chemotherapy provided a superior EFS in [patients with] stage III NSCLC than chemotherapy alone, while maintaining a manageable safety profile. We are hopeful that our innovative solution will further improve the effectiveness and accessibility of lung cancer treatments and medications and ignite a new torch of hope for patients.”

Neotorch is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of perioperative toripalimab in addition to chemotherapy, followed by toripalimab maintenance vs chemotherapy alone in patients with resectable stage II/III NSCLC.

"Toripalimab is a selective, recombinant, humanized monoclonal antibody that belongs to the group of immune checkpoint inhibitor drugs. Toripalimab blocks the interaction of PD-1 with its ligands and restores the anti-tumor immune response mediated by T cells," said Cascone.

The trial randomized patients with stage II/III resectable NSCLC who did not have EGFR/ALK alterations for non-squamous NSCLC in a 1:1 ratio to receive 240 mg toripalimab or placebo, combined with chemotherapy every 3 weeks (Q3W) for 3 cycles prior to surgery, and 1 cycle after surgery, which was followed by toripalimab or placebo alone Q3W for 13 cycles.

Those enrolled in the study were male and female patients aged 18 to 70 years with treatment-naïve disease that is histologically confirmed, measurable lesions, an ECOG performance status of 0-1, adequate organ function, and a good pulmonary function test.³

Primary end points of the study were EFS as assessed by the investigator and MPR rate as assessed by blinded independent pathologic review in the stage III and the intention-to-treat populations. Secondary end points consisted of OS, pCR rate, EFS as assessed by an independent review committee, and safety.

Between arms, the median age of patients was 62 (range, 29-70). Most patients were men (91.6%), former smokers (74.8%), and had squamous histology (77.7%). A total of 65.6% of patients had positive PD-L1 disease, and 67.3% had stage IIIA disease.¹ More patients from the toripalimab arm underwent surgery compared with in the placebo arm (82.2% v 73.3%). Additionally, 95.8% in the toripalimab group and 92.6% in the placebo group underwent surgery and achieved R0 resection, respectively.

"The combination of perioperative toripalimab plus chemotherapy followed by surgery and maintenance toripalimab crossed the prespecified trial efficacy boundary for significance and resulted in a 60% reduction [Hazard Ratio 0.40 [95% CI 0.277, 0.565]; two-sided P < .00010] in the risk of disease recurrence, progression, or death, with a median EFS not reached in the toripalimab arm vs 15.1 months in the placebo arm, with a median follow up time of 18.25 months. Benefit from toripalimab was noted in all subgroups, with very encouraging results in stage IIIB, squamous cell histology and regardless of tumor PD-L1 expression status. The investigators reported greater rates of major pathological response and pathological complete response per blinded independent pathologic review in the toripalimab arm vs the placebo arm [MPR rate: 48.5% vs 8.4% [nominal P< 0.0001]; pCR rate: 24.8% vs 1.0% [nominal P < 0.0001]]." said Cascone.

The Neotorch trial is the first phase 3 registered study to show EFS benefit of perioperative treatment with an anti-PD-1 monoclonal antibody for patients with resectable NSCLC.

"The Neotorch trial results are encouraging and build on the current standard of care of neoadjuvant chemoimmunotherapy for patients with resectable NSCLC and provide a framework for a perioperative treatment strategy that can benefit a high-risk population of patients with resectable NSCLC. The results of EFS, pathological responses and OS in stage II/III patients as part of the final analyses of the Neotorch trial are forthcoming. We are also looking forward to learning additional information from the subgroup analyses of Neotorch that will allow us to maximize the benefit of these therapies for our resectable patients with NSCLC," added Cascone.

REFERENCES:

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

2. Junshi Biosciences announces toripalimab plus chemotherapy significantly improved event-free survival (EFS) versus chemotherapy as perioperative treatment for resectable stage III non-small cell lung cancer (NSCLC) in phase 3 neotorch study. News release. Junshi Biosciences. April 20, 2023. Accessed April 21, 2023. https://yhoo.it/41rnwJR

3. Phase III study of toripalimab versus placebo plus chemotherapy in resectable NSCLC. ClinicalTrials.gov. Updated November 3, 2022. Accessed April 21, 2023. https://clinicaltrials.gov/ct2/show/NCT04158440