Toripalimab/Chemo Improves EFS Vs Chemo Alone in Resectable NSCLC

Combination treatment with perioperative toripalimab (Tuoyi) and chemotherapy significantly improved event-free survival (EFS) over chemotherapy alone in patients with resectable stage III non–small cell lung cancer (NSCLC), according to findings from the phase 3 Neotorch study (NCT04158440) presented at an American Society of Clinical Oncology (ASCO) virtual plenary session.

"EFS [also] favored the toripalimab plus chemotherapy [arm] across the various key subgroups, including disease stage, PD-L1 expression status, pathologic type, different age groups, and ECOG status," according to an expert from Shanghai Lung Cancer Center.

With a median follow-up of 18.25 months, the median EFS as assessed by investigators was not evaluable (NE; 95% CI, 24.4-NE) for patients in the toripalimab plus chemotherapy arm vs 15.1 months (95% CI, 10.6-21.9) in the placebo plus chemotherapy arm (Hazard ratio [HR], 0.40; 95% CI, 0.277-0.565; two-sided P <.0001). The estimated 1-year EFS rates in the toripalimab and placebo arms, respectively, were 84.4% vs 57.0%. At 2 years, the estimated EFS rates were 64.7% and 38.7% in each respective arm.

In terms of EFS as assessed by independent review committee, the median EFS in the toripalimab arm was NE (95% CI, NE-NE) and 15.5 months (95% CI, 9.9-NE) in the placebo arm (HR, 0.40; 95% CI, 0.271-0.572; P <.0001). The 1-year and 2-year EFS rates in the toripalimab and placebo arms, respectively, were 80.7% vs 55.7% and 66.7% vs 46.1%.

“EFS [also] favored the toripalimab plus chemotherapy [arm] across the various key subgroups, including disease stage, PD-L1 expression status, pathologic type, different age groups, and ECOG status.” presenting author Shun Lu, MD, PhD, said in the presentation.

Lu is a professor and chief of Shanghai Lung Cancer Center, Shanghai Chest Hospital at Shanghai Jiao Tong University.

In patients with a PD-L1 expression status of 1% or higher (n = 265), the median EFS was NE in the toripalimab group vs 13.3 months in the placebo group (HR, 0.31; 95% CI, 0.197-0.481). In those with a PD-L1 expression status of less than 1% (n = 139), the median EFS was NE vs 15.3 months in each respective treatment arm (HR, 0.59; 95% CI, 0.327-1.034).

Investigators of the randomized, double-blind, placebo-controlled phase 3 Neotorch study assessed the safety and efficacy of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance compared with chemotherapy alone in patients with resectable stage II or III NSCLC. Patients were randomly assigned to receive 240 mg of neoadjuvant toripalimab or matched placebo plus platinum-based chemotherapy every 3 weeks for 3 cycles followed by adjuvant toripalimab or placebo plus chemotherapy every 3 weeks for 1 cycle, then maintenance toripalimab or placebo every 3 weeks for up to 13 cycles.

The primary end points were EFS by investigator assessment and major pathologic response (mPR) by blinded independent pathologic review. Secondary end points included overall survival (OS), pathologic complete response (pCR), disease-free survival, and safety and feasibility of surgery.

Those with newly diagnosed resectable stage II or III NSCLC and EGFR or ALK wild-type disease were eligible for enrollment on the study. Additional inclusion criteria included having biopsy tissue available for biomarker testing and evaluable lesions.

Investigators randomly assigned a total of 404 patients to treatment, with 202 receiving toripalimab plus chemotherapy and 202 receiving placebo plus chemotherapy.

Patients had a median age of 62 years (range, 29-70) and the majority of patients were male (91.6%). Additionally, most patients were former smokers (74.8%), had an ECOG performance status of 1 (64.6%), squamous histology (77.7%), and stage IIIA disease (67.3%).

The mPR was observed in 48.5% (95% CI, 41.4%-55.6%) in the toripalimab arm vs 8.4% (95% CI, 5.0%-13.1%) in the placebo arm (P <.0001).

The pCR as assessed by pathologist was 28.2% (95% CI, 22.1%-35.0%) in the toripalimab arm vs 1.0% (95% CI, 0.1%-3.5%) in the placebo arm (P <.0001). The pCR by blinded independent pathologic review was 24.8% (95% CI, 19.0%-31.3%) and 1.0% (95% CI, 0.1%-3.5%) in each respective arm (P <.0001).

The median OS was NE (95% CI, NE-NE) in the toripalimab arm and 30.4 months (95% CI, 29.2-NE) in the placebo arm (HR, 0.62; 95% CI, 0.381-0.999). The estimated 1-year and 2-year OS rates in each respective arm were 94.4% vs 89.6% and 81.2% vs 74.3%.

“OS will be formally tested at a final analysis,” Shun said.

Overall, 82.2% of patients in the toripalimab arm underwent surgery compared with 73.3% of patients in the placebo arm. The rate of R0 resection in each respective arm was 95.8% (95% CI, 91.5%-98.3%) vs 92.6% (95% CI, 87.1%-96.2%).

“The incidence of adverse effects [AEs] leading to the discontinuation of toripalimab or placebo and AEs leading to deaths were comparable between the 2 arms, which suggested that the toxicity can be effectively managed,” Shun said.

Shun indicated that no new safety signals were identified in the trial. Additionally, the incidence of surgery-related postoperative AEs was comparable between the toripalimab and placebo arms.

A total of 63.4% of those in the toripalimab arm 54.0% of those in the placebo arm developed grade 3 or higher treatment-emergent adverse effects (TEAEs). Moreover, 3.0% and 2.0% of patients in each respective arm died due to TEAEs.

Common any-grade TEAEs in the toripalimab and placebo arms, respectively included anemia, neutropenia, leukopenia, and cough. Additionally, frequent high-grade TEAEs included neutropenia, leukopenia, pneumonia, anemia, and thrombocytopenia.

Reference

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 (NSCLC): interim event-free survival (EFS) analysis of the phase III Neotorch study. J Clin Oncol. 2023;41(suppl 36; abstr 425126). doi:10.1200/JCO.2023.41.36_suppl.425126