Perioperative Toripalimab + Chemo in Stage III Lung Cancer

Lung cancer: Lung cancerAdding toripalimab to perioperative chemotherapy improves event-free survival (EFS) for patients with Stage III resectable non-small cell lung cancer (NSCLC), according to an interim analysis of a randomized, double-blind, placebo-controlled Phase III trial. After a median follow-up of 18.3 months, median EFS was not reached in the toripalimab arm versus 15.1 months in the placebo arm. “A significant improvement in EFS was observed in the toripalimab arm over the placebo,” said lead author Shun Lu, MD, PhD, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital School of Medicine of Shanghai Jiao Tong University in China. “The HR was 0.40, representing a 60 percent risk reduction in disease progression, disease recurrence, or death.” Lu presented the results during the April 2023 American Society of Clinical Oncology (ASCO) virtual plenary session. In addition to improving EFS, toripalimab led to significantly higher rates of major pathologic response (MPR) (48.5% vs. 8.4% with placebo) and pathologic complete response (pCR) (24.8% vs. 1%), and a favorable trend in overall survival (OS), Lu noted. In this analysis of the Neotorch study, 404 patients with Stage III NSCLC in China were randomized to receive either the anti-PD-1 monoclonal antibody toripalimab or a placebo in combination with chemotherapy every 3 weeks for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab or placebo monotherapy every 3 weeks for 13 cycles. The chemotherapy backbone varied depending on histology of the cancer, with paclitaxel or docetaxel for squamous type disease, and pemetrexed plus platinum for non-squamous type disease. Participation in the study required that patients have EGFR/ALK wild-type, biopsy tissue available for biomarker analysis, measurable lesions, and an ECOG performance status of 1 or less. Patients' baseline characteristics were evenly distributed between the two arms. PD-L1 positivity rate was about 65 percent in both arms and squamous carcinomas were found in 77.7 percent of patients. Two patients had distant metastases at baseline. At the November 30, 2022, data cutoff, the median follow-up was 18.25 months and 144 EFS events were observed. The 1-year EFS rate was 84.4 percent in the toripalimab arm versus 15 percent in the placebo arm. The 2-year EFS was 64.7 percent in the toripalimab arm versus 38.7 percent in the placebo arm. “Patients had a benefit from the toripalimab arm regardless of the PD-L1 expression, while the improvement in the EFS was more predominant in the PD-L1-positive patients,” Lu explained. The hazard ratio was 0.31 for patients with a tumor cell PD-L1 expression more than 1 percent and was 0.59 for those with tumor cell PD-L1 expression lower than 1 percent or nothing available. While OS data are not mature, the median OS was not reached in the toripalimab arm, compared to 30.4 months in the placebo arm, with a hazard ratio of 0.62. After the neoadjuvant therapy, more patients from the toripalimab arm (166 patients) underwent surgery compared to the placebo arm (148 patients). The vast majority (95.8%) of these patients who had surgery achieved R0 resection, which was slightly higher than in the placebo arm. Regarding safety, the incidence of adverse events seemed higher in the toripalimab arm, including Grade 3 or higher adverse events (63.4% vs. 54.0% with placebo), immune-related adverse events (42.1% vs. 22.8%), serious adverse events (40.6% vs. 28.2%), fatal adverse events (0.5% vs. 0%), and adverse events that lead to drug discontinuation (9.4% vs 7.4%). In summary, Lu said: “The addition of toripalimab to chemotherapy provided superior EFS while maintaining a manageable safety profile. Toripalimab demonstrated a higher MPR and pCR, and the OS results show a favorable trend toward toripalimab. The safety profile of the treatment is manageable, and no new safety signal was detected.” In the final analysis, more endpoints will be statistically tested in Stage III or Stage II-III patients' increase in OS. Charu Aggarwal, MD, MPH, ASCO expert in lung cancer and the Leslye M. Heisler Associate Professor of Lung Cancer Excellence at the University of Pennsylvania Perelman School of Medicine, commented: “This study demonstrates a potential new paradigm of perioperative immunotherapy, building upon the current standard of care of neoadjuvant immunotherapy with chemotherapy prior to surgical resection in patients with surgically resectable Stage III non-small cell lung cancer.” Mark L. Fuerst is a contributing writer.