Based on event-free survival and pathologic complete response results, the FDA approved nivolumab in combination with platinum-doublet chemotherapy in March 2022.
Results from the phase 3 CheckMate-816 trial have found that treatment with neoadjuvant nivolumab plus chemotherapy significantly improves event-free survival (EFS) in patients with resectable non-small cell lung cancer (NSCLC).
According to the study, 3 cycles of nivolumab prior to surgery reduced the risk of disease recurrence, progression, or death by 37% and showed an encouraging early trend in overall survival. These data from the CheckMate-816 trial mark the first positive phase 3 trial with an immunotherapy-based combination in the neoadjuvant setting of NSCLC. It is also the fourth nivolumab trial to demonstrate benefit in earlier cancer stages.
The trial had a minimum follow-up of 21 months, and researchers noted that the reduction in disease recurrence, progression, or death was found across randomized patients. In patients receiving the combination, median EFS was 31.6 months, compared to 20.8 months for patients treated with chemotherapy alone.
Furthermore, although the data are still immature and the analysis did not reach statistical significance, favorable early overall survival (OS) results were observed in the combination treatment arm. At 2 years, 83% of patients treated with neoadjuvant nivolumab and chemotherapy were alive, compared to 71% of patients treated with chemotherapy alone. OS will continue to be followed for upcoming analyses, according to the study.
“While resectable non-small cell lung cancer may be curable in some cases, patients face a high probability of recurrence after surgery, so we need effective systemic treatment options to interrupt this trajectory,” said Nicolar Girard, MD, PhD, investigator of the CheckMate-816 trial, in a press release. “The results from CheckMate-816 represent the first demonstration of clear and significant benefits with neoadjuvant immunotherapy-based treatment over chemotherapy alone for these patients, initially seen with increased pathologic complete response and now with improved event-free survival and a positive trend in overall survival.”
The safety profile in the study was consistent with previous reports, and no new safety signals were observed at the time of the EFS analysis. Rates of grade 3-4 treatment-related adverse events (AEs) were similar in the combination arm versus the chemotherapy alone arm, as were all causality surgery-related grade 3-4 AEs. With nivolumab in combination with chemotherapy, 83% of patients went on to receive surgery compared to 75% with chemotherapy.
“Surgery is still the cornerstone of cure for patients with non-small cell lung cancer,” said Jonathan Spicer, MD, PhD, an investigator in CheckMate-816, in the press release. “The fact that neoadjuvant nivolumab with chemotherapy enabled shorter, less invasive, and less extensive operations without increasing complications or adverse events is of tremendous importance to thoracic surgeons and their patients. These findings, combined with the improved survival outcomes, have the potential to completely change the way surgeons and oncologists collaborate in treating patients with resectable non-small cell lung cancer.”
Based on the EFS and pathologic complete response results from the trial, in March 2022 the FDA approved nivolumab in combination with platinum-doublet chemotherapy every 3 weeks for 3 cycles for adults with resectable NSCLC in the neoadjuvant setting.
“The data from CheckMate-816, including the positive early overall survival results, reinforce the importance of researching immunotherapy in earlier stages of disease, and we look forward to continuing to see if this science translates into tangible benefits for patients and their families,” said Abderrahim Oukessou, MD, vice president and thoracic cancers development lead at Bristol Myers Squibb, in the press release.
Neoadjuvant Opdivo (nivolumab) with Chemotherapy Significantly Improves Event-Free Survival in Patients with Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate-816 Trial. News release. Bristol Myers Squibb; April 11, 2022. Accessed April 13, 2022. https://news.bms.com/news/details/2022/Neoadjuvant-Opdivo-nivolumab-with-Chemotherapy-Significantly-Improves-Event-Free-Survival-in-Patients-with-Resectable-Non-Small-Cell-Lung-Cancer-in-Phase-3-CheckMate--816-Trial/default.aspx