FDA Approves Perioperative Opdivo and Chemotherapy for Resectable NSCLC

Bristol Myers Squibb announced that the U.S. FDA has approved Opdivo (nivolumab) for treating adults with resectable non-small cell lung cancer (NSCLC) with tumors ≥4 cm or node-positive, without known EGFR mutations or ALK rearrangements. This treatment includes a neoadjuvant regimen with platinum-doublet chemotherapy followed by adjuvant single-agent Opdivo post-surgery, termed perioperative therapy. This marks Opdivo as the sole approved PD-1 inhibitor for both neoadjuvant-only and perioperative treatment regimens for resectable NSCLC.

The FDA's approval is based on data from the CheckMate-77T trial, which demonstrated the superior efficacy of the Opdivo-based regimen over standard chemotherapy and placebo. The trial showed that patients receiving Opdivo had a significantly longer event-free survival (EFS) and a higher pathologic complete response (pCR) rate than those in the chemotherapy and placebo arm. Dr. Tina Cascone from the MD Anderson Cancer Center emphasized the importance of this approval, highlighting its potential to reduce disease recurrence and enhance surgical outcomes for patients with resectable NSCLC.

In the CheckMate-77T trial, 461 patients with resectable NSCLC were randomized to receive neoadjuvant Opdivo with platinum-doublet chemotherapy or a placebo combined with chemotherapy, followed by surgery and adjuvant Opdivo or placebo. The primary endpoint was EFS, evaluated by Blinded Independent Central Review (BICR). The Opdivo group showed a 42% reduction in the risk of recurrence, progression, or death compared to the chemotherapy and placebo group. Additionally, the 18-month EFS was 70% in the Opdivo group versus 50% in the comparator group. The pCR rate was notably higher in the Opdivo arm, with 25% of patients achieving pCR compared to 4.7% in the placebo group.

The safety profile of Opdivo includes severe and potentially fatal immune-mediated adverse reactions. Common adverse reactions in the neoadjuvant Opdivo with chemotherapy group included anemia, constipation, nausea, fatigue, alopecia, and cough. Serious adverse reactions were noted in 21% of patients, with pneumonia being the most frequent. Additionally, 2.2% of patients experienced fatal adverse reactions. In the adjuvant phase, serious adverse reactions occurred in 22% of patients, with pneumonitis/ILD being the most frequent.

Wendy Short Bartie of Bristol Myers Squibb highlighted that this milestone reinforces their commitment to improving patient outcomes and expanding their thoracic portfolio in early-stage disease. The recommended dosage for Opdivo in this indication is 360 mg with platinum-doublet chemotherapy every three weeks for up to four cycles, followed by single-agent Opdivo at 480 mg every four weeks for up to 13 cycles post-surgery.

This new approval builds on the prior FDA approval of neoadjuvant-only Opdivo plus chemotherapy for resectable NSCLC, based on the CheckMate-816 trial. Opdivo and its combinations have been approved by the FDA across various settings for multiple cancers, including lung cancer, melanoma, bladder cancer, and esophageal/gastroesophageal junction cancer.

The CheckMate-77T trial was a Phase 3, randomized, double-blind, multi-center study comparing neoadjuvant Opdivo combined with platinum-doublet chemotherapy followed by surgery and adjuvant Opdivo to a similar regimen with a placebo. The trial included 461 patients, split between the two treatment arms, analyzing endpoints such as EFS, pCR, and overall survival.

Lung cancer remains the leading cause of cancer-related deaths in the U.S., with NSCLC accounting for up to 85% of diagnoses. Despite surgery being a treatment option for non-metastatic early-stage NSCLC, recurrence rates range from 30% to 55%, underscoring the need for effective neoadjuvant and adjuvant therapies to improve long-term outcomes.

For treating multiple myeloma, it is recommended that patients avoid using a PD-1 or PD-L1 blocking antibody combined with a thalidomide analogue and dexamethasone outside controlled clinical trials.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!