FDA Approves Perioperative Nivolumab for Resectable NSCLC Without EGFR or ALK Mutations
Key Insights
The FDA approved nivolumab with platinum-doublet chemotherapy as neoadjuvant treatment, followed by nivolumab as adjuvant treatment for resectable NSCLC.
The approval is specifically for patients without EGFR (search) mutations or ALK (search) rearrangements, based on the CheckMate-77T trial results.
The Opdivo regimen showed a 42% reduction in the risk of disease recurrence, progression, or death compared to chemotherapy and placebo.
The FDA has granted approval to nivolumab (Opdivo) in combination with platinum-doublet chemotherapy as a neoadjuvant treatment, followed by single-agent nivolumab as adjuvant therapy, for adult patients with resectable non-small cell lung cancer (search) (NSCLC) without known epidermal growth factor receptor (EGFR (search)) mutations or anaplastic lymphoma kinase (ALK (search)) rearrangements. This decision, announced on October 3, 2024, marks a significant advancement in the treatment landscape for resectable NSCLC, offering a new perioperative option for patients. The approval is based on the CheckMate-77T trial, highlighting the potential of this regimen to improve event-free survival and pathological response rates.
CheckMate-77T Trial Results
The approval is based on data from the Phase 3 CheckMate-77T trial, which evaluated the perioperative regimen of neoadjuvant nivolumab with platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab monotherapy, compared to neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo. The trial included 461 adult patients with resectable NSCLC.
The results demonstrated a statistically significant improvement in event-free survival (EFS) in the nivolumab arm compared to the chemotherapy and placebo arm. The risk of disease recurrence, progression, or death was reduced by 42% (EFS Hazard Ratio [HR] 0.58; 95% Confidence Interval [CI]: 0.43 to 0.78; P = 0.00025) in patients treated with nivolumab, with a median follow-up of 25.4 months. Additionally, 18-month EFS was demonstrated in 70% of patients in the nivolumab arm, compared to 50% in the chemotherapy and placebo arm. Furthermore, 25% of patients in the nivolumab arm achieved pathological complete response (pCR), while 4.7% of patients in the comparator arm achieved pCR.
Safety and Efficacy
The most common adverse reactions (reported in ≥20%) in patients receiving nivolumab in combination with chemotherapy were anemia (39.5%), constipation (32.0%), nausea (28.9%), fatigue (28.1%), alopecia (25.9%), and cough (21.9%). Serious adverse reactions occurred in 21% of patients who received nivolumab in combination with platinum-doublet chemotherapy as neoadjuvant treatment. Fatal adverse reactions occurred in 2.2% of patients.
Tina Cascone, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, noted, "This approval is a step forward for patients with resectable disease, as the perioperative nivolumab plus neoadjuvant chemotherapy regimen can offer an improved event free survival (EFS) compared with neoadjuvant chemotherapy alone and has the potential for achieving a pathologic response (pCR) in one in four patients."
Dosing and Administration
The recommended dose for nivolumab in this indication is 360 mg with platinum-doublet chemotherapy on the same day every three weeks for up to four cycles or until disease progression or unacceptable toxicity, then continued as a single-agent nivolumab 480 mg every four weeks after surgery for up to 13 cycles (approximately one year) or until disease recurrence or unacceptable toxicity.
Impact on NSCLC Treatment
This approval expands the role of nivolumab-based treatments and builds upon the foundation set by the FDA approval of neoadjuvant-only nivolumab plus chemotherapy in resectable NSCLC based on the CheckMate-816 trial. With this new nivolumab-based regimen, Bristol Myers Squibb (search) is reinforcing its commitment to helping improve patient outcomes and expanding its thoracic portfolio in early-stage disease.