Bristol Myers Squibb announced that the U.S. Food and Drug Administration (FDA) approved Opdivo (nivolumab) for the treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by single-agent Opdivo as adjuvant treatment after surgery – otherwise referred to as perioperative therapy, which is used before and after surgery. The approval is based on results from the CheckMate-77T trial, the company’s second positive Phase 3 randomized trial with an immunotherapy-based combination for the treatment of resectable NSCLC. Opdivo is now the only PD-1 inhibitor to demonstrate statistically significant and clinically meaningful benefits in this disease versus chemotherapy in both a neoadjuvant-only regimen and as part of a perioperative regimen.
“Given the rates of disease recurrence in patients with resectable NSCLC, there is a clear need for options that can be administered before and after surgery that may target micrometastasis, help reduce the risk of cancer returning and improve the chance of successful surgical treatment,” said Tina Cascone, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “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.”
The CheckMate-77T trial evaluated the perioperative regimen of neoadjuvant Opdivo with platinum-doublet chemotherapy followed by surgery and adjuvant Opdivo monotherapy (n=229), compared to neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo (n=232) in adult patients with resectable NSCLC. In the trial, the Opdivo arm improved EFS, a primary endpoint, compared to the chemotherapy and placebo treatment arm. A high pCR rate was also observed as one of the pre-specified secondary endpoints.
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 in the Opdivo arm, compared to the chemotherapy and placebo arm, with a median follow-up of 25.4 months. In addition, 18-month EFS was demonstrated in 70% of patients in the Opdivo arm, compared to 50% of patients in the chemotherapy and placebo arm. Furthermore, 25% of patients in the Opdivo arm achieved pCR, while 4.7% of patients in the comparator arm achieved pCR in the intent-to-treat population (estimated treatment difference of 20.5%; 95% CI,14.3 to 26.6).
Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis and renal dysfunction; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity. 1 Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue and dexamethasone is not recommended outside of controlled clinical trials. Please see Important Safety Information below.
“This milestone expands the role of Opdivo -based treatments and builds upon the foundation set by the FDA approval of neoadjuvant-only Opdivo plus chemotherapy in resectable NSCLC based on the CheckMate-816 trial,” said Wendy Short Bartie, senior vice president of U.S. Oncology and Hematology at Bristol Myers Squibb. “With this new Opdivo -based regimen, we are reinforcing our commitment to helping improve patient outcomes and expanding our thoracic portfolio in early-stage disease.”
The recommended dose for Opdivo 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 Opdivo 480 mg every four weeks after surgery for up to 13 cycles (approximately one year) or until disease recurrence or unacceptable toxicity. The FDA previously approved Opdivo for adult patients with resectable (tumors ≥4 cm or node positive) NSCLC in the neoadjuvant setting, in combination with platinum-doublet chemotherapy. Opdivo and Opdivo -based combinations have been approved by the FDA in the neoadjuvant, adjuvant or perioperative settings across four cancers to date, including lung cancer, melanoma, bladder cancer and esophageal/gastroesophageal junction cancer.