The U.S. Food and Drug Administration (FDA) has granted approval for a perioperative treatment regimen involving neoadjuvant Opdivo (nivolumab) combined with chemotherapy, followed by surgery, and adjuvant single-agent Opdivo for patients with resectable non-small cell lung cancer (NSCLC). This decision was supported by the findings from the CheckMate-77T trial, which showed that the Opdivo-based regimen significantly improved event-free survival (EFS) compared to chemotherapy with a placebo. The trial also observed a notable pathologic complete response (pCR) rate.
Opdivo is now the only PD-1 inhibitor approved for resectable NSCLC both as a neoadjuvant therapy and as part of a perioperative regimen. This approval is a significant addition to Bristol Myers Squibb’s thoracic treatment portfolio, underscoring the company's commitment to advancing early-stage cancer therapies.
The FDA's approval applies to adult patients with resectable NSCLC (tumors ≥4 cm or node-positive) without known mutations in the epidermal growth factor receptor (EGFR) or rearrangements in anaplastic lymphoma kinase (ALK). The treatment involves using Opdivo in combination with platinum-doublet chemotherapy before surgery and continuing Opdivo as a single agent after surgery. This regimen, referred to as perioperative therapy, is designed to be administered before and after surgery.
In the CheckMate-77T trial, patients receiving the Opdivo regimen showed better outcomes than those treated with chemotherapy and placebo. The trial demonstrated a significant improvement in EFS, with a 42% reduction in the risk of disease recurrence, progression, or death. Additionally, patients in the Opdivo group achieved an 18-month EFS of 70%, compared to 50% in the placebo group. The pCR rate was also significantly higher in the Opdivo group, with 25% of patients achieving pCR, compared to 4.7% in the placebo group.
The recommended Opdivo dosage for this indication is 360 mg combined with platinum-doublet chemotherapy every three weeks for up to four cycles, followed by 480 mg of Opdivo as a single agent every four weeks after surgery, for up to 13 cycles or until disease progression or unacceptable toxicity occurs.
The safety profile of Opdivo in this perioperative setting was consistent with previous studies. However, patients may experience immune-mediated adverse reactions such as pneumonitis, colitis, and hepatitis. Severe complications like infusion reactions and embryo-fetal toxicity are also potential risks. Treatment is not recommended for patients with multiple myeloma receiving PD-1 or PD-L1 inhibitors combined with thalidomide analogues and dexamethasone outside clinical trials.
Opdivo, either alone or in combination, has been approved in various settings for multiple cancers, including lung cancer, melanoma, bladder cancer, and esophageal or gastroesophageal junction cancers.
The CheckMate-77T study was a large-scale, randomized, double-blind trial involving 461 patients with resectable NSCLC. Participants were given either neoadjuvant Opdivo with chemotherapy or chemotherapy with a placebo. After surgery, patients continued with either Opdivo or a placebo for up to a year. The primary endpoint was EFS, and secondary endpoints included pCR and major pathological response, both evaluated through independent reviews.
Adverse reactions in patients receiving Opdivo and chemotherapy included common issues like anemia, constipation, and nausea. Serious reactions occurred in 21% of patients, with pneumonia being the most frequent. In some cases, treatment-related complications led to surgery cancellations.
The trial's safety findings aligned with earlier Opdivo studies, with no new safety concerns identified.
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