On March 4, 2022, nivolumab was approved for use with platinum-doublet chemotherapy for resectable non–small cell lung cancer (NSCLC) in the neoadjuvant setting.1 The approval is the first for neoadjuvant therapy for early-stage NSCLC.
Supporting Efficacy Data
Approval was based on findings from the open-label CheckMate 816 trial (ClinicalTrials.gov identifier NCT02998528). A total of 358 patients with stage IB (≥ 4 cm), II, or IIIA NSCLC and measurable disease—enrolled regardless of tumor PD-L1 status—were randomly assigned to nivolumab at 360 mg and platinum-doublet chemotherapy every 3 weeks for up to three cycles (n = 179) or platinum-doublet chemotherapy on the same schedule (n = 179).
Platinum-doublet chemotherapy consisted of paclitaxel/carboplatin (any histology), pemetrexed/cisplatin (nonsquamous), or gemcitabine/cisplatin (squamous); patients in the chemotherapy group could also receive vinorelbine/cisplatin or docetaxel/cisplatin (any histology).
Nivolumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
On blinded independent central review, median event-free survival was 31.6 months (95% confidence interval [CI] = 30.2 months to not reached) in the nivolumab group vs 20.8 months (95% CI = 14.0–26.7 months) in the control group (hazard ratio = 0.63, 97.38% CI = 0.43–0.91, P = .0052). The pathologic complete response rate was 24% (95% CI = 18.0%–31.0%) vs 2.2% (95% CI = 0.6%–5.6%; P < .0001).
How It Is Used
The recommended dose of nivolumab is 360 mg, given before platinum-doublet chemotherapy on the same day every 3 weeks for three cycles. No dose reductions are recommended. Prescribing information provides instructions on dosage modifications for immune-mediated adverse reactions and infusion-related reactions.
In the checkmate 816 study, the most common adverse events of any grade in the nivolumab group were nausea (38% vs 45% in the control group), constipation (34% vs 32%), fatigue (26% vs 23%), decreased appetite (20% vs 23%), and rash (20% vs 7%). The most common grade 3 or adverse events included fatigue (2.3% vs 1.1%) and rash (2.3% vs 0%). The most common grade 3 or 4 laboratory abnormalities in the nivolumab group were neutropenia (22%) and lymphopenia (4.7%).
Serious adverse events occurred in 30% of the nivolumab group, most commonly (> 2%) pneumonia and vomiting. Adverse events led to discontinuation of treatment in 10%, most commonly due to anaphylactic reaction (1.7%) and acute kidney injury, rash, and fatigue (1.1% each). No fatal adverse events occurred.
The addition of nivolumab to chemotherapy did not result in more frequent delays or cancellations of surgery. Median lengths of hospital stay following definitive surgery and rates of adverse events identified as surgical complications were similar in both groups.
Nivolumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, and nephritis and renal dysfunction; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving nivolumab.
1. Opdivo (nivolumab) injection for intravenous use prescribing information, Bristol Myers Squibb, March 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/225554s112lbl.pdf. Accessed March 10, 2022.