Neoadjuvant-Adjuvant Nivolumab Receives FDA Approval for Operable Lung Cancer

On October 3, 2024, the United States Food and Drug Administration (FDA) approved, with platinum-doublet chemotherapy as neoadjuvant treatment for adults with resectable non-small cell lung cancer (NSCLC; tumor ≥4 cm and/or node-positive), Opdivo, containing nivolumab, (Bristol Myers Squibb Company) immunotherapy. Approval also includes single-agent nivolumab as postoperative adjuvant treatment. This applies to patients without known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Immunotherapy Is Changing the Course of Lung Cancer

With 2.5 million new diagnoses annually worldwide, lung cancer remains both the most common cancer and the leading cause of cancer death. Non-small cell lung cancer (NSCLC) accounts for most cases. For resectable lung cancers, which can be completely removed surgically, both neoadjuvant (preoperative) and adjuvant (postoperative) treatments play a critical role in reducing recurrence risk. FDA approval of nivolumab is therefore an important step, particularly for patients eligible for surgery.

FDA Approval Based on CHECKMATE-77T

Approval is based on a large trial of nivolumab's efficacy and safety. The placebo-controlled, double-blind CHECKMATE-77T study included 461 patients with previously untreated, resectable NSCLC. Patients were randomized to nivolumab or placebo with platinum-based chemotherapy. Neoadjuvant treatment was given every three weeks for up to four cycles, followed after surgery by adjuvant single-agent nivolumab or placebo.

Primary Efficacy Endpoint: Event-Free Survival (EFS)

The primary efficacy endpoint was event-free survival (EFS), determined by blinded independent central review.

The results were striking:

• Median EFS had not been reached in the nivolumab group (95% CI: 28.9, NE), compared with 18.4 months in the placebo group (95% CI: 13.6, 28.1).
• This difference indicates that nivolumab with platinum-based chemotherapy delayed tumor recurrence and progression by 42% (HR 0.58 [95% CI: 0.43, 0.78]; p-value 0.00025).
• At a median follow-up of 25.4 months, disease-free survival was 70.2% with nivolumab and 50% with chemotherapy alone.

Overall Survival (OS)

Although overall survival (OS) had not yet been tested for statistical significance in the prespecified interim analysis, descriptive analysis showed no adverse effect with nivolumab. Longer-term survival data may therefore provide further insights.

Safety and Adverse Effects

Adverse effects with nivolumab plus chemotherapy were consistent with previous studies. During neoadjuvant treatment, adverse effects prevented surgery in 5.3% of nivolumab recipients and 3.5% of placebo recipients. Surgical delay rates were also similar (4.5% with nivolumab and 3.9% with placebo). These effects represent potential complications requiring careful management throughout treatment.

Dosage

The FDA recommends nivolumab at 360 mg every three weeks for neoadjuvant treatment and 480 mg every four weeks for adjuvant treatment. When given on the same day as chemotherapy, nivolumab should be administered first.

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FDA Approvals for Operable Lung Cancer

With this nivolumab approval, there are now 6 FDA treatment approvals for operable NSCLC. They include atezolizumab and pembrolizumab as adjuvant therapy, nivolumab as neoadjuvant therapy, and pembrolizumab, durvalumab, and nivolumab as perioperative (both neoadjuvant and adjuvant) therapy.