The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur
On March 4, 2022, the Food and Drug Administration approved nivolumab (Opdivo, Bristol-Myers Squibb Company) with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting.
This represents the first FDA approval for neoadjuvant therapy for early-stage NSCLC.
Efficacy was evaluated in CHECKMATE-816 (NCT02998528), a randomized, open-label trial in patients with resectable, histologically confirmed Stage IB (≥4 cm), II, or IIIA NSCLC (AJCC/UICC staging criteria) and measurable disease (RECIST v1.1.). Patients were enrolled regardless of the tumor PD-L1 status. A total of 358 patients were randomized to receive either nivolumab plus platinum-doublet chemotherapy administered every 3 weeks for up to 3 cycles, or platinum-chemotherapy alone administered on the same schedule.
The main efficacy outcome measures were event-free survival (EFS) and pathologic complete response (pCR) by blinded independent central review. Median EFS was 31.6 months (95% CI: 30.2, not reached) in the nivolumab plus chemotherapy arm and 20.8 months (95% CI: 14.0, 26.7) for those receiving chemotherapy alone. The hazard ratio was 0.63 (97.38% CI: 0.43, 0.91; p=0.0052). The pCR rate was 24% (95% CI: 18.0, 31.0) in the nivolumab plus chemotherapy arm and 2.2% (95% CI: 0.6, 5.6) in the chemotherapy alone arm.
The most common adverse reactions (incidence ≥20%) occurring in patients were nausea, constipation, fatigue, decreased appetite, and rash. The addition of nivolumab to chemotherapy did not result in more frequent delays or cancellations of surgery. The median lengths of hospital stays following definitive surgery and the rates of adverse reactions identified as surgical complications were similar for patients in both arms of the trial.
The recommended nivolumab dose is 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for 3 cycles.
View full prescribing information for Opdivo.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews may be ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application five months ahead of the FDA goal date.
This application was granted priority review, breakthrough designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
For information on the COVID-19 pandemic, see the following resources:
- FDA: Coronavirus Disease 2019 (COVID-19)
- NCI: Coronavirus: What People With Cancer Should Know
- CDC: Coronavirus (COVID-19)
Follow the Oncology Center of Excellence on Twitter @FDAOncology.
Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.
