Preoperative Immunotherapy for Early-Stage Lung Cancer Receives FDA Approval

For patients with early-stage, operable non-small cell lung cancer, as preoperative neoadjuvant (tumor-shrinking) therapy, nivolumab (Opdivo) received FDA (United States Food and Drug Administration) approval on 4 March 2022.

The Biggest Advance in Early-Stage Lung Cancer Treatment

This approval is revolutionary for lung cancer treatment and is the first FDA approval for neoadjuvant treatment of early-stage non-small cell lung cancer. It is also the first immunotherapy approval for early-stage lung cancer. Following this, preoperative tumor-shrinking immunochemotherapy became standard treatment for operable non-small cell lung tumors measuring 4 cm or larger that have not metastasized.

The CHECKMATE-816 Trial

The efficacy of Opdivo in these patients was evaluated in patients with surgically resectable Stage IB (≥4 cm), II or IIIA non-small cell lung cancer in CHECKMATE-816, a randomized, open-label clinical trial.

This trial included patients with no known activating genetic alterations in the EGFR or ALK genes.

Patients were enrolled regardless of tumor PD-L1 status. A total of 358 patients were randomly assigned to one of two groups to receive nivolumab plus platinum-based doublet chemotherapy administered every 3 weeks for up to 3 weeks, or platinum-based chemotherapy alone on the same schedule.

The main efficacy outcome measures were event-free survival and pathological complete response (pCR), assessed by blinded independent central review.

Results

Median event-free survival was 31.6 months in the nivolumab plus chemotherapy arm (95% Confidence Interval [CI] lower bound 30.2, upper bound not reached) and 20.8 months for those receiving chemotherapy alone (95% CI: 14.0, 26.7). Adding nivolumab to chemotherapy reduced the risk of an event such as cancer recurrence by 37%. The hazard ratio was 0.63 (HT 0.63 CI: 0.43, 0.91; p=0.0052).

The pathological complete response rate was 24% in the nivolumab plus chemotherapy arm (95% CI: 18.0, 31.0), compared with 2.2% (95% CI: 0.6, 5.6) in the chemotherapy-alone arm.

The most common side effects in patients (frequency ≥20%) were nausea, constipation, fatigue, decreased appetite and rash. Adding nivolumab to chemotherapy did not lead to more frequent delays or cancellations of surgery. Length of hospital stay after surgery and rates of adverse reactions identified as surgical complications were similar for patients in both trial arms.

The recommended nivolumab dose is 360 mg every 3 weeks for 3 cycles, on the same day as platinum-doublet chemotherapy.