March 2022: In the neoadjuvant setting, the FDA approved nivolumab (Opdivo, Bristol-Myers Squibb Company) in combination with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC).
This is the first time the FDA has approved neoadjuvant therapy for early-stage NSCLC.
Efficacy was assessed in CHECKMATE-816 (NCT02998528), a randomised, open-label trial in patients with detectable disease and resectable, histologically proven Stage IB (4 cm), II, or IIIA NSCLC (AJCC/UICC staging criteria) (RECIST v1.1.). Patients were included regardless of PD-L1 status in the tumour. A total of 358 patients were randomly assigned to undergo nivolumab plus platinum-doublet chemotherapy every three weeks for up to three cycles, or platinum-chemotherapy alone on the same schedule.
By blinded independent central review, the key efficacy outcome measures were event-free survival (EFS) and pathologic complete response (pCR). The median EFS for those getting nivolumab + chemotherapy was 31.6 months (95 percent confidence interval: 30.2, not reached) compared to 20.8 months (95 percent confidence interval: 14.0, 26.7) for those receiving chemotherapy alone. The hazard ratio was 0.63 (p=0.0052; 97.38 percent CI: 0.43, 0.91). The pCR rate in the nivolumab plus chemotherapy arm was 24 percent (95 percent CI: 18.0, 31.0) and 2.2 percent (95 percent CI: 0.6, 5.6) in the chemotherapy alone arm.
Nausea, constipation, exhaustion, decreased appetite, and rash were the most prevalent adverse events in patients (incidence 20%). The addition of nivolumab to chemotherapy did not result in an increase in the number of surgery delays or cancellations. Patients in both arms of the experiment had similar median lengths of hospital stays following definitive surgery and rates of adverse responses recognised as surgical complications.
The suggested nivolumab dose is 360 mg every three weeks with platinum-doublet chemotherapy on the same day.
