The Food and Drug Administration (FDA) approved the combination of nivolumab plus ipilimumab as first-line treatment for patients with metastatic non-small cell lung cancer whose tumour express PD-L1(≥1%), as determined by an FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations.

The FDA also approved the PD-L1 IHC 28-8 pharmDx (Agilent Technologies, Inc.) as a companion diagnostic device for selecting patients with NSCLC for treatment with nivolumab plus ipilimumab.

Efficacy was investigated in CHECKMATE-227 (NCT02477826), a randomised, open-label, multi-part trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

In Part 1a of the trial, 793 patients with PD-L1 tumour expression ≥1% were randomised to receive either the combination of nivolumab plus with ipilimumab (n=396) or platinum-doublet chemotherapy (n=397).

The trial demonstrated a statistically significant improvement in overall survival (OS) for patients with PD-L1 tumour expression ≥1% receiving nivolumab plus ipilimumab compared to those treated with  platinum-doublet chemotherapy.

Median OS was 17.1 months (95% CI: 15, 20.1) versus 14.9 (95% CI: 12.7, 16.7) (HR 0.79; 95% CI: 0.67, 0.94; p=0.0066).

Median progression-free survival (PFS) per blinded independent central review (BICR) was 5.1 months (95% CI: 4.1, 6.3) in the nivolumab plus ipilimumab arm and 5.6 months (95% CI: 4.6, 5.8) in the platinum-doublet chemotherapy arm (HR 0.82; 95% CI: 0.69, 0.97).

Confirmed overall response rate (ORR) per BICR was 36% (95% CI: 31, 41) and 30% (95% CI: 26, 35), respectively.

Median response duration was 23.2 months in the nivolumab plus  ipilimumab arm and 6.2 months in the platinum-doublet chemotherapy arm.

The most common adverse reactions in ≥20% of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhoea/colitis, dyspnea, cough, pruritis, nausea, and hepatitis.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.

Source: The Food and Drug Administration (FDA)

Watch our interview with Prof Sanjay Popat about the CheckMate-227 study here.