CheckMate 227, a phase 3 study of first-line Nivolumab ( Opdivo ) plus Ipilimumab ( Yervoy ), Nivolumab, or Nivolumab plus chemotherapy vs chemotherapy in advanced non-small cell lung cancer ( NSCLC ), met its co-primary endpoint of prolonged progression-free survival ( PFS ) with Nivolumab plus Ipilimumab vs chemotherapy in patients with tumor mutational burden greater than or equal to 10 mutations/Mb.
Identifying effective treatment for patients without known predictive biomarkers remains an unmet need.
Prior studies suggest addition of chemotherapy to anti–PD-(L)1 treatment can improve outcomes in an unselected patient population, although benefit is most pronounced in patients with higher tumor PD-L1 expression.
Researchers have reported results for Nivolumab plus chemotherapy versus chemotherapy in patients with less than 1% tumor PD-L1 expression.
Patients ( n = 550 ) with chemotherapy-naive, stage IV/recurrent NSCLC, no known sensitizing EGFR/ALK mutations, and less than 1% tumor PD-L1 expression were stratified by tumor histology and randomized 1:1:1 to Nivolumab 3 mg/kg Q2W plus Ipilimumab 1 mg/kg Q6W, Nivolumab 360 mg Q3W plus chemotherapy, or chemotherapy ( optional Pemetrexed maintenance after chemotherapy for nonsquamous [ non-SQ ] NSCLC ).
Patients were treated up to 2 years.
A descriptive analysis was performed for the secondary endpoint of PFS for Nivolumab plus chemotherapy versus chemotherapy in patients with less than 1% tumor PD-L1 expression.
Baseline characteristics were balanced between Nivolumab plus chemotherapy ( n=177 ) and chemotherapy ( n=186 ) arms.
Progression-free survival was improved with Nivolumab plus chemotherapy vs chemotherapy ( hazard ratio, HR=0.74 [ 95% CI: 0.58, 0.94 ]; minimum follow-up 11.2 months; descriptive comparison ).
PFS benefit with Nivolumab plus chemotherapy was observed across most subgroups. Among histologic subgroups, benefit was more pronounced in non-SQ ( HR = 0.68 ) relative to SQ NSCLC ( HR = 0.92 ).
Rates of any grade treatment-related adverse events leading to discontinuation were 13% with Nivolumab plus chemotherapy and 14% with chemotherapy.
In conclusion, first-line Nivolumab plus chemotherapy has improved progression-free survival versus chemotherapy in patients with advanced NSCLC and less than 1% tumor PD-L1 expression, and was well tolerated.
Results are encouraging in this analysis, which includes only patients with less than 1% PD-L1.
CheckMate 227 Part 2 ( ongoing ) is evaluating Nivolumab plus chemotherapy vs chemotherapy irrespective of PD-L1 expression. ( Xagena )
Source: American Society of Clinical Oncology - ASCO Meeting, 2018