In the phase 3 CheckMate 227 Part 1 ( minimum follow-up, 29.3 months ), first line 1L Nivolumab ( Opdivo ) + Ipilimumab ( Yervoy ) has significantly improved overall survival ( OS ) versus chemotherapy in treatment-naive patients with advanced non-small cell lung cancer ( aNSCLC ) and tumor PD-L1 expression greater than or equal to 1% ( primary analysis ) or less than 1% ( pre-specified descriptive analysis ).
Researchers have reported data with minimum follow-up of 3-years.
Patients with stage IV / recurrent NSCLC and PD-L1 greater than or equal to 1% ( n = 1189 ) were randomized 1:1:1 to Nivolumab ( 3 mg/kg Q2W [ once every 2 weeks ] ) + Ipilimumab ( 1 mg/kg Q6W [ once every 6 weeks ] ), Nivolumab ( 240 mg Q2W ) alone, or chemotherapy.
Patients with PD-L1 less than 1% ( n = 550 ) were randomized to Nivolumab + Ipilimumab, Nivolumab ( 360 mg Q3W ) + chemotherapy, or chemotherapy.
Primary endpoint was overall survival ( OS ) with Nivolumab + Ipilimumab vs chemotherapy in patients with PD-L1 greater than or equal to 1%.
An exploratory analysis of overall survival in patients by response status ( CR [ complete response ] / PR [ partial response ), stable disease [ SD ], progressive disease [ PD ] ) at 6 months was conducted.
After a median follow-up of 43.1 months ( database lock, 28 Feb 2020 ), patients with PD-L1 greater than or equal to 1% continued to derive overall survival benefit from Nivolumab + Ipilimumab vs chemotherapy ( hazard ratio, HR=0.79; 95% CI, 0.67–0.93 ); 3-year OS rates were 33% ( Nivolumab + Ipilimumab ), 29% ( Nivolumab ), and 22% ( chemotherapy ).
At 3 years, 18% of patients with PD-L1 greater than or equal to 1% treated with Nivolumab + Ipilimumab remained progression-free versus 12% with Nivolumab and 4% with chemotherapy; 38% of confirmed responders remained in response in the Nivolumab + Ipilimumab arm at 3 years vs 32% in the Nivolumab arm and 4% in the chemotherapy arm.
In patients with PD-L1 less than 1%, OS hazard ratio for Nivolumab + Ipilimumab vs chemotherapy was 0.64 ( 95% CI, 0.51–0.81 ); 3-year OS rates were 34% ( Nivolumab + Ipilimumab ), 20% ( Nivolumab + chemotherapy ), and 15% ( chemotherapy ); 13%, 8%, and 2% of patients remained progression-free; and 34%, 15%, and 0% of confirmed responders remained in response, respectively.
Patients with PD-L1 greater than or equal to 1% with either CR/PR at 6 months had longer subsequent overall survival with Nivolumab + Ipilimumab vs chemotherapy; patients with stable disease or progressive disease at 6 months had generally similar subsequent overall survival between treatments.
Any-grade / grade 3–4 treatment-related adverse effects were observed in 77% / 33% of all patients treated with Nivolumab + Ipilimumab, and 82% / 36% with chemotherapy.
In conclusion, with 3 year minimum follow-up, Nivolumab + Ipilimumab continued to provide durable and long-term OS benefits versus chemotherapy for patients in 1L aNSCLC.
Patients with PD-L1 greater than or equal to 1% who achieved CR/PR at 6 months had marked OS benefit with Nivolumab + Ipilimumab vs chemotherapy.
No new safety signals were identified for Nivolumab + Ipilimumab. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020