CheckMate 227 is a large phase 3 study of first-line Nivolumab plus Ipilimumab, Nivolumab, or Nivolumab plus chemotherapy vs chemotherapy in advanced non-small cell lung cancer ( NSCLC ).
The study met its co-primary endpoint demonstrating significantly prolonged progression-free survival with Nivolumab plus Ipilimumab versus chemotherapy in patients with tumor mutational burden greater than or equal to 10 mutations/Mb.
The safety profile of first-line Nivolumab plus low-dose Ipilimumab was consistent with previous reports.
Patients ( n=1739 ) with chemotherapy-naive, stage IV / recurrent NSCLC without known sensitizing EGFR / ALK mutations were randomized 1:1:1 to Nivolumab ( 3 mg/kg Q2W) plus Ipilimumab ( 1 mg/kg Q6W ), Nivolumab monotherapy ( 240 mg Q2W ), or chemotherapy for patients with greater than or equal to 1% tumor PD-L1 expression and to Nivolumab plus Ipilimumab, Nivolumab ( 360 mg Q3W ) plus chemotherapy, or chemotherapy for patients with less than 1% tumor PD-L1 expression.
Treatment continued until disease progression or unacceptable toxicity for up to 2 years.
Safety and patient-reported outcomes were exploratory endpoints. Safety analyses included time to onset and resolution of select treatment-related adverse events ( select TRAEs; those with a potential immunologic cause ) and corticosteroid use. Patient-reported outcomes were assessed using the Lung Cancer Symptom Scale and EQ-5D instruments.
Minimum follow-up was 11.2 months. Median duration of therapy was 4.2 months with Nivolumab plus Ipilimumab and 2.6 months with chemotherapy.
Rates of any grade and grade 3–4 treatment-related adverse events were 75% and 31% with Nivolumab plus Ipilimumab, and 81% and 36% with chemotherapy, respectively.
Treatment-related adverse events led to discontinuation in 17% of patients receiving Nivolumab plus Ipilimumab and in 9% of patients receiving chemotherapy.
Most frequent grade 3–4 select treatment-related adverse events in patients receiving Nivolumab plus Ipilimumab were hepatic ( 8% ), endocrine ( 4% ), skin ( 4% ), pulmonary ( 3% ), and gastrointestinal ( 2% ).
Median time to onset of select treatment-related adverse events ranged from 2–15 weeks, and the majority resolved with corticosteroid use ( median time to resolution was less than or equal to 10 weeks ).
In CheckMate 227, Nivolumab plus low-dose Ipilimumab was well tolerated in non-small cell lung cancer.
Toxicities were manageable with previously established treatment algorithms, including corticosteroids. ( Xagena )
Source: American Society of Clinical Oncology - ASCO Meeting, 2018