- In patients with previously untreated advanced Non-Small Cell Lung Cancer (NSCLC), the combination nivolumab+ipilimumab has a consistent safety profile in special populations, including patients with comorbidities or an Eastern Cooperative Oncology Group performance status (ECOG-PS) 2.
- Results on efficacy are encouraging.
- Efficacy seems to improve in patients with high tumour molecular burden (TMB) or higher tumour PD-L1 expression.
Why this matters
- Patients with ECOG-PS 2 or comorbidities represent a large proportion of NSCLC patients, frequently excluded from registration trials.
- Limited data is available on immunotherapy in these frail populations.
- All patients had untreated advanced NSCLC, without known sensitizing EGFR or ALK alterations.
- Cohort A (n=391) included patients with ECOG-PS 0-1; cohort A1 (special populations, n=198) included patients with ECOG-PS 2 or ECOG-PS 0-1 and one comorbidity (asymptomatic untreated brain metastases, hepatic or renal impairment, HIV).
- Cohort A1 patients were grouped as ECOG-PS 2 (n=139) and all other special populations (AOSP, n=59).
- Treatment consisted in flat-dose nivolumab (240 mg) plus weight-based ipilimumab (1 mg/kg) for two years or until disease progression/unacceptable toxicity.
- Cohort A1 analyses were exploratory; endpoints included treatment-related select adverse events (TRAEs), severe AEs, IMAEs, progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and overall survival (OS).
- Efficacy by TMB and PD-L1 was assessed in both cohorts.
- A consistent safety profile was observed between cohort A and A1, with rates of grade 3-4 TRAEs of 35% and 28%, respectively, and higher in AOSP versus the ECOG-PS 2 subgroup.
- In cohort A1, ORR was 24%, 19%, and 37%, in all treated patients, ECOG-PS 2 and AOSP, respectively.
- Corresponding 1-year rates for DOR were 57%, 65% and 45%; 1-year rates for PFS were 26%, 25% and 27%.
- In both cohort A and A1, a longer PFS was observed in patients with high TMB (≥10 mut/Mb) and higher PD-L1 expression (≥1% or ≥50%).
“If there is a place for ipilimumab-nivolumab in first-line treatment of NSCLC, then Checkmate 817 provides us with excellent evidence that it is safe and efficacious in the given patient population”. Martin Sebastian. University Hospital Frankfurt, Germany.