In the recently completed CheckMate 817 trial, researchers evaluated flat-dose nivolumab plus weight-adjusted ipilimumab as a first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). According to the study’s authors, the nivolumab plus ipilimumab regimen was associated with durable response and manageable safety in the primary cohort of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1. The findings were reported in the Journal for the Immunotherapy of Cancer.
In addition, the team reported that nivolumab with ipilimumab showed manageable treatment-related toxicity and a clinically meaningful 3-year overall survival (OS) rate in higher-risk subgroups including patients with ECOG PS 2, ECOG PS 0-1 with untreated brain metastases, renal impairment, hepatic impairment, or controlled HIV infection. Investigators noted these findings were comparable to results from previous phase 3 studies on patients with metastatic NSCLC.
Nivolumab Plus Ipilimumab Shows Promise for NSCLC
The clinical trial enrolled 391 patients with NSCLC in the primary cohort and 198 patients in the special populations cohort. Both groups received nivolumab 240 mg every 2 weeks plus ipilimumab 1 mg per kg every 6 weeks.
The primary end points were grade III-IV and grade V immune-mediated adverse events (AEs) within 100 days of last study dose treated with immunomodulating medication, and treatment-related AEs with potential immunological etiology requiring frequent intervention from first dose through to 30-days after last dose.
According to the report, the most common grade III-IV immune-mediated AEs in the primary cohort were pneumonitis (5.1%), diarrhea or colitis (4.9%), and hepatitis (4.6%). In the special populations cohort, the most common events were diarrhea or colitis (3.5%), hepatitis (3.5%), and rash (3.0%).
The most common grade III-IV treatment-related AEs in the primary group were:
- Hepatic (5.9%)
- Gastrointestinal (4.9%)
- Pulmonary (4.6%)
Comparatively, the most common events in the special populations group were:
- Gastrointestinal (4.0%)
- Skin (3.5%)
- Endocrine (3.0%)
Authors added that no grade V immune-mediated or treatment-related AEs were reported with first-line fixed-dose nivolumab plus weight-adjusted ipilimumab. Deaths related to treatment occurred in 4 (1.0%) and 3 (1.5%) patients and rate of 3-year OS was 33.7% and 20.5% in the primary and special cohorts, respectively.
Though CheckMate 817 was a prospective investigation, the study’s authors noted findings were limited by the single-arm design. Further, specific benefit to patients with NSCLC with brain metastases was not evaluable due to limited data collection and the renal impairment, hepatic impairment, and HIV-positive subgroups had small samples which limited analyses to descriptive characteristics only.
“In conclusion,” the authors summarized, “flat-dose nivolumab plus weight-based ipilimumab among patients with ECOG PS 0–1 was associated with manageable safety and durable efficacy, consistent with outcomes with weight-based nivolumab plus weight-based ipilimumab in metastatic NSCLC.”
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