(Lung Cancer) Is Opdivo + Yervoy Effective?

On November 21, 2019, Matthew D. Hellmann published in The New England Journal of Medicine the "Efficacy and Safety Results of Combined Anti-PD-1 Antibody Opdivo (nivolumab) Plus Anti-CTLA-4 Antibody Yervoy (ipilimumab) as First-Line Treatment in Non-Small Cell Lung Cancer Patients in the CheckMate 227 Phase III Clinical Trial."

The CheckMate 227 Phase III clinical trial divided non-small cell lung cancer patients into two parts (Part 1a and Part 1b). The primary endpoint was overall survival in patients with PD-L1 expression of 1% or more, and the secondary endpoint was objective response rate.

Part 1a: Patients with NSCLC and PD-L1 expression of 1% or more were randomized to three groups as first-line treatment:

• Opdivo combination group (every 2 weeks: Opdivo 3mg/kg + every 6 weeks: Yervoy 1mg/kg)
• Opdivo monotherapy group (every 2 weeks: Opdivo 240mg)
• Chemotherapy group (every 3 weeks, up to 4 cycles)

Part 1b: Patients with NSCLC and PD-L1 expression below 1% were randomized to three groups:

• Opdivo combination group (every 2 weeks: Opdivo 3mg/kg + every 6 weeks: Yervoy 1mg/kg)
• Opdivo + chemotherapy group (every 3 weeks: Opdivo 360mg + chemotherapy, up to 4 cycles)
• Chemotherapy group (every 3 weeks, up to 4 cycles)

Patient backgrounds for the Opdivo combination and chemotherapy groups:

• Median age: 64 years (both groups)
• Sex: Opdivo combination: male 67.4%, female 32.6% / Chemotherapy: male 66.0%, female 34.0%
• Performance status: Opdivo combination ECOG=0: 35.0%, ECOG=1: 64.7% / Chemotherapy ECOG=0: 32.8%, ECOG=1: 66.2%
• Histology: Opdivo combination: squamous 28.0%, non-squamous 71.9% / Chemotherapy: squamous 27.8%, non-squamous 72.2%
• PD-L1: Opdivo combination: <1%: 32.1%, ≥1%: 67.9% / Chemotherapy: <1%: 31.9%, ≥1%: 68.1%
• TMB: Opdivo combination: ≥10mut/Mb: 42.1%, <10mut/Mb: 57.9% / Chemotherapy: ≥10mut/Mb: 45.8%, <10mut/Mb: 54.2%

Results for PD-L1 ≥1% (Part 1a): The median overall survival (primary endpoint) was 17.1 months for the Opdivo combination group versus 14.9 months for chemotherapy, showing improvement. The 1-year and 2-year overall survival rates were 62.6% and 40.0% for the Opdivo combination group versus 56.2% and 32.8% for chemotherapy. The objective response rate (secondary endpoint) was 35.9% versus 30.0%.

Results for PD-L1 <1% (Part 1b): The median overall survival was 17.2 months for the Opdivo combination group versus 12.2 months for chemotherapy, showing improvement. The 2-year overall survival rates were 40.4% for the Opdivo combination group versus 23.0% for chemotherapy.

Safety: The adverse event rate for all patients (Part 1a and 1b) was 76.7% for the Opdivo combination group versus 81.9% for chemotherapy. The most commonly observed adverse events were: Opdivo combination (diarrhea 17.0%, skin disorders 17.0%, fatigue 14.4%, decreased appetite 13.2%) versus chemotherapy (nausea 36.1%, anemia 33.0%, decreased appetite 19.6%, fatigue 18.9%, neutropenia 17.2%).

The rate of serious adverse events was 24.5% for the Opdivo combination group versus 13.9% for chemotherapy. Treatment discontinuation due to adverse events was 18.1% versus 9.1%, and treatment-related deaths were 1.4% versus 1.1%.

Based on the CheckMate 227 trial results, Matthew D. Hellmann concluded: "First-line treatment with anti-PD-1 antibody Opdivo plus anti-CTLA-4 antibody Yervoy improved overall survival compared to chemotherapy in non-small cell lung cancer patients, regardless of PD-L1 expression level."

Source: Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer (N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231.)

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Related Cancer Information

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