FDA approves immuno-oncology combination as first-line treatment in patients with NSCLC who express positive PD-L1 greater than 1%
Results of the CheckMate 227 trial demonstrate gains in overall survival with the dual immunotherapy approach with nivolumab and ipilimumab
The US Food and Drug Administration has approved the combination of nivolumab and ipilimumab as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing positive PD-L1 (≥1%), but absence of changes in EGFR or ALK.
The effectiveness of combining anti-PD-1 (nivolumab) with anti-CTLA-4 (ipilimumab) was investigated in the CHECKMATE-227 trial (NCT02477826), a phase 3, randomized, open study that examined the safety and efficacy of treatment in NSCLC patients not exposed to previous antineoplastic therapy.
In the first part of the trial, the primary outcome was overall survival (OS). 793 patients with PD-L1 expression ≥1% were randomized to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). The results showed a statistically significant improvement of the first versus the second: 17.1 months (95% CI: 15, 20.1) versus 14.9 (95% CI: 12.7, 16.7) (HR 0.79; 95% CI: 0.67, 0.94; p = 0.0066), respectively.
The median progression-free survival (PFS) analyzed by blinded independent central review (BICR) was 5.1 months (95% CI: 4.1, 6.3) in the nivolumab plus ipilimumab arm and 5.6 months (CI 95%: 4.6; 5.8) in the platinum-doublet chemotherapy arm (HR 0.82; 95% CI: 0.69, 0.97). The overall response rate (ORR) confirmed by BICR was 36% (95% CI: 31, 41) and 30% (95% CI: 26, 35), respectively. The median response duration was 23.2 months in the nivolumab plus ipilimumab arm and 6.2 months in the platinum-doublet chemotherapy arm.
Treatment-related adverse events (TRAEs) were reported in 76.7% of patients receiving nivolumab / ipilimumab and grade 3/4 TRAES were seen in 32.8%. The most common TRAES with immunotherapy regimen were fatigue, rash, loss of appetite, musculoskeletal pain, diarrhea / colitis, dyspnea, cough, pruritus, nausea, and hepatitis.
The recommended doses for the treatment of NSCLC are nivolumab 3 mg / kg every 2 weeks and ipilimumab 1 mg / kg every 6 weeks until disease progression, unacceptable toxicity or up to 2 years in patients without disease progression.
At the same time, the FDA approved the PD-L1 IHC 28-8 pharmDx test (Agilent Technologies, Inc.) as a complementary diagnostic device to select patients with NSCLC who can benefit from this treatment.
References:
Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H. Nivolumab plus ipilimumab in advanced non–small-cell lung cancer. New England Journal of Medicine. 2019;381(21):2020-31.
FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%) BMS [news release]. FDA; May 15, 2020. https://bit.ly/3cwvlo2. Accessed May 15, 2020.
U.S. Food and Drug Administration Approves Opdivo® (nivolumab) + Yervoy® (ipilimumab) as First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer Whose Tumors Express PD-L1≥1% [news release]. Princeton, NJ: Bristol Myers Squibb; May 15, 2020. https://bit.ly/3bE54CW. Accessed May 15, 2020.
