Posted: Thursday, November 17, 2022
On November 10, the U.S. Food and Drug Administration (FDA) approved the CTLA-4 inhibitor tremelimumab (Imjudo) in combination with the PD-L1 inhibitor durvalumab (Imfinzi) and platinum-based chemotherapy for adults with metastatic non–small cell lung cancer (NSCLC) with no sensitizing EGFR mutation or ALK genomic tumor aberrations.
Efficacy was evaluated in the phase III POSEIDON trial, a randomized (1:1:1), multicenter, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. Patients were randomly assigned to one of three treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for four cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks. Patients were treated with a fifth tremelimumab dose at week 16; (2) durvalumab plus platinum-based chemotherapy for four cycles followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for six cycles followed by maintenance chemotherapy. This approval is based on a comparison of treatment arms 1 and 3 (675 patients).
Tremelimumab plus durvalumab and platinum-based chemotherapy (arm 1) demonstrated a statistically significant and clinically meaningful improvement in overall survival compared with platinum-based chemotherapy (hazard ratio [HR] = 0.77 [95% confidence interval [CI] = 0.65–0.92], two-sided P = .00304); median overall survival was 14 months (95% CI = 11.7–16.1 months) and 11.7 months (95% CI = 10.5–13.1 months) in treatment arms 1 and 3, respectively. Median progression-free survival was 6.2 months (95% CI = 5.0–6.5 months) and 4.8 months (95% CI = 4.6–5.8 months) in treatment arms 1 and 3, respectively (HR = 0.72 [95% CI = 0.60–0.86], two-sided P = .00031).
Overall response rate was 39% (95% CI = 34%–44%) and 24% (95% CI = 20%–29%) in treatment arms 1 and 3, respectively. Median duration of response was 9.5 months (95% CI = 7.2 to not reached) and 5.1 months (95% CI = 4.4–6.0 months) in the two treatment arms.
The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia.
The recommended tremelimumab dose for patients weighing ≥ 30 kg is 75 mg intravenously (IV) every 3 weeks, with durvalumab at 1,500 mg IV and platinum-based chemotherapy for four cycles, then durvalumab at 1,500 mg with maintenance chemotherapy every 4 weeks. A fifth tremelimumab dose (75 mg) should be given at week 16. Using the previous schedule, for patients weighing ≤ 30 kg, the recommended tremelimumab dose is 1 mg/kg, and the durvalumab dose is 20 mg/kg.