On November 10, the U.S. Food and Drug Administration (FDA) approved tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) and platinum-based chemotherapy for adult patients with metastatic non–small cell lung cancer (NSCLC) with no EGFR mutations or ALK genomic tumor aberrations.
Efficacy was evaluated in POSEIDON (ClinicalTrials.gov identifier: NCT03164616), 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
Treatment was continued until disease progression or unacceptable toxicity. This approval is based on a comparison of treatment arm 1 and 3 (675 patients).
The major efficacy outcome measures were progression-free survival assessed using blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1. and overall survival.
Tremelimumab plus durvalumab and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival compared to platinum-based chemotherapy (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.65–0.92, 2-sided P = .00304); median overall survival was 14 months (95% CI = 11.7–16.1) and 11.7 months (95% CI = 10.5–13.1) in treatment arms 1 and 3, respectively. Median progression-free survival was 6.2 months (95% CI = 5.0–6.5) and 4.8 months (95% CI = 4.6–5.8) in the treatment arms, respectively (HR = 0.72, 95% CI = 0.60–0.86, 2-sided P = .00031).
Overall response rate was 39% (95% CI = 34%–44%) and 24% (95% CI = 20%–29%) ins 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) in the same two treatment arms.
The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Reported 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 or more is 75 mg intravenously every 3 weeks with durvalumab at 1,500 mg and platinum-based chemotherapy for four cycles, then durvalumab at 1,500 mg with maintenance chemotherapy every 4 weeks. A fifth tremelimumab dose (of 75 mg) should be given at week 16. Using the above schedule, for patients weighing 30 kg or less, the recommended tremelimumab dose is 1 mg/kg and the durvalumab dose is 20 mg/kg.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.