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.
POSEIDON
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
- 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
- Durvalumab plus platinum-based chemotherapy for four cycles followed by durvalumab and maintenance chemotherapy
- Platinum-based chemotherapy for six cycles followed by maintenance chemotherapy.
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.
