FDA approved Tremelimumab plus Durvalumab & chemo for metastatic NSCLC
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The Food and Drug Administration (FDA) approved AstraZeneca’s tremelimumab in combination with durvalumab and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
This approval was granted based on POSEIDON Trial (NCT03164616), a randomized (1:1:1), multicenter, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. In the study, patients were randomized to one of three treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for 4 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 4 cycles followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy. This approval was based on a comparison of treatment arms 1 and 3 (675 patients), and treatment was continued until disease progression or unacceptable toxicity.
The primary efficacy outcome measures were progression-free survival assessed using a blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1. and overall survival. Analysis showed 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).
The overall response rate was 39% (95% CI = 34%–44%) and 24% (95% CI = 20%–29%) ins treatment arms 1 and 3, respectively. At the same time, the 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.
