FDA Approves Tremelimumab Plus Durvalumab and Platinum-Based Chemotherapy for Metastatic NSCLC

On November 10, 2022, The US Food and Drug Administration (FDA) granted approval to tremelimumab, in combination with durvalumab and platinum-based chemotherapy, to treat adult patients with metastatic non-small cell lung cancer (NSCLC) and no sensitizing epidermal growth factor receptor (EFGR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

This approval was based on results from the randomized, multicenter, active-controlled, open-label POSEIDON trial. Patients were randomized into one of 3 treatment arms (1:1:1). Patients in arm 1 received tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks, with a fifth dose of tremelimumab at week 16. Arm 2 patients were treated with durvalumab plus platinum-based chemotherapy for 4 cycles followed by durvalumab and maintenance chemotherapy, and patients in treatment arm 3 received platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy.

Approval was granted based on comparison of data from treatment arm 1 and 3 (n = 675). Primary efficacy measures were progression-free survival (PFS) and overall survival (OS).

Patients in treatment arm 1 experienced significant, meaningful improvement in OS compared to patients in arm 3 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.92; 2-sided P-value = .003), with median OS of 14 months (95% CI, 11.7 to 16.1) in treatment arm 1 and 11.7 months (95% CI, 10.5 to 13.1) in treatment arm 3. Median PFS was also improved in patients treated with tremelimumab plus durvalumab and platinum-based chemotherapy vs platinum-based chemotherapy alone (6.2 months [95% CI, 5.0 to 6.5] vs 4.8 months [95% CI, 4.6 to 5.8]; HR, 0.72 [95% CI, 0.60 to 0.86], 2-sided P-value = .0003).

The most common adverse reactions occurring in ≥20% of patients were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea, with grade 3 or 4 reactions of neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia occurring in ≥10% of patients.

Source:

FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. United States Food and Drug Administration. November 10, 2022. Accessed November 11, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-and-platinum-based-chemotherapy-metastatic-non