FDA approves combination therapy of tremelimumab, durvalumab, and platinum-based chemotherapy for metastatic NSCLC
The U.S. Food and Drug Administration (FDA) have approved tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations1.
Tremelimumab and durvalumab are immune checkpoint inhibitors with complimentary mechanisms of action that enhance T-cell action against tumour cells. Tremelimumab is a monoclonal antibody that inhibits cytotoxic T-lymphocyte antigen 4 (CTLA-4), while durvalumab is a monoclonal antibody that blocks PD-L1 binding to PD-1, inhibiting the PD-L1/PD-1 pathway2.
Immune checkpoint inhibitors acting against the PD-L1/PD-1 pathway, such as durvalumab, were previously the only immunotherapies available for locally advanced, unresectable NSCLC after chemoradiotherapy, with durvalumab having received FDA approval in February 2018 based on the results of the Phase III PACIFIC trial3. However, patients with low or negative PD-1 expression are less likely to benefit from durvalumab as a monotherapy. Tremelimumab in combination with durvalumab was approved by the FDA for the treatment of hepatocellular carcinoma in October 20224.
The randomized, multicenter, open-label, Phase III POSEIDON trial (NCT03164616) investigated the efficacy of tremelimumab in combination with durvalumab with platinum-based chemotherapy in metastatic NSCLC patients with no EGFR or ALK genomic tumour aberrations who had not received previous systemic therapy. Patients were randomized to one of three arms, until disease progression or unacceptable toxicity: tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab every 4 weeks, with an additional dose of tremelimumab at week 16; durvalumab and platinum-based chemotherapy for 4 cycles, followed by durvalumab every 4 weeks; or platinum-based chemotherapy for 6 cycles1,2,5.
In an interview with VJOncology at the European Society for Medical Oncology (ESMO) 2022 Congress, Dr Melissa Johnson, MD, Sarah Cannon Research Institute, Nashville, TN, discusses the study design and presents the four-year follow-up data of the POSEIDON trial.
The trial reported a statistically significant improvement in both overall survival (OS) and progression-free survival (PFS) in the treatment arm receiving tremelimumab, durvalumab and platinum-based chemotherapy compared with platinum-based chemotherapy alone2. Median PFS was 6.2 months (95% CI: 5.0, 6.5) compared with 4.8 months (95% CI 4.6, 5.8) respectively (hazard ratio [HR] of 0.72; 95% CI: 0.60, 0.86; p-value = 0.0003). Median OS was 14 months in the combination arm (95% CI: 11.7, 16.1) compared with 11.7 months in the monotherapy arm (95% CI: 10.5, 13.1) (HR of 0.77; 95% CI: 0.65, 0.92; p-value = 0.003). Immune-mediated adverse events (AEs) were well tolerated and generally low grade, and the combination therapy did not lead to increased discontinuation of treatment2.
The approval of tremelimumab in conjunction with durvalumab and platinum-based chemotherapy potentially fulfils an unmet need for metastatic NSCLC patients, particularly for PD-1-negative and PD-1-low subgroups who have suboptimal outcomes with current treatment options.
Written by Natalie Harris
Edited by Helena Gibbon
- FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. U.S. Food and Drug Administration. 2022 [cited 21 November 2022]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-and-platinum-based-chemotherapy-metastatic-non
- Johnson, ML, et al. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study. Journal of Clinical Oncology. 2022.
- FDA approves durvalumab after chemoradiation for unresectable stage III NSCLC. U.S. Food and Drug Administration. 2018 [cited 21 November 2022]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-after-chemoradiation-unresectable-stage-iii-nsclc
- FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. U.S. Food and Drug Administration. 2022 [cited 21 November 2022]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma
- Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). (POSEIDON). Clinical Trials.gov. National Library of Medicine (US). 2022 [cited 21 November 2022]. Available from: https://clinicaltrials.gov/ct2/show/NCT03164616