Dr Skoulidis on the Implications of the POSEIDON Trial of Tremelimumab Plus Durvalumab in NSCLC

Ferdinandos Skoulidis, MD, PhD, MRCP, associate professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the clinical implications for data from the combination of tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and chemotherapy in metastatic non–small cell lung cancer (NSCLC) without sensitizing EGFR mutation or ALK aberrations.

In November 2022, the FDA approved tremelimumab plus durvalumab and platinum-based chemotherapy for adult patients with metastatic NSCLC without sensitizing EGFR mutations or ALK aberrations. The approval was supported by results of the phase 3 POSEIDON trial (NCT03164616), which showed that the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival (OS) vs chemotherapy alone at 14 months (95% CI, 11.7-16.1) vs 11.7 months (95% CI, 10.5-13.1), respectively (HR, 0.77; 95% CI, 0.65-0.92; 2-sided P = .00304).

POSEIDON generated excitement because it enabled the direct comparison of chemoimmunotherapy regimen encompassing an anti–PD-L1 inhibitor (durvalumab), with or without an anti–CTLA-4 inhibitor (tremelimumab), vs chemotherapy alone, Skoulidis says. This study uniquely addressed the question of whether patients could benefit for the combination of 2 agents with a chemotherapy backbone, or if there were subsets of patients who could benefit different combinations, Skoulidis expands.

One of the most important conclusions drawn from the trial was that patients with co-alterations, such as KEAP1 and STK11, were associated with primary resistance to immune checkpoint inhibitor monotherapy, or chemoimmunotherapy that includes only an anti–PD-(L)1 agent, Skoulidis notes. However, these patients did derive benefit from the addition of tremelimumab to durvalumab and chemotherapy in the POSEIDON study, Skoulidis emphasizes. Although these data stemmed from a subgroup analysis, the signal observed was strong and supports that the incorporation of tremelimumab plus durvalumab with chemotherapy for this subset of patients.

Additionally, these outcomes were in line with other studies in NSCLC that have also suggested some genomic subsets of patients may benefit from the incorporation of an anti–CTLA-4 agent to a chemoimmunotherapy backbone, Skoulidis notes. He says he currently uses tremelimumab plus durvalumab and chemotherapy in clinical practice specifically for patients with difficult-to-treat disease and baseline KEAP1 and STK11 co-alterations.