POSEIDON Trial: Dual Checkpoint Blockade Plus Chemotherapy Improves Survival in First-Line Metastatic NSCLC

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Findings from the phase III POSEIDON trial showed significantly improved progression-free and overall survival in patients with metastatic non–small cell lung cancer (NSCLC) who received first-line durvalumab and tremelimumab plus chemotherapy vs chemotherapy alone. These findings were presented by Melissa L. Johnson, MD, and colleagues at the International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer (Abstract PL02.01).

When combined with chemotherapy, durvalumab plus tremelimumab reduced the risk of death by 23%, with a median overall survival of 14.0 months vs 11.7 months for chemotherapy alone. Median progression-free survival also improved to 6.2 months with dual checkpoint inhibition plus chemotherapy compared with 4.8 months for chemotherapy alone.

“The POSEIDON trial showed that patients who received durvalumab and tremelimumab and chemotherapy experienced statistically significant and clinically meaningful improvements in both progression-free and overall survival compared with patients on chemotherapy alone,” said lead study author Dr. Johnson, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute. “Durvalumab plus tremelimumab plus chemotherapy represents a potential new front-line treatment option for metastatic NSCLC.”

Durvalumab plus tremelimumab plus chemotherapy represents a potential new front-line treatment option for metastatic NSCLC.
— Melissa L. Johnson, MD

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As Dr. Johnson reported, PD-1/PD-L1 checkpoint inhibitors have transformed the treatment of metastatic NSCLC as monotherapy as well as in combination with chemotherapy, with emerging evidence that adding anti–CTLA-4 therapy to anti–PD-1/PD-L1 therapy may further improve survival outcomes.

In the randomized, open-label POSEIDON trial, Dr. Johnson and colleagues enrolled 1,013 patients from 153 cancer centers around the world. The study evaluated the PD-1 inhibitor durvalumab with and without the CTLA-4 inhibitor tremelimumab in combination with chemotherapy regimens as first-line treatment for squamous or nonsquamous metastatic NSCLC.

Investigators had their choice of five different chemotherapy regimens: platinum and gemcitabine for patients with squamous histology; platinum and pemetrexed for patients with nonsquamous histology; and nab-paclitaxel and carboplatin for patients with either histology.

Results of the study showed improved progression-free survival with first-line durvalumab plus chemotherapy compared with chemotherapy alone (5.5 months vs 4.8 months) in patients with metastatic NSCLC, with a trend toward improved overall survival.

First-line durvalumab plus tremelimumab plus chemotherapy also demonstrated a statistically significant improvement in both progression-free survival and overall survival vs chemotherapy, especially among patients with nonsquamous histology. 

The overall safety profile was similar to previous reports of immunotherapy plus chemotherapy regimens, with no new safety signals identified with the addition of tremelimumab. Adding tremelimumab to durvalumab plus chemotherapy did not lead to a meaningful increase in treatment discontinuation, Dr. Johnson reported.

Disclosure: This study was sponsored by AstraZeneca.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.