Melissa L. Johnson, MD
As reported in the Journal of Clinical Oncology by Melissa L. Johnson, MD, and colleagues, the pivotal phase III POSEIDON trial has shown significantly improved progression-free and overall survival with the addition of tremelimumab and durvalumab to platinum-based chemotherapy in the first-line treatment of metastatic non–small cell lung cancer (NSCLC) without EGFR/ALK alterations.
The trial supported the November 10, 2022, approval of tremelimumab in combination with durvalumab plus chemotherapy in this setting.
In the open-label trial, 1,013 patients from sites in 18 countries were randomly assigned 1:1;1 between June 2017 and September 2018 to receive either:
Chemotherapy options included carboplatin plus nab-paclitaxel regardless of histology; cisplatin or carboplatin plus gemcitabine for squamous histology; and cisplatin or carboplatin plus pemetrexed (with pemetrexed maintenance if eligible) for nonsquamous histology.
The primary endpoints were progression-free and overall survival for durvalumab plus chemotherapy vs chemotherapy; key secondary endpoints were progression-free and overall survival for tremelimumab/durvalumab plus chemotherapy.
Progression-Free and Overall Survival
At data cutoffs in July 2019 for progression-free survival and in March 2021 for overall survival, median follow-up durations for censored patients were 10.3 months (range = 0.0–23.1 months) and 34.9 months (range = 0.0–44.5 months), respectively.
For the durvalumab plus chemotherapy group vs chemotherapy group, median progression-free survival was 5.5 vs 4.8 months (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.62–0.89, P = .0009) and median overall survival was 13.3 vs 11.7 months (HR = 0.86, 95% CI = 0.72–1.02, P = .0758); overall survival at 24 months was 29.6% vs 22.1%.
For the tremelimumab/durvalumab plus chemotherapy group vs chemotherapy group, median progression-free survival was 6.2 vs 4.8 months (HR = 0.72, 95% CI = 0.60–0.86, P = .0003) and median overall survival was 14.0 vs 11.7 months (HR = 0.77, 95% CI = 0.65–0.92, P = .0030); overall survival at 24 months was 32.9% vs 22.1%.
Totals of 36.4% of patients in the tremelimumab/durvalumab plus chemotherapy group, 41.1% of the durvalumab plus chemotherapy group, and 57.6% of the chemotherapy group received subsequent systemic anticancer therapy. Second-line immunotherapy was received by 33.2% of patients in the chemotherapy group and by 6.5% of the other two groups, whereas rates of second-line chemotherapy were similar across groups.
Treatment-related grade 3 or 4 adverse events occurred in 51.8% of patients in the tremelimumab/durvalumab plus chemotherapy group, 44.6% of the durvalumab plus chemotherapy group, and 44.4% of the chemotherapy group; the most common in all groups were anemia (17.3%, 15.3%, 20.4%, respectively) and neutropenia (16.1%, 12.6%, 12.0%, respectively). Serious treatment-related adverse events occurred in 27.6%, 19.5%, and 17.7% of patients, respectively. Treatment-related adverse events led to discontinuation of therapy in 15.5%, 14.1%, and 9.9%, respectively. Death related to treatment occurred in 11 patients (3.3%), 7 patients (2.1%), and 8 patients (2.4%), respectively.
The investigators concluded, “Durvalumab plus chemotherapy significantly improved progression-free survival vs chemotherapy. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved overall survival and progression-free survival vs chemotherapy, without meaningful additional tolerability burden, representing a potential new option in first-line metastatic NSCLC.”
Dr. Johnson, of Sarah Cannon Research Institute—Tennessee Oncology, Nashville, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.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®.