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Late-Breaking Developments From the POSEIDON Trial

Late-Breaking Developments From the POSEIDON Trial

Video: Dr Melissa Johnson Discusses the POSEIDON Trial


Late-Breaking Developments From the POSEIDON Trial


Results of late-breaking developments from the POSEIDON Phase III trial revealed improved overall survival (OS) with a limited course of five cycles of tremelimumab added to durvalumab plus platinum chemotherapy. These post-hoc exploratory results, presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer, demonstrated improvement in the first-line treatment of patients with STK11, KEAP1, or KRAS-mutated Stage IV (metastatic) nonsmall-cell lung cancer (mNSCLC).

It has been noted that KRAS mutations are the most common tumor growth driver in NSCLC, which represents about 25% of patients. An estimated 6–15% of NSCLC is KEAP1-mutated and approximately 15% is KRAS-driven and STK11-mutated.

The analysis reported a hazard ratio (HR) of 0.56 for STK11-mutated non-squamous NSCLC, HR of 0.43 for KEAP1-mutated NSCLC, and 0.56 for KRAS-mutated non-squamous NSCLC. It was also determined that median OS and two-year survival rates across subgroups increased with the immunotherapy combination compared to chemotherapy. 

Both the STK11 and KRAS subgroup analyses were presented for patients with non-squamous histology. The KEAP1 subgroup analysis was presented for all mutation-evaluable patients regardless of tumor histology, due to the small sample size. 

This trial met key endpoints of progression-free survival (PFS) in 2019 and OS in 2021, reducing disease progression risk or death by 28% and death risk by 23% in patients with mNSCLC who were treated with first-line tremelimumab, durvalumab, and chemotherapy, compared to chemotherapy alone. 

Lead study investigator Melissa L. Johnson, MD, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute, concluded that, “Durvalumab and tremelimumab and chemotherapy represents a potential new first-line treatment option for metastatic [NSCLC].”




POSEIDON Phase III post-hoc exploratory analyses presented at WCLC 2022. AstraZeneca. Accessed October 17, 2022. 

Phase III POSEIDON Trial Shows Positive Results for Patients Taking Chemotherapy Plus Durvalumab and Tremelimumab. IASLC. Accessed October 17, 2022.