Patients with metastatic non-small cell lung cancer (NSCLC) who received a combined therapy of tremelimumab, durvalumab, and chemotherapy experienced longer overall survival (OS) compared to patients who received chemotherapy alone, regardless of STK11, KEAP1, or KRAS mutational status, according to research (abstract 1220) from the POSEIDON trial presented at IASLC’s 2022 World Conference on Lung Cancer.
Presenter Solange Peters, MD, PhD, who is head of the medical oncology service and chair of thoracic oncology at Lausanne University, Switzerland, and her research colleagues conducted an exploratory analysis of survival outcomes in POSEIDON according to KRAS, STK11, and KEAP1 mutational status.
The analysis showed mutations in STK11 and KEAP1 correlate with poor prognosis and are associated with chemorefractory and immunologically “cold” tumors that are less responsive to therapy. KRAS-mutant NSCLC is heterogenous and frequently co-mutated with STK11 and/or KEAP1.
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Dr. Peters and her colleagues randomized 1,013 patients (1:1:1) to first-line tremelimumab, durvalumab, and chemotherapy; durvalumab and chemotherapy; or chemotherapy alone, with stratification by tumor cell PD-L1 expression (≥50% vs. <50%), disease stage (IVA vs. IVB), and histology (squamous vs. non-squamous). Patient tumors were molecularly characterized via sequencing of tumor tissue DNA and/or circulating tumor DNA samples. Progression-free survival (PFS) and OS outcomes were analyzed in patients with or without functional mutations in KRAS, STK11, or KEAP1.
The mutation-evaluable non-squamous NSCLC population included 612 patients (96% of the intention-to-treat non-squamous population) whose tumors were molecularly characterized; 30%, 14%, and 6% had KRAS, STK11, and KEAP1 mutations, respectively. OS hazard ratios favored patients in the tremelimumab, durvalumab, and chemotherapy arm versus chemotherapy alone, irrespective of KRAS, STK11, or KEAP1 mutational status, consistent with results in the ITT population.
“Notably, landmark 24-month overall survival rates were higher with tremelimumab, durvalumab, and chemotherapy versus chemotherapy across all subgroups, including those with KRAS, STK11, and KEAP1 mutations, suggesting sustained benefit with the triplet regimen,” Dr. Peters said. “Our analysis supports using combined therapy of tremelimumab, durvalumab, and chemotherapy as a potential first-line treatment option for patients with metastatic NSCLC, including those with KRAS, STK11, or KEAP1 tumors.”
In previously reported results of the phase 3 POSEIDON trial, patients with EGFR/ALK wild-type metastatic NSCLC who were given first-line tremelimumab, durvalumab, and chemotherapy demonstrated statistically significant improvements in both PFS and OS versus chemotherapy alone.
