Latest results from the Phase 3 POSEIDON trial (NCT03164616) demonstrate the use of tremelimumab (Imjudo), durvalumab (Darzalex), and chemotherapy as a first-line combination approach in patients with more challenging metastatic non-small cell lung cancer Supports the use of therapy alone. -Subgroup to be treated.Results include analysis by non-squamous or squamous histology; STK11, KEAP1or class Mutation status for mutation-positive or wild-type disease. Her one-year follow-up data were presented by Solange Peters, MD, at the European Society of Medical Oncology (ESMO) Immuno-Oncology Congress 2023.
“After a median follow-up of more than 5 years, [POSEIDON] Demonstrates durable long-term overall survival [OS] advantage [when] We are adding a limited course of tremelimumab and durvalumab,” said Peters, professor of oncology and head of the medical oncology and thoracic malignancies program at Lausanne University Hospital in Switzerland. “for 5 years [OS] rate [for the triplet] 15.7% vs. 6.8%, more than twice as high as chemotherapy,” Peters continued.
In POSEIDON, 1,013 patients were randomly assigned to three arms. Tremelimumab + durvalumab + chemotherapy (arm 1). Durvalumab and chemotherapy (arm 2). or chemotherapy alone arm (Arm 3). Dosing schedules were 4 cycles every 3 weeks, 4 cycles every 3 weeks, and up to 6 cycles every 3 weeks, respectively. Patients in arm 1 received tremelimumab only at her 16th week and durvalumab every 4 weeks until disease progression. For the patient in arm 2, he received durvalumab every 4 weeks until disease progression.
Eligible patients had an ECOG performance status of 0 or 1; EGFR or alk He was wild type and had no history of treatment for metastatic disease. “Patients were stratified according to PD-L1 expression, disease stage, and histology,” Peters said. “Contains pre-specified long-term tracking endpoints” [OS] and serious adverse events. [AEs],” she added.
The researchers found that the long-term OS benefit comparing triplet combination therapy to chemotherapy alone showed a greater benefit in patients with non-squamous histology, with an HR of 0.69 and a 5-year OS rate of 20.5% vs. 9.1%. He pointed out that there is.
In populations where mutations can be assessed, 30% class mutations (n = 37), 6% KEAP1 mutations (n = 37); STK11 Mutations (n = 87).
The updated OS is STK11 Due to the mutation, median OS for patients treated with the triplet regimen was 15.0 months (HR, 0.57; 95% CI, 0.32-1.04) compared with 6.9 months for patients treated with durvalumab and chemotherapy ( HR, 1.02, 95% CI, 0.59). -1.80) and 10.7 months (95% CI, 6.0-14.9) for patients treated with chemotherapy alone. The OS benefit was maintained with his triple combination therapy in patients with: STK11 The HR for the mutation was 0.57 and the 5-year OS rate was 12.9% and 0% for the chemotherapy regimen.
The updated OS is KEAP1 Mutation status across all histology showed that the triplet regimen maintained an OS advantage with an HR of 0.43.for patients KEAP1 With mutations, median OS for patients treated with triplet was 13.7 months (HR, 0.43; 95% CI, 0.16-1.25) and median OS for patients treated with doublet was 8.1 months (HR, 0.77; 95% CI). , 0.31-2.15), and the median OS for patients who received chemotherapy was only 8.7 months.
for patients class In the presence of mutations, the sustained OS advantage with the triplet regimen compared with chemotherapy alone was 0.55 OS and 5-year OS rate of 21.7% versus 8.1%, respectively.
table1 shows subsequent systemic anticancer therapy by regimen group. “In the chemotherapy-alone group, 63% of patients received more or less immunotherapy. [than] I then started treatment in the immunotherapy department,” Peters said.
Serious adverse events (SAEs), including AEs leading to death, were collected during long-term follow-up. No other safety data were collected after the final analysis of OS superiority. Since the final analysis, seven additional patients experienced her SAEs (one considered treatment-related) and four additional patients experienced AEs leading to death (not treatment-related).
“Across patient subgroups, long-term overall survival benefits were generally consistent with the intention-to-treat population,” Peters said. “Consistent with previous analyses, the addition of tremelimumab to durvalumab and chemotherapy conferred an overall survival benefit regardless of PD-L1 expression,” he concluded Dr. Peters.
