POSEIDON update confirms OS benefit of tremelimumab/durvalumab plus chemotherapy in mNSCLC

Based on Phase 3 POSEIDON trial (NCT03164616) Prespecified5-year overall survival update results announced in 2023, in first-line Durvalum A limited course of tremelimumab/tremelimumab in addition to ab and chemotherapy provides a sustained overall survival (OS) benefit compared with chemotherapy in patients with previously untreated metastatic non-small cell lung cancer.

At a median follow-up of 63.4 months (range 0.0-73.9), patients who received tremelimumab/chemotherapy/durvalumab (n=338) had a median OS of 14.0 months (95% CI: 11.7-16.1), while patients who received chemotherapy alone had a median OS of 11.0 months. At 6 months (95% CI: 10.5-13.1) (n = 337; HR, 0.76; 95% CI, 0.64-0.89), the 5-year OS rates were 15.7% and 6.8%, respectively. Additionally, in the cohort of patients who received durvalumab/chemotherapy (n=338), the median OS was 13.3 months (95% CI, 11.4-14.7), and the 5-year OS rate was 13.0%. Compared with chemotherapy alone, the hazard ratio was 0.84 (95% CI: 0.72-1.00).

POSIEDON enrolled 1,013 patients with EGFR or ALK wild-type stage IV NSCLC and ECOG performance status 0 or 1 who had not received prior treatment for metastatic disease and had tumor biopsies and baseline plasma samples for circulating tumor DNA (CT DNA) analysis. Patients were stratified based on PD-L1 expression (≥50% tumor cells vs <50%), histology (nonsquamous vs squamous), and disease stage (IVA vs IVB). Patients were randomized 1:1:1 to receive durvalumab/limited-course tremelimumab/chemotherapy every 3 weeks for 4 cycles, followed by only 1 additional dose of post-chemotherapy tremelimumab at week 16 and durvalu every 4 weeks. mab maintenance therapy until disease progression (PD), with options to receive pemetrexed every 4 weeks; durvalumab/chemotherapy every 3 weeks for 4 cycles, then durvalumab monotherapy every 4 weeks until PD; or platinum-based chemotherapy every 3 weeks for up to 6 cycles. Durvalumab is administered at a dosage of 1500 mg, and tremelimumab is administered at a dosage of 75 mg.

fromPOSEIDON’s data show that compared with chemotherapy alone, tremelimumabcombinationdurvalumab/chemotherapy is effective in the first-line treatment of patients with metastatic non-small cell lung cancer. The improvements in progression survival (PFS) and OS were statistically significant, with hazard ratios of 0.72 (95% CI: 0.60-0.86; p = 0.0003) and 0.77 (95% CI: 0.65-0.92; p = 0.0030) respectively. In addition, durvalumab plus chemotherapy provided a significant PFS benefit compared with chemotherapy alone (HR, 0.74; 95% CI: 0.62-0.89; P0.0009). Although the data did not reach statistical significance, the combination was associated with a positive trend toward improved OS (HR, 0.86; 95% CI: 0.72-1.02; P=0.0758).

Long-term OS benefit of tremelimumab/durvalumab/chemotherapy (n=214) compared with chemotherapy alone(n=214) in non-squamous The group of patients with cellular diseases was larger, with median OS of 17.2 months (95% CI, 14.9-21.8) and 13.0 months (95% CI, 10.6-15.1) (HR, 0.81; 95% CI, 0.66-1.00), the 5-year OS rates were 20.5% and 9.1% respectively. In the cohort of patients with non-squamous cell disease who received durvalumab/chemotherapy (n=209), median OS was 14.8 months (95% CI, 11.8-18.3); compared with patients who received chemotherapy alone, the HR was 0.81 (95% CI: 0.66-1.00). The 5-year overall survival rate of durvalumab combined with chemotherapy was 16.4%.

In the tremelimumab plus durvalumab/chemotherapy, durvalumab/chemotherapy, and chemotherapy alone groups, the incidence of evaluable serious all-cause adverse reactions (AEs) was 45.8%, 40.7%, and 35.1%, respectively. In these populations, all-cause AEs resulted in death in 13.0%, 10.8%, and 9.0% of patients, respectively. Treatment-related serious AEs occurred in 27.6%, 19.8%, and 17.7% of patients, respectively. The incidence of treatment-related AEs leading to death was 3.3%, 2.1%, and 2.4%, respectively. Since the final analysis, seven additional patients experienced serious AEs, including one serious AE that was considered treatment-related. In addition, 4 additional patients experienced AEs leading to death, none of which were determined to be treatment-related.

These results support the use of tremelimumab plus durvalumab plus chemotherapy as a first-line treatment option for patients with non-small cell lung cancer, including what we call a difficult-to-treat subgroup. Based on these findings, the ongoing Phase 3 TRITON trial is evaluating durvalumab/tremelimumab/chemistry in combination with pembrolizumab chemotherapy in patients with non-small cell lung cancer.