KEY TAKEAWAYS
- The phase III POSEIDON trial evaluated T + D + CT and D + CT compared to alone CT for first-line treatment of mNSCLC.
- The study’s primary aim was to assess the efficacy of T + D + CT and D + CT in improving PFS and OS compared to CT alone.
- The study randomly assigned 1,013 mNSCLC patients without EGFR/ALK mutations to one of three treatment groups and monitored them for PFS and OS.
- Adding a restricted T + D + CT regimen significantly improved PFS and OS compared to CT alone, while D + CT improved PFS considerably.
- The incidence of grade 3/4 treatment-related adverse events was observed in 51.8%, 44.6%, and 44.4% of patients who received T + D + CT, D + CT, and CT.
- The combination of D and CT demonstrated a statistically significant improvement in PFS compared to CT alone, while the addition of T to D and CT was substantial.
The POSEIDON study, a phase III open-label trial, assessed the efficacy of tremelimumab in combination with durvalumab and chemotherapy (T + D + CT) and durvalumab in combination with chemotherapy (D + CT) compared to chemotherapy alone (CT) as a first-line treatment for metastatic non-small-cell lung cancer (mNSCLC). In this clinical trial, 1,013 patients diagnosed with metastatic non-small cell lung cancer and who tested negative for EGFR/ALK mutations were randomly assigned to one of three treatment groups. The first group received tremelimumab 75 mg in combination with durvalumab 1,500 mg and platinum-based chemotherapy for a maximum of four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression and one additional dose of tremelimumab. The second group received durvalumab in combination with chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression. The third group received chemotherapy for up to six 21-day cycles, with or without maintenance pemetrexed, and served as the control group. The study’s primary endpoints were progression-free survival (PFS) and overall survival (OS) for the combination of the investigational drug and chemotherapy compared to chemotherapy alone. The study’s primary endpoints were PFS and OS for the treatment group receiving the combination of targeted therapy, chemotherapy, and immunotherapy compared to the group receiving only chemotherapy.
The PFS was significantly enhanced with the combination of D and CT compared to CT alone, as evidenced by a hazard ratio (HR) of 0.74, a 95% confidence interval (CI) ranging from 0.62 to 0.89, and a P=0.0009. The median PFS was 5.5 months for the D + CT group and 4.8 months for the CT group. Although there was a trend for improved overall survival (OS), it did not reach statistical significance, with an HR of 0.86, a 95% CI of 0.72 to 1.02, and a P=0.0758. The median OS was 13.3 months for the D + CT group and 11.7 months for the CT group, with a 24-month OS of 29.6% for the D + CT group and 22.1% for the CT group. The study results indicated that the combination of T + D + CT significantly improved progression-free survival (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and overall survival (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) compared to CT alone. The incidence of treatment-related adverse events of maximum grade 3/4 was observed in 51.8%, 44.6%, and 44.4% of patients who received T + D + CT, D + CT, and CT, respectively: 15.5%, 14.1%, and 9.9% of patients discontinued treatment due to treatment-related adverse events. The combination of D and CT demonstrated a statistically significant improvement in progression-free survival (PFS) compared to CT alone. Adding a restricted regimen of tremelimumab to durvalumab and chemotherapy resulted in a substantial improvement in overall survival and progression-free survival compared to chemotherapy alone, with no significant increase in adverse effects. This may offer a promising alternative for first-line metastatic non-small cell lung cancer treatment.
Source:https://pubmed.ncbi.nlm.nih.gov/36327426/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03164616
Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, Kim SW, Ursol G, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Shi X, Poole L, Peters S, Garon EB, Mok T; POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. doi: 10.1200/JCO.22.00975. Epub 2022 Nov 3. PMID: 36327426; PMCID: PMC9937097.
