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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. | LitMetric

AI Article Synopsis

  • - The POSEIDON study assessed the effectiveness of combining tremelimumab and durvalumab with chemotherapy in treating first-line metastatic non-small-cell lung cancer (mNSCLC) compared to standard chemotherapy alone.
  • - Results showed that the combination of durvalumab plus chemotherapy (D + CT) significantly improved progression-free survival (PFS), while the addition of tremelimumab (T + D + CT) offered even greater PFS and overall survival (OS) benefits.
  • - Despite improvement in outcomes, the study reported a similar rate of severe treatment-related adverse events across all treatment groups, with some patients needing to discontinue due to side effects, but overall the treatments were tolerable.

Article Abstract

Purpose: The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non-small-cell lung cancer (mNSCLC).

Methods: Patients (n = 1,013) with / wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT.

Results: PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; = .0009; median, 5.5 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; = .0758; median, 13.3 11.7 months; 24-month OS, 29.6% 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; = .0003; median, 6.2 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; = .0030; median, 14.0 11.7 months; 24-month OS, 32.9% 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events.

Conclusion: D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937097PMC
http://dx.doi.org/10.1200/JCO.22.00975DOI Listing

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