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Durvalumab ± Tremelimumab + Chemo Shows Promise in LC

December, 12, 2023 | Lung Cancer, NSCLC (Non-Small Cell Lung Cancer)

KEY TAKEAWAYS

  • The POSEIDON phase III trial aimed to evaluate long-term OS outcomes following a median follow-up period exceeding 5 years.
  • Long-term data confirmed the approved combo (T+D+CT) offers lasting survival benefits in early-stage lung cancer, even for patients with less responsive tumors.

In a major lung cancer study (POSEIDON), combining chemotherapy(chemo) + two immunotherapies-tremelimumab and durvalumab(T+D+CT), extended both progression-free survival(PFS) and overall survival(OS) compared to chemo alone.

This powerful option, effective even in difficult cases, is now approved as a first-line treatment. Adding a second immunotherapy (T) showed less benefit for OS, suggesting further research into optimizing immunotherapy combinations. So, for a study, researchers aimed to evaluate long-term OS outcomes following a median follow-up period exceeding 5 years.

About 1,013 patients were assigned in a 1:1:1 ratio to receive first-line treatment with D( until progression) ± limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles) or CT alone (up to 6 cycles). 

Stratification factors included tumor cell (TC) PD-L1 expression (TC ≥50% vs <50%; VENTANA PD-L1 [SP263] assay), disease stage (IVA vs IVB), and histology (squamous vs NSQ). The prespecified long-term follow-up analysis focused on OS. Serious adverse events were monitored throughout the extended follow-up period.

The result demonstrated sustained OS benefits compared to CT alone (HR 0.76; 95% CI 0.64–0.89) in updated data as of August 24, 2023 (median FU 63.4 mo in censored pts). The 5-year OS rates were 15.7% vs 6.8%. The OS improvement with D+CT vs CT was of a lesser magnitude (HR 0.84; 95% CI 0.72–1.00; 5-year OS 13.0%). 

Updated results indicated that the OS benefit with T+D+CT vs CT continued to be more pronounced in patients with non-squamous (NSQ) vs squamous histology (data to be presented). Consistent with earlier analyses, OS benefit was maintained with T+D+CT (but not D+CT) vs CT in patients with PD-L1 TC <1%. Analysis of OS by STK11/KEAP1/KRAS mutation status is yet to be presented. No new safety signals were identified.

The study confirmed the approved combo (T+D+CT) offers lasting survival benefits in early-stage lung cancer, even for patients with less responsive tumors.

Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/23 

Clinical Trial: https://clinicaltrials.gov/study/NCT03164616 

Peters S. LBA3 – Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in first-line metastatic (m) NSCLC: 5-year overall survival (OS) update from the POSEIDON study. Presented at ESMO IO 2023. LBA3. Lausanne, Switzerland.

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