POSEIDON: Novel option for harder-to-treat subgroups of patients with metastatic NSCLC?

An exploratory analysis of the phase 3 POSEIDON trial showed that first-line treatment with tremelimumab plus durvalumab plus chemotherapy was efficacious in subgroups of patients with metastatic non-small cell lung cancer (NSCLC) that are usually associated with poor responses to immunotherapy, including those with KEAP1, KRAS, and STK11 mutations [1].

In patients with EGFR/ALK wildtype metastatic NSCLC, the combination of tremelimumab, durvalumab, and chemotherapy outperformed chemotherapy alone regarding progression-free survival (PFS) and overall survival (OS), primary results from the phase 3 POSEIDON trial (NCT03164616) displayed (n=1,003) [2]. However, it was unknown whether this combination treatment was beneficial for patients with STK11, KEAP1, or KRAS mutations. Therefore, Prof. Solange Peters (Lausanne University, Switzerland) and co-investigators performed an exploratory analysis of outcomes from the POSEIDON trial by mutational status.

Participants with STK11 mutations appeared to have an OS benefit if they were treated with the experimental treatment (n=31) instead of chemotherapy alone (n=22; median OS 15.0 vs 10.7 months; HR 0.56; 95% CI 0.56–1.03). Similarly, there was a clear trend towards an OS benefit of the experimental treatment over chemotherapy alone in those with KEAP1 mutations (median OS 13.7 vs 8.7 months; HR 0.43; 95% CI 0.16–1.25). However, the sample size of patients with KEAP1 mutations was small, with only 22 patients who followed the experimental treatment and 6 patients who received chemotherapy alone. Furthermore, patients with KRAS-mutated non-squamous cell histology had a longer median OS if they received tremelimumab, durvalumab, and chemotherapy (n=60) than if they received chemotherapy alone (n=53; median OS 25.7 vs 10.4 months; HR 0.56; 95% CI 0.36–0.88). PFS data and objective response rates demonstrated similar trends of efficacy in these subgroups.

According to Prof. Peters, this data suggests that the combination therapy of tremelimumab, durvalumab, and chemotherapy is as a potential first-line treatment for harder-to-treat subgroups of patients with metastatic NSCLC.

1. Peters S, et al. Association between KRAS/STK11/KEAP1 mutations and outcomes in POSEIDON: durvalumab ± tremelimumab + chemotherapy in mNSCLC. OA15.04, WCLC 2022, Vienna, Austria, 06–09 August.
2. Johnson M, et al. PL02.01, WCLC 2021, 08–14 September.

 

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Posted on 23 August 202223 August 2022