POSEIDON updates boost treatment potential of tremelimumab-durvalumab-CT for mNSCLC

In the updated analysis of the POSEIDON trial presented at ESMO 2022, the combination regimen comprising tremelimumab, durvalumab, and chemotherapy (T+D+CT) used in the first-line setting conferred long-term overall survival (OS) benefit in individuals with metastatic non-small-cell lung cancer (mNSCLC).

This phase III study comprised 1,013 patients with EGFR/ALK wild-type (wt) stage IV mNSCLC. Participants were randomized 1:1:1 to receive first-line durvalumab 1,500 mg + CT (Q3W up to four cycles) with or without a limited course of tremelimumab 75 mg, or platinum-based CT (Q3W up to six cycles). Following which, those receiving durvalumab were given durvalumab Q4W as maintenance therapy until disease progression, and optional pemetrexed Q4W. Participants were stratified by histology (non-squamous or squamous) and mutational status subgroups (STK11, KEAP1, KRAS). [ESMO 2022, abstract LBA59]

At a median follow-up of 46.5 months, T+D+CT continued to have an advantage over CT in terms of OS among censored patients (median 14.0 vs 11.7 months; hazard ratio [HR], 0.75). This finding aligns with the previously reported interim result (median follow-up 34.9 months) reflecting a statistically significant improvement in OS with T+D+CT vs CT (HR, 0.77; p=0.003). [J Thorac Oncol 2021:16(10_suppl):S844]

A quarter of patients receiving the T+D+CT regimen were alive at 3 years, as opposed to 14 percent in the CT arm. The OS benefit of T+D+CT was generally consistent across patient subgroups*.

In the non-squamous cohort, updated OS was longer with T+D+CT vs CT (median 17.2 vs 13.1 months; HR, 0.68). This treatment effect was more pronounced than that seen in the squamous cohort (median 10.4 vs 10.5 months; HR, 0.83).

When evaluating patients with non-squamous histology by mutation status, a trend for OS benefit in favour of T+D+CT over CT was seen among participants with STK11m** (median 15.0 vs 10.7 months; HR, 0.62). At 3 years, 26 percent of T+D+CT recipients were alive, which was markedly higher than the fraction of participants surviving in the CT arm (4 percent).

A similar OS trend favouring T+D+CT over CT was also observed among those with STK11wt (median 17.2 vs 13.4 months; HR, 0.70). In this subgroup, more patients on the combination regimen were alive at 3 years compared with those who were receiving CT (32 percent vs 20 percent).

T+D+CT continued to trump CT in participants with KEAP1 (median OS 13.7 vs 8.7 months; HR, 0.43 [m] and 14.0 vs 12.2 months; HR, 0.75 [wt]) and KRAS mutations (median OS 25.7 vs 10.4 months; HR, 0.55 and median 17.1 vs 14.4 months; HR, 0.78, respectively).

The incidence of serious adverse events (AEs) was higher with T+D+CT vs CT (28 percent vs 18 percent), but no new safety signals were identified based on the serious AEs collected during the long-term follow-up.

“[A]fter a median follow-up of approximately 4 years, [our findings] demonstrate the durable long-term OS benefit of adding a limited course of tremelimumab to durvalumab and four cycles of CT,” said the researchers.

“These data support the use of this regimen as a first-line treatment option for patients with mNSCLC, including harder-to-treat mutational subgroups such as STK11, KEAP1, or KRAS mutations,” they concluded.