Updated results of SECOMBIT trial

First OS data of the SECOMBIT trial did not (yet) show the optimum sequential approach with immunotherapy and targeted therapy in patients with BRAF-mutated metastatic melanoma.

Treatment with targeted therapy (BRAF and MEK inhibitors) and immune-checkpoint inhibitors (anti-CTLA4, anti-PD-1) have improved the outcome of BRAF-mutated metastatic melanoma patients in first line, but the best sequencing remains an open question. In the SECOMBIT trial (NCT02631447) immunotherapy and targeted therapy were given sequentially [1]. This phase 2 study included 251 patients with untreated, metastatic BRAF-mutated melanoma, who were randomised 1:1:1 to 3 arms: encorafenib plus binimetinib until progression, followed by ipilimumab plus nivolumab (arm A); ipilimumab plus nivolumab until progression, followed by encorafenib plus binimetinib (arm B); or encorafenib plus binimetinib for 8 weeks, followed by ipilimumab plus nivolumab until progression, followed by encorafenib plus binimetinib (arm C). Primary endpoint of SECOMBIT is overall survival (OS), secondary endpoints are total PFS, PFS until second progression, and best ORR. First results (median PFS) of SECOMBIT were presented at ESMO 2020 [1]. Prof. Paolo Ascierto (Istituto Nazionale Tumori "Fondazione Pascale", Italy) presented updated results [2].

The study primary endpoint was met in each arm, with at least 30 patients alive at 24 months; median OS was not reached in any of the treatment arms. The survival rate at 2 and 3 years was 65% and 54% in arm A, 73% and 62% in arm B, and 69% and 60% in arm C, respectively. Total PFS rate at 2 and 3 years was 46% and 41% in arm A, 65% and 53% in arm B, and 57% and 54% in arm C.

“With a median follow-up of 32.2 months, 2- and 3-year rates of both total PFS and OS show a better trend in arm B and C,” concluded Prof. Ascierto. “Longer follow-up is required to better define the data and monitor the trend. In addition, biomarkers analysis is ongoing.”

1. Ascierto PA, et al. ESMO 2020 Virtual Meeting, abstract LBA45, 19–21 Sep.


2. Ascierto PA, et al. SECOMBIT: The best sequential approach with combo immunotherapy [ipilimumab (I) /nivolumab (N)] and combo target therapy [encorafenib (E)/binimetinib (B)] in patients with BRAF mutated metastatic melanoma: A phase II randomized study. Abstract LBA40, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 2021