The SECOMBIT trial

During an ESMO presentation, Prof. Paolo Ascierto, a medical oncologist at the National Cancer Institute of Naples, Italy, provided a 5-year update on the SECOMBIT study, focusing on total PFS, OS, and brain metastasis-free survival. The SECOMBIT study is a phase II randomised trial that explored different sequences of targeted therapy for patients with BRAFV600-mutant melanoma in the metastatic setting. The study examined three sequences:

Arm A: encorafenib plus binimetinib until progressive disease (PD) -> ipilimumab plus nivolumab -> Nivolumab.

Arm B: ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib.

Arm C (‘sandwich arm’): encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib.

The median follow-up period was 56 months. The findings at the five-year mark affirmed previous results, demonstrating that initiating immunotherapy first is more effective than commencing with targeted therapy. Total PFS at five years was 50% for arms B and C, compared to 27% for arm A. In terms of OS, arms B and C showed superior results, although arm A showed some recovery. Subgroup analysis of patients with elevated LDH, indicative of a high tumour burden, revealed a substantial benefit for the sandwich arm. In this group, 60% of patients were still alive at 5 years, in contrast to 15% in arm A. This indicates that initiating treatment with encorafenib plus binimetinib for two months before transitioning to immunotherapy could be crucial in targeting the tumour effectively.

Prof. Ascierto also presented new data on brain metastasis-free survival, addressing the open question of which treatment might better protect against the development of new brain metastases. Interestingly, both the sandwich arm and arm B demonstrated brain metastasis-free survival rates of 85% and 80%, respectively, compared to 56% in arm A. These findings suggest that immunotherapy may provide protection against the occurrence of new brain metastases. A biomarker analysis indicated that patients with high tumour mutational burden (TMB) and those with JAK mutations experienced better brain metastasis-free survival, with 92% of patients being free of brain metastases at 5 years.

In summary, commencing treatment with immunotherapy appears to be a more effective strategy and may also offer protection against the development of new brain metastases for patients with BRAFV600-mutant melanoma.