Marco Donia: 1L Ipi-Nivo in BRAF-Mutant Melanoma – Any Advantage of Targeted Therapy Induction?
Marco Donia, Research Group Leader of the TIL group at CCIT (Center for Cancer Immune Therapy) and Professor at the University of Copenhagen, shared a post on LinkedIn:
“First-line Ipi-Nivo in patients with BRAF-Mutant Melanoma: Any Advantage of Targeted Therapy Induction? (Lancet Oncology, Robert et al., June 2025)
The EBIN phase 2 trial (EORTC-sponsored) evaluated 12-week induction with encorafenib + binimetinib followed by ipilimumab + nivolumab, vs ipi+nivo alone, in patients with BRAFV600-mutant advanced melanoma. Patients with symptomatic or untreated brain metastases were excluded. Ipi/nivo used at 1+3 dose (not standard 3+1).
Key Points:
1. Efficacy: No PFS benefit from induction therapy (median PFS: 9 months both arms; HR 0.87; p=0.36)
2. Safety: Slightly higher grade 3–5 AEs with induction (42% vs 32%).
3. Potential signal of benefit in patients with very high LDH (>2x ULN); possible detriment in early-stage disease
Take-Home:
– Upfront immune checkpoint blockade remains standard, as shown in DREAMseq and SECOMBIT
– For patients with aggressive disease, induction targeted therapy is safe (per EBIN and SECOMBIT), but no evidence of superiority
– More data needed in high-LDH or liver metastases subgroups, potential advantage of induction with targeted therapy
– Still no solid data in symptomatic brain mets, only initial signals (e.g., MEMBRAINS)
Note: targeted therapy first may raise brain mets risk, see data from EBIN and SECOMBIT
Congratulations to all the authors and investigators for this important work!
Caroline Robert (Corresponding), Mario Mandalà, Paul Lorigan and Alexander van Akkooi.”
Title: Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced melanoma with BRAFV600E or BRAFV600K mutations (EBIN): an international, open-label, randomised, controlled, phase 2 study
Authors: Caroline Robert, Michal Kicinski, Caroline Dutriaux, Émilie Routier, Anne-Sophie Govaerts, Emanuel Bührer, Eve-Marie Neidhardt, Xavier Durando, Barouyr Baroudjian, Philippe Saiag, Caroline Gaudy-Marqueste, Paolo A Ascierto, Ana Arance, Michelangelo Russillo, Jean-Luc Perrot, Laurent Mortier, Francois Aubin, Stéphane Dalle, Florent Grange, Eva Muñoz-Couselo, Sorilla Mary-Prey, Mona Amini-Adle, Sandrine Mansard, Céleste Lebbe, Elisa Funck-Brentano, Sandrine Monestier, Alexander M M Eggermont, Felix Oppong, Leen Wijnen, Bastian Schilling, Mario MandalÁ, Paul Lorigan, Alexander C J van Akkooi
Read OncoDaily’s Special Article: Melanoma (Skin Cancer): Symptoms, Causes, Stages, Diagnosis and Treatment
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