ROAR-BTC

NCT02034110 📎

Regimen

Experimental
Dabrafenib 150 mg PO BID + trametinib 2 mg PO QD (BRAF V600E inhibitor + MEK inhibitor combination)
Control
single-arm / no comparator

Population

BRAF V600E-mutated unresectable or metastatic BTC; BTC cohort n=43 (ICC predominantly ~85%, with ECC ~10%, GBC ~5%). BRAF V600E occurs in ~3-5% ICC, rare in other BTC subtypes. All patients had ≥1 prior therapy. BRAF V600E detected by local molecular testing. ROAR is a multi-cohort basket trial; the BTC cohort was published as part of the primary BTC analysis (Subbiah V, Lancet Oncol 2020).

Key finding

Dabrafenib + trametinib achieved ORR 51% in BRAF V600E-mutated BTC — among the highest response rates observed in any BTC biomarker cohort. FDA granted accelerated approval for dab+tram in BRAF V600E-mutated solid tumors (tumor-agnostic, 2022) covering BTC. BRAF V600E mutation is rare (~3-5% ICC) but the high ORR means this signal strongly justifies testing. The combination is well-established from melanoma and NSCLC, facilitating rapid adoption once the mutation is identified. Pyrexia and rash are class-effect toxicities.

Source: PMID 32818466

Timeline

    Guideline citations

    • NCCN BTC (p.34)