Amol Akhade/hiranandanihospital.org
May 31, 2025, 18:56
Amol Akhade: BREAKWATER Trial at ASCO 2025 – Raising the Bar in BRAF V600E–Mutant mCRC?
Amol Akhade, Consultant Medical Oncologist at the Suyog Cancer Clinics, shared a post on LinkedIn:
“BREAKWATER Trial at ASCO 2025: Raising the Bar in BRAF V600E–Mutant mCRC?
The BREAKWATER Phase 3 trial (NCT04607421) delivered a bold message at ASCO25:
Can we improve survival outcomes in the historically poor-prognosis population of BRAF V600E–mutant metastatic colorectal cancer (mCRC)?
Answer: Yes—but with caveats.
Trial Design
637 patients were randomized to:EC: Encorafenib + Cetuximab EC + mFOLFOX6 SOC: Standard chemo ± bevacizumab
Primary Results (EC+mFOLFOX6 vs SOC)
PFS: 12.8 vs 7.1 months | HR 0.53
OS: 30.3 vs 15.1 months | HR 0.49
ORR: 65.7% vs 37.4%
DoR ≥12 months: 34.8% vs 17.6%
These are arguably the best outcomes ever seen in this molecular subtype. The FDA’s earlier accelerated approval of EC+mFOLFOX6 was based on ORR; this survival data adds weight to its adoption in 1L.
But here’s where nuance matters:
The trial was open-label, and the EC arm was closed early, making 3-arm comparisons tricky.
The SOC arm was heterogeneous (± Bev), limiting global applicability.
Toxicity was non-trivial—Grade 3+ events in 46% of EC+mFOLFOX6 patients.
No data on QoL or PROs, which is vital in a metastatic setting.
BRAF V600E remains a small subset (~8–10%) of mCRC—this isn’t a universal solution.
So how should we interpret this?
For fit patients, EC+mFOLFOX6 is a legitimate new standard. For frailer patients, EC alone (OS: 19.5 mo) remains reasonable. For the field, this is an important practice-changer, but not without important clinical judgment.
What do you think? Is EC+mFOLFOX6 ready to be the new SOC in your practice? Or do we still need more real-world and QoL data before a full shift?”
More posts featuring ASCO25.
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Challenging the Status Quo in Colorectal Cancer 2024
December 6-8, 2024
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ESMO 2024 Congress
September 13-17, 2024
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ASCO Annual Meeting
May 30 - June 4, 2024
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Yvonne Award 2024
May 31, 2024
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OncoThon 2024, Online
Feb. 15, 2024
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Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023