Prof. Scott Kopetz (MD Anderson Cancer Center, Houston, USA) presented the international collaboration, which included >200 centres worldwide in this open label, three-arm randomised clinical trial. A total of 665 patients with BRAF V600E-mutant mCRC who had progressed after one or two prior regimens in the metastatic setting were randomised to receive triplet therapy, doublet therapy (encorafenib and cetuximab), or the investigator’s choice of irinotecan or folinic acid, fluorouracil and irinotecan (FOLFIRI) and cetuximab [1]. BRAF mutations are estimated to occur in up to 15% of patients with mCRC, with V600E being the most common mutation and representing a poor prognosis for these patients.
The treatment combination resulted in median OS of 9 months (95% CI 8-11.4) for the triplet combination therapy compared with 5.4 months (95% CI 4.8-6.6) for current standard-of-care (HR 0.52; 95% CI 0.39-0.7, P<0.0001). Objective response rate (ORR) for the triplet-targeted therapy was 26% (95% CI 18-35) compared with just 2% (95% CI 0-7; P<0.0001) for standard therapy.
Median OS for the doublet combination was 8.4 months (95% CI 7.5-11) compared with standard therapy (HR 0.6; 95% CI 0.45-0.79; P<0.0003). The study was not powered to compare triplet and doublet therapies, but future analyses will explore which patients are most likely to benefit from triplet vs doublet combinations.
BRAF V600E targeted treatment was well tolerated, with grade 3 or higher adverse events seen in 58% of patients on triplet treatment, 50% of those in the doublet group, and 61% of those in the standard therapy group.
In conclusion, BEACON CRC is the first and only phase 3 trial designed to test BRAF/MEK combination targeted therapies in patients with mCRC and the BRAF V600E mutation, and the study reported clinical benefit for those selected patients. An ongoing study (ANCHOR-CRC) is evaluating the effect of triplet therapy in BRAF-mutant mCRC.
1. Kopetz S et al. ESMO Congress 2019. Abstract LBA006.
2. Kopetz S et al, N Engl J Med. 2019 Oct 24;381(17):1632-1643.
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Table of Contents: ESMO 2019
Featured articles
Interview with ESMO President Prof. Josep Tabernero
Breast Cancer
Triple negative breast cancer gets positive news: KEYNOTE-522 interim results
CDK4/6 inhibitors change landscape of breast cancer treatment: 2 studies
Veliparib-chemo combo prolongs survival without disease progression in some advanced breast cancer patients
Lung Cancer
Improved response rates without survival benefit with pembrolizumab in pretreated mesothelioma
Frontline ipilimumab/nivolumab improves OS in advanced NCLSC
First-line osimertinib significantly lengthens OS in NSCLC
Liquid biopsy to decide the best treatment for NSCLC
Melanoma
Long-term data from CheckMate 067
Adjuvant nivolumab provides benefit
Nivolumab+ipilimumab superior to monotherapy for melanoma brain metastases
GI Cancers
Preoperative chemotherapy for colon cancer
Nivolumab improves OS in advanced oesophageal cancer
Liquid biopsy identifies relapse in patients with colorectal cancer after surgery
In hepatocellular carcinoma, CheckMate 459 misses OS endpoint, but some interesting trends emerge
Heavily pre-treated GIST: ripretinib improves PFS
FGFR2+ cholangiocarcinoma: pemigatinib active as second-line treatment
IDH1+ cholangiocarcinoma: phase 3 results show improved PFS
Advanced colorectal cancer and BRAF mutations: triplet combination improves survival
Genitourinary Cancers
25% reduction in the risk of death in patients with nmCRPC treated with apalutamide
Enfortumab vedotin and pembrolizumab in advanced bladder cancer: initial results
PARP inhibition in selected patients slows progression on advanced prostate cancer
PFS extension with immunotherapy + chemotherapy in urothelial cancer
Third-line in mCRPC: CARD trial
Prostate cancer: spare radiotherapy after surgery
Novel mode of action for kidney cancer treatment
Gynaecological Cancers
Ovarian cancer patients benefit from combined maintenance therapy
Combination of PARP inhibition plus chemotherapy in ovarian cancer
PFS benefit with niraparib as first-line maintenance in ovarian cancer
CNS Tumours
Ceritinib in ALK+ NSCLC brain metastases
Solid Tumours/Pan-Tumour Data
Mixed data: AMG 510 in tumours with KRASG12C
DNA profiling of carcinoma of unknown primary should inform treatment
Larotrectinib: safe and effective in TRK fusion-positive tumours
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