Impact of encorafenib on survival of patients with BRAFV600E-mutant metastatic colorectal cancer in a real-world setting

M Zurloh; M Goetz; T Herold; J Treckmann; P Markus; B Schumacher; D Albers; A Rink; V Rosery; G Zaun; K Kostbade; M Pogorzelski; S Ting; H Schmidt; R Stiens; M Wiesweg; M Schuler; Stefan Kasper; I Virchow

doi:10.1007/s00432-023-05141-y

Impact of encorafenib on survival of patients with BRAF^V600E-mutant metastatic colorectal cancer in a real-world setting

J Cancer Res Clin Oncol. 2023 Nov;149(14):12903-12912. doi: 10.1007/s00432-023-05141-y. Epub 2023 Jul 19.

Authors

M Zurloh^{1

2}, M Goetz³, T Herold^{3

4

2}, J Treckmann^{5

2}, P Markus⁶, B Schumacher⁷, D Albers⁷, A Rink^{5

2}, V Rosery^{1

2}, G Zaun^{1

2}, K Kostbade^{1

2}, M Pogorzelski^{1

2}, S Ting^{3

8}, H Schmidt^{9

2}, R Stiens^{1

2}, M Wiesweg^{1

4

2}, M Schuler^{1

4

2}, Stefan Kasper^{10

11

12}, I Virchow^{1

2}

Affiliations

¹ Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
² Medical Faculty, University Duisburg-Essen, Essen, Germany.
³ West German Cancer Center, Institute of Pathology Essen, University Hospital Essen, Essen, Germany.
⁴ German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
⁵ West German Cancer Center, Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany.
⁶ Department of General Surgery and Traumatology, Elisabeth Hospital, Essen, Germany.
⁷ Department of Gastroenterology, Elisabeth Hospital, Essen, Germany.
⁸ Institute of Pathology Nordhessen, Kassel, Germany.
⁹ Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital Essen, Essen, Germany.
¹⁰ Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany. stefan.kasper-virchow@uk-essen.de.
¹¹ German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. stefan.kasper-virchow@uk-essen.de.
¹² Medical Faculty, University Duisburg-Essen, Essen, Germany. stefan.kasper-virchow@uk-essen.de.

Abstract

Purpose: Patients with BRAF^V600E-mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with BRAF^V600E-mutant mCRC to retrieve the best treatment strategy.

Patients and methods: Clinico-pathological data were extracted from the electronic health records. Kaplan-Meier method was used to estimate overall (OS) and progression-free survival (PFS). Objective response rate (ORR) was assessed according to RECIST 1.1.

Results: In total, 51 patients were enrolled. FOLFOXIRI was administered to 12 patients; 29 patients received FOLFOX or FOLFIRI as first-line treatment. Median OS was 17.6 months. Median PFS with FOLFOXIRI (13.0 months) was significantly prolonged (HR 0.325) as compared to FOLFOX/FOLFIRI (4.3 months). However, this failed to translate into an OS benefit (p = 0.433). Interestingly, addition of a monoclonal antibody to chemotherapy associated with superior OS (HR 0.523). A total of 64.7% patients received further-line therapy, which included a BRAF inhibitor in 17 patients. Targeted therapy associated with very favourable OS (25.1 months).

Conclusion: Patients with BRAF^V600E-mutated mCRC benefit from the addition of an antibody to first-line chemotherapy. Further-line treatment including a BRAF inhibitor has a dramatic impact on survival.

Keywords: BRAFV600E; Chemotherapy; Encorafenib; Metastatic colorectal cancer.