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Clinical Trial
. 2023 May 10;41(14):2628-2637.
doi: 10.1200/JCO.22.01693. Epub 2023 Feb 10.

ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer

Eric Van Cutsem  1 , Julien Taieb  2 , Rona Yaeger  3 , Takayuki Yoshino  4 , Axel Grothey  5 , Evaristo Maiello  6 , Elena Elez  7 , Jeroen Dekervel  1 , Paul Ross  8 , Ana Ruiz-Casado  9 , Janet Graham  10 , Takeshi Kato  11 , Jose C Ruffinelli  12 , Thierry André  13 , Edith Carrière Roussel  14 , Isabelle Klauck  15 , Mélanie Groc  14 , Jean-Claude Vedovato  14 , Josep Tabernero  16
Affiliations
Clinical Trial

ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer

Eric Van Cutsem et al. J Clin Oncol. .

Abstract

Purpose: The positive BEACON colorectal cancer (CRC) safety lead-in, evaluating encorafenib + cetuximab + binimetinib in previously treated patients with BRAFV600E-mutated metastatic CRC (mCRC), prompted the design of the phase II ANCHOR CRC study (ClinicalTrails.gov identifier: NCT03693170). ANCHOR CRC aimed to evaluate efficacy, safety, and quality of life with first-line encorafenib + binimetinib + cetuximab in BRAFV600E-mutated mCRC.

Methods: In this multicenter, open-label, single-arm study, patients with BRAFV600E-mutated mCRC received oral encorafenib 300 mg once daily and binimetinib 45 mg twice daily in 28-day cycles, plus intravenous cetuximab 400 mg/m2 once on day 1 of cycle 1, then 250 mg/m2 once weekly for the first seven cycles, and 500 mg/m2 once on Days 1 and 15 from cycle 8 onward. The primary end point was locally assessed confirmed objective response rate (cORR), and secondary end points included centrally assessed cORR, progression-free survival, overall survival (OS), quality of life, and safety and tolerability.

Results: Among 95 patients, the locally assessed cORR was 47.4% (95% CI, 37.0 to 57.9) with all partial responses. Since the lower limit of the 95% CI exceeded 30%, the primary end point was met. With a median follow-up duration of 20.1 months, the median progression-free survival on the basis of local assessments was 5.8 months and the median OS was 18.3 months. Treatment was well tolerated, with no unexpected toxicities. Using Patient Global Impression of Changes, substantial improvement in symptoms was consistently reported in ≥ 30% of patients from cycle 3 to cycle 10.

Conclusion: The ANCHOR CRC study showed that the scientifically driven combination of encorafenib + binimetinib + cetuximab was active in the first-line setting of BRAFV600E-mutated mCRC with a manageable safety profile. Further first-line evaluation is ongoing (ClinicalTrails.gov identifier: NCT04607421).

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Josep Tabernero

Stock and Other Ownership Interests: Oniria Therapeutics

Consulting or Advisory Role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, Seattle Genetics, Array BioPharma, AstraZeneca, Genentech, Menarini, Servier, HalioDx, F. Hoffmann LaRoche, Mirati Therapeutics, Pierre Fabre, Tessa Therapeutics, TheraMyc, Daiichi Sankyo, Samsung Bioepis, IQvia, Ikena Oncology, Merus, NeoPhore, Orion Biotechnology, Hutchison MediPharma, Scandion Oncology, Ona Therapeutics, Sotio, Inspirna, Scorpion Therapeutics

Other Relationship: Medscape, MJH Life Sciences, PeerView, Physicians' Education Resource, iMedX/HMP

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Flow diagram (data cutoff date: June 29, 2020). PD, progressive disease.
FIG 2.
FIG 2.
Kaplan-Meier plots of (A) PFS and (B) OS in the full analysis set (n = 95). FAS, full analysis set; OS, overall survival; PFS, progression-free survival.
FIG 3.
FIG 3.
Mean ± SD change from baseline in (A) EQ-5D-5L VAS scores and (B) European Organization for Research and Treatment of Cancer QLQ-C30 global health status scores in the full analysis set (n = 95). C, cycle; D, day; EQ-5D-5L, 5-Level EuroQol 5-Dimension; FAS, full analysis set; QLQ-C30, Quality of Life Questionnaire Core 30; SD, standard deviation; SFU, standard follow-up; VAS, visual analog scale.
See this image and copyright information in PMC

References

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