626P - Mucinous differentiation (MD) as predictor of response in BRAF-V600E mutated metastatic colorectal cancer (mCRC) treated with BRAF inhibitors (BRAFi) combinations

Background

In BRAF-V600E mutated metastatic colorectal cancer (mCRC), 40% of tumors present with MD. This feature has been associated with poor prognostic and resistance to chemotherapy. However, the clinical impact of the presence of MD in patients treated with BRAFi remains unclear. Aim: The aim of this study is to evaluate the clinical impact of MD in a cohort of patients with BRAF-V600E mutated mCRC treated with BRAFi.

Methods

Patients with BRAF-V600E mCRC treated at Vall d’Hebron Hospital from 2019 to 2021 were included. MD was determined baseline based on the percentage of neoplasic mucinous component (FFPE). Data were collected prospectively. Survival analysis were calculated using K-M curves.

Results

A total of 54 patients were included, with a median age of 62 years, and 61% were females. Of these patients, 65% had right-sided tumors, 11% had MSI. 68% of patients received BRAFi-antiEGFR, while 32% received BRAFi-antiEGFR-MEKi. Initially, a dichotomic MD was established based on the presence or absence of tumoral mucin, with 36 and 17 patients, respectively. ORR was 41% and 25% for mucinous and non-mucinous tumors, respectively. PFS was 8.43 months (HR 0.49, 95%CI 4.83-11.1, p 0.02) for mucinous tumors, compared to 3.84 months for non-mucinous tumors. Mucinous tumors tended to have better overall survival (OS) (14 vs 10.2 months, HR 1.3, 95%CI 0.4-1.4, p 0.4). Then, we evaluated whether the percentage of tumor mucin impacted outcomes. Three groups were established based on an arbitrary cut-off of 20%: high-mucin -HM- (>20% of mucin, n:17), low-mucin -LM- (<20% of mucin, n:11), and non-mucinous -NM- (n:17). ORR was 68%, 33%, and 25%, respectively. Patients with high-mucin had better PFS compared to non-mucinous tumors, 9.4 months vs 3.84 months (HR 0.87, 95%CI 0.17-0.9, p 0.02). Patients with low-mucin tended to have better PFS than non-mucinous tumors (5.62 months, HR 1.2, 95%CI 4.60-12.9, p 0.08). Tumors with MD tended to have better OS in both groups (15 months in the HM group, 16.6 months in the LM group vs 10.2 months in the NM group).

Conclusions

Tumor mucin may be a potential predictive biomarker in BRAF-V600E mutated mCRC patients treated with BRAF inhibitors. Further validation is required.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F.J. Ros Montana: Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: Amgen. H.G. Palmer: Financial Interests, Personal, Ownership Interest: Oniria Therap. N. Saoudi Gonzalez: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; Financial Interests, Personal, Other: Merck, Amgen. I. Baraibar Argota: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; Financial Interests, Personal, Other: Servier. M. Rodriguez Castells: Financial Interests, Personal, Speaker, Consultant, Advisor: Rovi; Financial Interests, Personal, Other: Merck, Bristol Myers Squibb, Merck. F. Salvà Ballabrera: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Sanofi, Merck; Financial Interests, Personal, Other: Amgen. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex / HMP; Financial Interests, Personal, Invited Speaker, Educacional collaboration: MJH Life Sciences; Financial Interests, Personal, Advisory Board: Cardiff Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeuics; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, , Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, , Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Celgene International SARL, Bristol Myers Squibb International Corporation, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc.; Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, , Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc.; Non-Financial Interests: HalioDX SAS. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: Organon, Novartis; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Travel, accommodations, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. All other authors have declared no conflicts of interest.