Abstract 445P
Background
BRAF-V600E mt mCRC is an aggressive disease with poor OS under standard chemotherapy. Treatment with doublet and triplet targeted combinations, such as BRAF inhibitor+ antiEGFR+/- MEK inhibitor, has been shown to improve outcomes. Prognostic factors in this population have been already described. However, prognostic factors in a homogenous population under BRAF inhibitor-based treatment have not been previously described.
Methods
A prospective international cohort of patients who received doublet or triplet anti-BRAF combinations in clinical trials or as compassionate use. Univariate Cox models for OS were constructed and the strongest predictors in stepwise variable selection were used to develop a prognostic score. The final multivariate model with selected predictors was stratified by prior lines.
Results
In total, 77 pts were enrolled. Median age 60.3 y (33-83), 55.8% female, 66.2% right-sided tumors, 60% received 2 or more prior chemotherapy lines. Three patients (4%) achieved CR and 25.7% had PR. 50 patients received doublet, and 27 patients received triplet. Overall, median PFS was 4.9m (CI95% 4.3-6.5) and median OS was 8.2 months (m) (CI95% 7.3-11.6). ECOG performance status, stage, number of tumour sites, presence of liver metastases, WBC, neutrophils, albumin CEA and NLR levels were associated with OS (p-value <0.05 in the univariate analysis). In the multivariate analysis, the most parsimonious model included four factors: ECOG, presence of liver metastases, CEA, and NLR levels. We stratified patients into three risk prognostic groups based on their number of presenting risk factors: 0 low risk (n = 17); 1-2, intermediate risk (n = 39); 3 or 4, high risk (n = 21). These three prognostic groups showed differentiated OS outcomes, with a median OS of 23.2m, 9.8m [HR=6.6, p<0.001], and 5m [HR=39.9, p<0.001] respectively.
Conclusions
Patients characteristics such as ECOG and surrogates of tumor burden like CEA levels or the number of metastatic sites remain important OS determinants for this particular population. Our study suggests that these prognostic factors could help in clinical practice and may be considered as stratification factors in future clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I. Baraibar: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Sanofi. D. Ciardiello: Financial Interests, Personal, Other, travel grant: Luigi Van Vitelli University. R.D.A. Toledo: Financial Interests, Personal, Research Grant: Novartis, AstraZeneca and Beigene. E. Martinelli: Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Bayer, Merck-Serono, Roche, Sanofi, Servier, Pierre-Fabre. F. Ciardiello: Financial Interests, Personal, Invited Speaker, Advisor and speaker: Roche, Amgen, Merck-Serono, Pfizer, Sanofi, Bayer, BMS, Cellgene, Lilly; Financial Interests, Institutional, Research Grant: Bayer, Roche, Merck-Serono, Amgen, AstraZeneca, Takeda. A. Vivancos: Financial Interests, Personal, Advisory Board, advisory role, travel grants, research grants: offman La - Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: Array Biopharma, MSD, AbbVie, Amgen, GlaxoSmithKline, AstraZeneca, Merck Sharp & Dohme Corp., Bristol Myers Squibb, Novartis, Boehringer Ingelheim, Hoffman La-Roche, Medimmune, Pierre-Fabre, Sanofi Aventis.. R. Dienstmann: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck and Pierre Fabre. J. Tabernero: Financial Interests, Personal, Advisory Board: array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Diichi Sankyo, Roche, Genentech, HalioDX, Hutchinson MediPharma, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore; Financial Interests, Institutional, Sponsor/Funding, Financial support for clinical trials or contracted research: Amgen Inc, Array Biopharma, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Celgene, Debiopharm, Roche, Genentech Inc, Halio Dx SAS, Hutchinson MediPharma, Janssen-Cilag, MedImmune, Menarini, Merch Health KGAA, Merck Shapr and Dohme, MErus NV, Mirati, No; Non-Financial Interests, Personal and Institutional, Other: Role of Principal Investigator, Coordinating Investigator or Steering Committee member: Array Biopharma, AstraZeneca Pharmaceutical, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Debiopharm, F.Hoffmann-La Roche, Genentech, HalioDX, Hutchin. M.E. Elez Fernandez: Financial Interests, Personal, Invited Speaker: Hoffman La - Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer, Hoffman La - Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: Array Biopharma, MSD, AbbVie, Amgen, GlaxoSmithKline, Astrazeneca, Merck Sharp & Dohme Corp., Bristol Myers Squibb, Novartis, Boehringer Ingelheim, Hoffman La-Roche, Medimmune, Pierre-Fabre, Sanofi Aventis. All other authors have declared no conflicts of interest.