Response and Disease Dynamics in Untreated Metastatic Colorectal Cancer With Bevacizumab-Based Sequential vs. Combination Chemotherapy-Analysis of the Phase 3 XELAVIRI Trial.

Early tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial. DpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex. In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; Initial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.

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Copyright © 2022 Kurreck, Heinemann, Fischer von Weikersthal, Decker, Kaiser, Uhlig, Schenk, Freiberg-Richter, Peuser, Denzlinger, Graeven, Heinrich, Held, Stahler, Alig, Jelas, von Einem, Stintzing, Giessen-Jung and Modest.

Déclaration de conflit d'intérêts

AK: Honoraria: Taiho Pharmaceutical, Servier; Travel, Accommodations, Expenses: Roche, Medac. VH: Honoraria: Roche, Celgene, Amgen, Sanofi, Merck, Sirtex Medical, Baxalta, Eli Lilly, Boehringer Ingelheim, Taiho Pharmaceutical, Servier; Consulting or Advisory Role: Merck, Amgen, Roche, Sanofi, Boehringer Ingelheim, Celgene, Sirtex Medical, Baxalta, Servier, Halozyme, MSD, Bristol-Myers Squibb; Research Funding: Merck (Inst), Amgen (Inst), Roche (Inst), Celgene (Inst), Boehringer Ingelheim (Inst), Sirtex Medical (Inst), Shire (Inst); Travel, Accommodations, Expenses: Merck, Roche, Sirtex Medical, Amgen, Servier, Shire, MSD, Bristol-Myers Squibb. LF: Honoraria: Novartis, Roche, Sanofi; Travel, Accommodations, Expenses: Amgen. TD: Consulting or Advisory Role: Novartis. CD: Honoraria: Janssen, Novartis, Celgene, Incyte; Consulting or Advisory Role: Abbvie, Bayer; Travel, Accommodations, Expenses: Merck. UG: Honoraria: Servier, Boehringer Ingelheim, Sirtex Medical, Daiichi Sankyo; Consulting or Advisory Role: Novartis, Merck, Amgen, Hexal, Bristol-Myers Squibb;Travel, Accommodations, Expenses: Merck, Amgen. AS: Honoraria: Roche, Servier/Taiho; Travel, Accommodations, Expenses: Roche, Merck KGaA, MSD Sharp & Dohme, Pfizer, Amgen. KH: Honoraria: Roche; Travel, Accommodations, Expenses: AMGEN, Celgene, Lilly. SH: Employed: ClinAssess GmbH. AA: Consulting or Advisory Role: Roche; Travel, Accommodations, Expenses: Pfizer, Roche, Eli Lilly, Novartis, PharmaMar. JE: Honoraria: Merck, Roche, Amgen, Sanofi, Pierre-Fabre, Servier, Taiho, BMS, Eisai, Novartis; Consulting or Advisory Role: Amgen, Pierre-Fabre, BMS, Servier; Travel, Accommodations, Expenses: AstraZeneca, Apceth. SS: Honoraria: AMGEN, Bayer, BMS, ESAI, Lilly, Merck KGaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, Takeda; Consulting or Advisory Role: AMGEN, Bayer, BMS, ESAI, Lilly, Merck KGaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, Takeda; Travel, Accommodations, Expenses: Merck, Roche, Sanofi, Bayer, Sirtex Medical, Amgen, Eli Lilly, Takeda, Pierre Fabre. CG-J: Travel, Accommodations, Expenses: Roche. DPM: Honoraria: Merck Serono, Amgen, Roche, Servier, Bristol-Myers Squibb, Pfizer, Sirtex Medical; Consulting or Advisory Role: Merck Serono, Amgen, Bayer; Research Funding: Merck Serono (Inst), Roche (Inst), Amgen (Inst); Travel, Accommodations, Expenses: Amgen, Merck Serono, Bayer, Servier, Bristol-Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.