KEY TAKEAWAYS
- XELAVIRI trial (NCT01249638), phase 3, analyzed 370 mCRC patients treated with first-line bevacizumab-based sequential or combination chemotherapy.
- ETS, DpR, and time to DpR may serve as early efficacy parameters and predictors of long-term outcomes in mCRC.
- Initial irinotecan-based combination therapy with bevacizumab improves ETS and DpR in mCRC patients, particularly RAS/BRAF wild-type tumors.
- ETS is a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC.
- ETS correlates with improved survival irrespective of treatment arm and molecular subgroup.
Promising early efficacy parameters and predictors of long-term outcomes in metastatic colorectal cancer (mCRC) include early tumor shrinkage (ETS), depth of response (DpR), and time to DpR. In the phase 3 XELAVIRI trial, researchers compared the outcomes of mCRC patients treated with sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) bevacizumab-based chemotherapy. ETS (20% reduction in tumor diameter at first reassessment), DpR (change from baseline to most minor tumor diameter), and time to DpR (study randomization to DpR image) were analyzed. Researchers used ETS as a stratification parameter to compare PFS and OS across treatment groups, molecular subgroups, and gender. Of the 370 patients studied, the initial combination therapy group had a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and a significantly higher DpR (-40.0% vs. -24.7%; p< 0.001). In RAS/BRAF wild-type tumors, the enhancement was striking.
Regardless of treatment arm or molecular subgroup, ETS was associated with better survival (PFS: p< 0.001; OS: p = 0.012). When comparing ETS patients of both sexes, men fared better overall survival (PFS: p< 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965). Initial combination therapy based on irinotecan and bevacizumab improved ETS and DpR in patients with mCRC whose tumors exhibited a high sensitivity to irinotecan due to the presence of RAS/BRAF wild-type mutations. In mCRC, ETS is an appropriate prognostic marker for combinations based on fluoropyrimidines and bevacizumab. More men than women contributed to this finding, which could mean that ETS is less indicative of long-term outcomes in the elderly female population.
Source: https://pubmed.ncbi.nlm.nih.gov/35251955/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT01249638
Kurreck A, Heinemann V, Fischer von Weikersthal L, Decker T, Kaiser F, Uhlig J, Schenk M, Freiberg-Richter J, Peuser B, Denzlinger C, Graeven U, Heinrich K, Held S, Stahler A, Alig AHS, Jelas I, von Einem JC, Stintzing S, Giessen-Jung C, Modest DP. Response and Disease Dynamics in Untreated Metastatic Colorectal Cancer With Bevacizumab-Based Sequential vs. Combination Chemotherapy-Analysis of the Phase 3 XELAVIRI Trial. Front Oncol. 2022 Feb 18;12:751453. doi: 10.3389/fonc.2022.751453. PMID: 35251955; PMCID: PMC8895369.
