Dataset Information

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

ABSTRACT:

Introduction

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.

Methods

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.

Results

In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS/BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p < 0.001; OS: p = 0.012) and molecular subgroup (PFS: p < 0.001; OS: p < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p < 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965).

Conclusions

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.

SUBMITTER: Kurreck A

PROVIDER: S-EPMC8895369 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Kurreck Annika A Heinemann Volker V Fischer von Weikersthal Ludwig L Decker Thomas T Kaiser Florian F Uhlig Jens J Schenk Michael M Freiberg-Richter Jens J Peuser Bettina B Denzlinger Claudio C Graeven Ullrich U Heinrich Kathrin K Held Swantje S Stahler Arndt A Alig Annabel Helga Sophie AHS Jelas Ivan I von Einem Jobst C JC Stintzing Sebastian S Giessen-Jung Clemens C Modest Dominik P DP

Frontiers in oncology 20220218

<h4>Introduction</h4>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.<h4>Methods</h4>DpR ( ...[more]

PMID: 35251955

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Project description:BackgroundIn metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer.MethodsPatients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n = 164) or placebo (n = 162) prior to FOLFOXIRI/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil/leucovorin/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety.ResultsThe study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P = .009) and median progression-free survival (10.3 vs 13.1 months; P < .001) were significantly lower with trilaciclib vs placebo.ConclusionsAdministering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.Trial registrationClinicalTrials.gov: NCT04607668.

Dataset Information

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

Introduction

Methods

Results

Conclusions

Publications

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

Similar Datasets

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