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A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI.

ABSTRACT: The VELOUR study demonstrated a survival benefit for FOLFIRI?+?aflibercept versus FOLFIRI?+?placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR had recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers)--previously identified as having poorer survival outcomes.To determine which patients received the greatest benefit from FOLFIRI-aflibercept, a post hoc multivariate analysis of the VELOUR ITT population was conducted. Prognostic factors identified were applied to the ITT population, excluding adjuvant fast relapsers, to derive OS prognostic profiles.The better efficacy subgroup was identified as patients within VELOUR exclusive of adjuvant fast relapsers and had performance status (PS) 0 with any number of metastatic site or PS 1 with <2 metastatic site. A significant improvement in efficacy outcome was observed with aflibercept in the better efficacy subgroup. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo:16.2 and 13.1 months (adjusted Hazard Ratio [HR]?= 0.73; 95% confidence interval [CI]: 0.61-0.86); median progression free survival (PFS): 7.2 and 4.8 months (adjusted HR = 0.68; 95% CI: 0.57-0.80); and objective response rate (ORR): 24% versus 11% respectively. Poorer efficacy subgroup comprised of adjuvant fast relapsers or patients with PS2 or PS1 with ? 2 metastatic sites. In poorer efficacy subgroup, no benefit was seen with aflibercept. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo: 10.4 and 9.6 months (adjusted HR = 0.97; 95% CI: 0.78-1.21) respectively with no improvement in PFS or ORR.This analysis suggests that within VELOUR, patients in the better efficacy subgroup may derive enhanced benefit from treatment with FOLFIRI-aflibercept. These prognostic criteria may guide practitioners toward optimal use of targeted biologicals in appropriate second-line mCRC patients.

SUBMITTER: Chau I

PROVIDER: S-EPMC4149045 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI.

Chau Ian I Joulain Florence F Iqbal Sheikh Usman SU Bridgewater John J

BMC cancer 20140820

<h4>Background</h4>The VELOUR study demonstrated a survival benefit for FOLFIRI + aflibercept versus FOLFIRI + placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR ...[more]

PMID: 25142418

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Project description:Background: The prognosis of patients with metastatic colorectal cancer (mCRC) is poor, especially after failure of initial systemic therapy. The VELOUR study showed modestly prolonged overall survival (OS) with ziv-aflibercept plus 5-fluorouracil, leucovorin, and irinotecan (zFOLFIRI) vs. placebo+FOLFIRI after progression on 5-fluoruracil, leucovorin, and oxaliplatin (FOLFOX) ± bevacizumab. The utility of zFOLFIRI after bevacizumab+FOLFIRI is unknown and not recommended in NCCN guidelines. We explored whether zFOLFIRI may be active beyond progression on bevacizumab+FOLFIRI. Methods: We undertook a retrospective analysis of patients treated in routine clinical practice. A chart review was conducted for a cohort (N = 19) of advanced cancer patients (18 mCRC) who received zFOLFIRI from 2014 to 2018 at Fox Chase Cancer Center (FCCC). Analysis included time on zFOLFIRI, PFS, OS, CEA trends and adverse events. A second mCRC cohort (N = 26) from the Flatiron Health EHR-derived database treated with zFOLFIRI after prior bevacizumab+FOLFOX and bevacizumab+FOLFIRI was analyzed for time-on-treatment and overall survival. Results: Median age of mCRC cohort at zFOLFIRI treatment was 54 (FCCC; N = 18) and 62 (Flatiron Health-cohort; N = 26). Of 18 FCCC mCRC patients, 1 patient had prior bevacizumab+FOLFOX and ramucirumab+irinotecan prior to zFOLFIRI for 8.5 months. Of 17 FCCC mCRC patients with prior bevacizumab+FOLFIRI who received zFOLFIRI, 13 had mutant-KRAS, 3 WT-KRAS, and one BRAF-V600E. The patient with BRAF-V600E mutation achieved stable disease on zFOLFIRI after multiple BRAF-targeted therapies. One patient (WT-KRAS mCRC) remained on zFOLFIRI for 14 months. Of 14 patients with mutated-KRAS, 8 remained on zFOLFIRI for >5 months including 3 for >15 months. The rate-of-change in CEA measures on zFOLFIRI was significantly different (p = 0.004) between rapid progressors and those with PFS>4 months. For mCRC patients treated with zFOLFIRI in the 3rd line or greater (N = 18), median PFS was 7.1 months (214 days) and median OS was 13.8 months (416 days). Median time-on-treatment with zFOLFIRI in the Flatiron Health cohort was 4.4 months, median OS was 7.8 months, and longest time-on-treatment with zFOLFIRI was 266 days. Conclusions: In these small real-world cohorts, clinical meaningful stable disease and overall survival on zFOLFIRI beyond progression on bevacizumab+FOLFIRI was observed in patients with mCRC. Further exploration of this approach is warranted.

Dataset Information

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI.

Publications

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI.

Similar Datasets

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