Dataset Information

Real-World Evaluation of Quality of Life, Effectiveness, and Safety of Aflibercept Plus FOLFIRI in Patients with Metastatic Colorectal Cancer: The Prospective QoLiTrap Study.

ABSTRACT: Aflibercept plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer after the failure of oxaliplatin-containing therapy. QoLiTrap prospectively evaluated the quality of life (QoL) and effectiveness of this regimen in daily clinical practice, according to RAS status, sex, and prior targeted therapy, especially epidermal growth factor receptor inhibitors (EGFR-I). The primary endpoint was the percentage of patients whose EORTC QLQ-C30 global health status (GHS) improved or reduced by <5% from baseline during the first 12 weeks of therapy. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. One thousand two hundred and seventy-seven patients were treated with aflibercept plus FOLFIRI and 872 were evaluable for QoL. GHS improved or decreased by <5% in 40.3% of cases. The ORR was 20.8%, the median PFS was 7.8 months (95% confidence interval (CI), 7.3-8.3), and the median OS was 14.4 months (95% CI, 13.1-18.1). After prior EGFR-I, the ORR was 23.7%, median PFS was 9.4 months (95% CI, 6.5-12.9), and median OS was 17.4 months (95% CI, 10.5-33.7). The safety profile was consistent with previously reported data. Aflibercept plus FOLFIRI given in daily practice maintained QoL in mCRC patients, was associated with a high objective tumor response, and retained its activity regardless of sex, RAS status, and prior EGFR-I therapy.

SUBMITTER: Hofheinz RD

PROVIDER: S-EPMC9324206 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Real-World Evaluation of Quality of Life, Effectiveness, and Safety of Aflibercept Plus FOLFIRI in Patients with Metastatic Colorectal Cancer: The Prospective QoLiTrap Study.

Hofheinz Ralf-Dieter RD Anchisi Sandro S Grünberger Birgit B Derigs Hans G HG Zahn Mark-Oliver MO Geffriaud-Ricouard Christine C Gueldner Max M Windemuth-Kieselbach Christine C Pederiva Stefanie S Bohanes Pierre P Scholten Felicitas F Piringer Gudrun G Thaler Josef J von Moos Roger R

Cancers 20220720 14

Aflibercept plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer after the failure of oxaliplatin-containing therapy. QoLiTrap prospectively evaluated the quality of life (QoL) and effectiveness of this regimen in daily clinical practice, according to RAS status, sex, and prior targeted therapy, especially epidermal growth factor receptor inhibitors (EGFR-I). The primary endpoint was the percentage of patients whose EORTC QLQ-C30 global health status (GHS) im ...[more]

PMID: 35884583

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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.

Project description:BackgroundNon-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients.ObjectiveWe present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses.MethodsThis was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex® multiplex assay U-kit.ResultsBetween January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month-not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor (p = 0.7), while it tended to be shorter in those with high levels of osteopontin (p = 0.05), angiopoietin-2 (p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 (p = 0.1).ConclusionsThis study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment.Clinical trial registrationjRCTs041190100.

Project description:BackgroundFOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC.MethodsEFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer.DiscussionThis is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered.Trial registrationJapan Registry of Clinical Trials jRCTs071190003 . Registered April 18, 2019.

Dataset Information

Real-World Evaluation of Quality of Life, Effectiveness, and Safety of Aflibercept Plus FOLFIRI in Patients with Metastatic Colorectal Cancer: The Prospective QoLiTrap Study.

Publications

Real-World Evaluation of Quality of Life, Effectiveness, and Safety of Aflibercept Plus FOLFIRI in Patients with Metastatic Colorectal Cancer: The Prospective QoLiTrap Study.

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