Dataset Information

Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study.

ABSTRACT: For patients with metastatic colorectal cancer (mCRC) that have failed a first-line oxaliplatin-based regimen, the preferred treatment option is an irinotecan-based regimen. This prospective, observational, noncomparative, post-authorization safety study (OZONE) evaluated the safety and effectiveness of aflibercept plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) in patients with mCRC treated in daily practice after failure of an oxaliplatin-based regimen. Patients were grouped by age, renal impairment, hepatic impairment, race, number, and type of prior anticancer therapy. Of 766 treated patients enrolled, 59.5% were male, 94.8% had an Eastern Cooperative Oncology Group performance status of 0-1, all received previous chemotherapy (97.8% including oxaliplatin), and 58.6% had prior exposure to bevacizumab. At least one grade ? 3 treatment-emergent adverse event (TEAE) was reported in 68.3% of patients. Neutropenia, hypertension, diarrhea, and asthenia were the most frequently occurring grade ? 3 TEAEs. Antivascular endothelial growth factor class events were infrequent. Subgroup analyses did not reveal major differences in the safety profile according to age, renal and hepatic status, race, or prior anticancer therapy. For the total population, median overall survival was 12.5 months, median progression-free survival was 6.1 months, and overall response rate was 16.3%. Aflibercept in combination with FOLFIRI is a safe and efficacious regimen administered in current clinical practice to patients with mCRC previously treated with oxaliplatin. The study results, conducted in real-world clinical practice with a less selected patient population, are aligned with the VELOUR (NCT00561470) trial and no new safety issues were identified.

SUBMITTER: Chau I

PROVIDER: S-EPMC7139359 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study.

Chau Ian I Fakih Marwan M García-Alfonso Pilar P Linke Zdenĕk Z Ruiz Casado Ana A Marques Eduardo Polo EP Picard Pascaline P Celanovic Marina M Cartwright Thomas T

Cancers 20200311 3

For patients with metastatic colorectal cancer (mCRC) that have failed a first-line oxaliplatin-based regimen, the preferred treatment option is an irinotecan-based regimen. This prospective, observational, noncomparative, post-authorization safety study (OZONE) evaluated the safety and effectiveness of aflibercept plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) in patients with mCRC treated in daily practice after failure of an oxaliplatin-based regimen. Patients were grouped by age, re ...[more]

PMID: 32168980

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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:IntroductionLiposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has shown clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on gemcitabine-based chemotherapy. However, its role in patients with mPAC previously treated with conventional irinotecan-containing chemotherapy has not been appropriately investigated.MethodsIn this retrospective analysis, patients with mPAC who received nal-IRI plus 5-FU/LV after conventional irinotecan-containing regimen between January 2017 and March 2020, were identified from two referral cancer centers in South Korea. The ratio of time to progression (TTP) with nal-IRI plus 5-FU/LV to TTP with conventional irinotecan (TTPr) was analyzed with respect to the duration and cumulative dose of conventional irinotecan treatment.ResultsIn total, 35 patients treated with nal-IRI plus 5-FU/LV after the irinotecan-containing regimen were analyzed. The median age was 58 years and 16 (46%) patients were male. The median duration of conventional irinotecan therapy was 4.6 months at a median cumulative dose of 1230 mg. The objective response rate of nal-IRI plus 5-FU/LV was 2.9%, and stable disease was achieved in 11 (31.4%) patients. During the median follow-up of 9.2 [95% confidence interval (CI): 7.8-10.5] months, the median progression-free survival (PFS) and overall survival (OS) were 2.0 (95% CI: 1.4-2.6) months and 4.4 (95% CI: 3.6-5.7) months, respectively. The 6-month PFS and OS rates were 16.3% and 37.5%, respectively. The median TTPr was 0.41 (range, 0.07-2.07), showing a negative correlation with the cumulative dose of prior irinotecan therapy (R = -0.37, p = 0.041). A tentative negative correlation between TTPr and duration of prior irinotecan therapy was observed (R = -0.35, p = 0.062). The most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%).ConclusionNal-IRI plus 5-FU/LV showed modest effectiveness and manageable toxicities for patients with mPAC previously treated with conventional irinotecan-containing chemotherapy. The cumulative dose of prior conventional irinotecan therapy may be inversely correlated with the effectiveness of nal-IRI plus 5-FU/LV.

Dataset Information

Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study.

Publications

Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study.

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