Abstract 2645
Background
FOLFIRI (5FU/leucovorin/irinotecan) + aflibercept significantly improves median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients (pts) with previously treated metastatic colorectal cancer (mCRC). The aim of this study was to investigate efficacy and tolerability of adding aflibercept to FOLFIRI in the first line setting.
Methods
Pts with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single arm, multicenter trial. The primary endpoint was the 6-months PFS rate. Secondary endpoints were overall PFS, OS and tolerability. A two- steps Simon design was used with H0: 55% and H1= 75%, respectively (one-sided α = 5%, 1-β=90%). Data were analyzed in intention to treat population. The study was stopped at the first stage.
Results
41 patients were included and 40 analyzed (1 consent withdrawal) in 9 French centers between 10/2014 and 02/2017. Median age was 65 y (46-81), 42% were men, 53% had two or more metastatic sites. Eighteen patients (54.5%, IC [38.940; 69.509]) were alive and non-progressive at 6 months. Treatment with FOLFIRI plus aflibercept was therefore considered ineffective, inclusions were stopped. Median follow-up was 20.5 months (95% CI (15,11 ; 27,86)). ORR was 54% and disease control rate was 80%. Median duration of treatment was 5.2 months, median PFS and OS were 8,3 and 21.9 months respectively. Grade 3-4 adverse events were mainly gastrointestinal (18 pts, 45% : mucositis (15%), diarrhea (12,5%), abdominal pain (10%)) and vascular (13 pts, 32,5% : hypertension (17,5%) and venous thromboembolism (15%)). Severe hematological toxicities occurred in 7,5% of pts. 87.5% of patients had at least one dose modification during treatment. 37 pts received a second line therapy.
Conclusions
First line FOLFIRI+ aflibercept for mCRC pts is feasible but with significant toxicities leading to dose reduction in the majority of patients. Median PFS and OS were close to those reported with classical doublet and targeted agents in this setting.
Clinical trial identification
EudraCT: 2013-004081-33.
Legal entity responsible for the study
Fédération Francophone de Cancérologie Digestive.
Funding
Sanofi.
Editorial Acknowledgement
Disclosure
S. Pernot: Honoraria: Amgen, Sanofi; Travel, accomodations, expenses: Amgen, Merck, Servier, Bayer T. Aparicio: Conference: Pfizer, Roche, Sanofi, Léo Pharma, Amgen, BMS, Servier, Shire, Ipsen; Board: Pierre Fabre Ipsen, HalioDX, BMS; Travels: Ipsen, Novartis, Roche, Hospira; Research: Novartis. L. Dahan: Honoraria: Sanofi, Amgen. T. Lecomte: Consultant, expert: Sanofi; Courses, trainings: Lilly, Merck, Amgen; Invitations to national or international congresses: Amgen C. Lepage: Clinical research: Ipsen, Novartis Oncology; Courses: Advanced Accelerator Applications; Invitations to national or international congresses: Amgen, Ipsen, Novartis Oncology, Bayer. J. Taieb: Consultancy: Roche, Merck KGaA, Amgen, Celgene, Lilly, Baxalta, Servier, Sirtex Medical; Speaker's bureau: Servier, Amgen, Baxalta, Roche/Genentech, Sanofi, Merck, Lilly. All other authors have declared no conflicts of interest.
Resources from the same session
1131 - Role of SPECT-CT somatostatin-receptor scintigraphy in the management of Medullary Thyroid Cancer (MTC)
Presenter: Sonya Sergieva
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5473 - A noninferiority trial of cabozantinib (C) comparing 60 mg vs 140 mg orally per day to evaluate the efficacy and safety in patients (pts) with progressive, metastatic medullary thyroid cancer (MTC)
Presenter: Jolanta Krajewska
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3367 - The role of SWI/SNF chromatin remodelling complex ATPase subunit – BRM in TNBC
Presenter: Iga Jancewicz
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2026 - Fluoropyrimidine and Inflammatory Genes Promoter Methylation in Egyptian CRC patients
Presenter: Mariam Fouad
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4125 - Realworld prospective data of small biopsy samples for tumor PD-L1 expression in non-small-cell lung cancer
Presenter: Kei Morikawa
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2367 - ATM as a DNA Damage Response Protein in Uveal Melanoma: Association with Clinicopathological Factors and Prognostic Outcome
Presenter: Jayanti Jha
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1305 - BRCA mutation and castration-resistant prostate cancer
Presenter: Liudmila Spirina
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3818 - Prevalence of KRAS mutation subtypes and MSI status in Pancreatic Cancer.
Presenter: Patan Gultawatvichai
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5976 - Molecular signature in malignant pleural mesothelioma (MPM): Preliminary data of Italian RAMES Study
Presenter: Francesca Zanelli
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4763 - N-Myc and STAT interactor (NMI) as a key determinant of chemosensitivity in breast cancer: proteomic-based computing network mapping and in vivo verification with a mouse model
Presenter: Hyebin Lee
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract