4287 - Safety and effectiveness of aflibercept + FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC): OZONE secondary analyses

Background

For patients with mCRC that have failed a first-line oxaliplatin-based regimen, the preferred treatment option is an irinotecan-based regimen. In these secondary analyses of the OZONE study, aflibercept + FOLFIRI safety and efficacy was evaluated for sub-populations of patients with mCRC.

Methods

OZONE is a prospective, multicentre, observational, non-comparative study evaluating patients receiving aflibercept + FOLFIRI in the clinical setting, for 24 months from aflibercept initiation or until death. Patients were grouped according to: age (≥ 65 years vs < 65 years); renal (CrCl ≤ 80 mL/min) or hepatic (bilirubin > UNL or AST/ALT > 1.5 UNL) impairment; number and type of prior anti-cancer therapy.

Results

From the overall population (N = 766), there were 370 patients aged ≥ 65 years. All grade asthenia (43.5% vs 35.9%) and decreased appetite (25.4% vs 20.2%) occurred more frequently (≥ 5%) in patients aged ≥ 65 vs < 65 years. There were 256 patients with CrCl ≤ 80 mL/min, of which 43 had CrCl < 50 mL/min. Renal function did not influence treatment-emergent adverse events (TEAEs). Grade ≥ 3 TEAEs were reported in 76.7%, 67.1% and 67.9% of patients with CrCl < 50 mL/min, CrCl 50–80 mL/min, and CrCl > 80 mL/min, respectively. There were 129 patients with impaired liver function. All grade constipation and haemorrhage were more frequent in patients with impaired liver function vs those without (23.3% vs 14.2% and 37.2% vs 30.1%, respectively). There were 449 patients previously treated with bevacizumab. Only fatigue occurred more frequently in patients with prior bevacizumab vs those without (23.8% vs 17.0%). Efficacy multivariate analyses showed that treatment with aflibercept + FOLFIRI favoured patients without vs with hepatic impairment (median overall survival [OS] 13.7 vs 8.7 months; p < 0.001) and without vs with prior use of bevacizumab (median OS 16.6 vs 10.6 months; p < 0.001).

Conclusions

Subgroup analyses of the OZONE study did not reveal major differences in the safety profile according to age, renal or hepatic status, or prior bevacizumab status. These results suggest that aflibercept may be a treatment option for these subgroups of patients. Funding: Sanofi.

Clinical trial identification

ENCEPP/SDPP/4836.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Sanofi.

Disclosure

I. Chau: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Eli-Lilly; Advisory / Consultancy: Bristol Meyers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (self): Merck-Serono; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Oncologie International; Advisory / Consultancy: Pierre Fabre; Research grant / Funding (self): Janssen-Cilag; Research grant / Funding (self): Sanofi Oncology. P. García-Alfonso: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol Meyers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Sanofi Oncology; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Servier. Z. Linke: Advisory / Consultancy, Advisory Board- Oncologic days in Bratislava, Slovakia, 2016, 2017, 2018 and Prague in 2018.: Sanofi; Speaker Bureau / Expert testimony, Lecture- Prague Onco 2019: Merck; Non-remunerated activity/ies, ESMO 2017: Roche. A. Ruiz-Casado: Research grant / Funding (self): Sanofi; Research grant / Funding (self): Servier; Research grant / Funding (self): Amgen; Research grant / Funding (self): Merck; Research grant / Funding (self): Lilly; Research grant / Funding (self): Roche; Research grant / Funding (self): Medtronic; Research grant / Funding (self): BTG. E. Polo Marques: Research grant / Funding (self): Roche; Research grant / Funding (self): Amgen; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Merck. T. Cartwright: Research grant / Funding (self): Amgen; Research grant / Funding (self): Taiho. All other authors have declared no conflicts of interest.