The Ph 3 VELOUR study demonstrated that addition of aflibercept (ziv-aflibercept [USA]) to fixed-dose FOLFIRI improved survival outcomes & response rates in mCRC pts treated with prior oxaliplatin-based chemotherapy. The global ASQoP study (NCT01571284) is a single-arm, open-label trial in a population similar to VELOUR, evaluating QoL and safety in a closer to real-life setting. Here, we report safety data from the 5th interim analysis of ASQoP.
ASQoP enrolled mCRC pts (ECOG PS 0–1) with prior oxaliplatin-based therapy, regardless of prior bevacizumab (Bev) therapy. Pts received 4 mg/kg aflibercept & FOLFIRI on d1 of a 2-wk cycle, until disease progression (PD), unacceptable toxicity, death or investigator/pt decision. Initial FOLFIRI dose & subsequent modifications were at physician's discretion. Adverse events (AEs) were evaluated using CTCv4.03.
At data cut-off (7 Mar 2016), the safety population (≥1 full treatment cycle) comprised 779 pts: male 59.7%; ECOG PS = 0 62.0% (VELOUR 57.0%); median age 61.0 y (VELOUR 61.0 y); age ≥65 y 39.0%; median time from diagnosis 13.4 mo; prior Bev 46.2%; prior thrombovascular events/presence of CV risk factors 54.4%. In total, 774 pts discontinued treatment, mostly due to PD (52.3%) or AEs (26.7%). Among pts who discontinued treatment, the median no. of cycles was 7 (VELOUR 9 cycles); median duration of exposure was 16.6 wks (VELOUR 21.4 wks). A summary of the AEs in ASQoP and VELOUR are in the table. ASQoP is an ongoing study; these results are not final.
Aflibercept-related toxicity was similar in ASQoP and VELOUR. The frequency of some AEs appears lower in ASQoP, which may reflect more flexible FOLFIRI dosing, or more routine in AE management. Overall, the safety profile in ASQoP was consistent with the known safety profile of aflibercept/FOLFIRI, with no new safety signals identified.
|ASQoP – 5th interim analysis Aflibercept + FOLFIRI (n = 779)||VELOUR flibercept + FOLFIRI (n = 611)|
|Patients (%)||All grades||Grade 3–4||Grade 4||All grades||Grade 3–4||Grade 4|
|Selected TEAEs of any grade in ≥20% of patients|
|Asthenic conditions (HLT)||57.8||13.6||0||60.4||16.9||0.8|
|Hypertension (grouped term)||48.4||24.1||0||41.4||19.3||0.2|
|Stomatitis and ulcerations (HLT)||43.5||10.7||0.1||54.8||13.7||0.2|
|Infections and infestations (SOC)||31.3||11.7||2.1||46.2||12.3||1.3|
|Venous thromboembolic events (grouped term)||6.2||4.1||0.9||9.3||7.9||4.7|
|Arterial thromboembolic events (grouped term)||2.3||0.8||0.3||2.6||1.8||1.0|
|Gastrointestinal perforation (grouped term)||1.4||1.4||0.6||0.5||0.5||0.3|
|Fistula (gastrointestinal origin) (grouped term)||1.8||0.8||0||1.1||0.3||0|
*n = 744; **n = 603 HLT, high-level term; PT, preferred term; SOC, system organ class; TEAE, treatment-emergent adverse event
Clinical trial identification
Legal entity responsible for the study
P. Kavan: Educational grant from Sanofi in 2013 and 2014, not directly related to presented topic. E. Maiello: Membership on Advisory Board (last two years) for Celgene, Roche, Sanofi, Lilly, Amgen, Merck, Bayer. P. Garcia-Alfonso: Advisory Boards: Roche, Merck, Amgen, Lilly, Sanofi, Bayer. I. Chau: Advisory Boards for Sanofi Oncology, Eli-Lilly, Bristol Meyers Squibb, MSD, Merck Serono, Gilead. Science research funding: Janssen-Cilag, Sanofi Oncology, Roche, Merck-Serono, Novartis. Honorarium: Taiho, Pfizer, Amgen, Eli-Lilly, Bayer. M. Peeters: Advisory Board and speaker: Sanofi. P. Picard: Employee of Sanofi (contracted by AIXIAL). R. Bordonaro: Honoraria for participation in advisory boards and/or as a consultant and/or participation as a speaker at meetings for Novartis, Hoffman-La Roche, Merck, Eli Lilly, Sanofi, Boheringer-Ingleheim. All other authors have declared no conflicts of interest.