560MO - Maintenance with 5FU/LV-Aflibercept after induction with FOLFIRI-Aflibercept vs FOLFIRI-Aflibercept until progression in older patients (pts) in 2nd line metastatic colorectal cancer (mCRC): The randomized AFEMA trial

Background

FOLFIRI-Aflibercept (A) is one of the 2nd-line standard treatments for mCRC. We evaluated the efficacy and safety of induction with FOLFIRI-A (6 cycles) followed by maintenance with 5FU/LV-A or FOLFIRI-A until progression in older pts with mCRC.

Methods

This was a multicenter, randomized, open-label, non-inferiority phase II trial. Pts aged ≥70 years who failed a prior oxaliplatin-based regimen, were randomly assigned (1:1) to induction with 6 cycles FOLFIRI-A followed by maintenance with 5FU/LV-A until progression (arm A, experimental) or FOLFIRI-A until progression (arm B, control). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), and safety. To claim non inferiority with 95% CI, the upper limit of the boundary could not exceed HR=1.5, with one-sided α=0.075 and 80% power.

Results

Between November 2017 and February 2022, 170 pts were randomized to arm A (n=85) or arm B (n=85). Both arms were comparable at baseline (median age 74 years). Over a median follow-up time of 12.2 months (m) in arm A vs 10.9 m in arm B, most pts had died (arm A 83.5%, arm B 88.2%) mainly from disease progression. Arm A was non inferior to arm B in terms of PFS (HR=0.781 [95% CI 0.566-1.076]). There were also no significant differences in OS and ORR between arms (Table). Grade ≥3 adverse events related to treatment occurred in 58.8% of pts in arm A vs 62.4% in arm B (p=0.754). Severe asthenia was significantly higher in arm B during the maintenance phase (4.5% vs 21.6%, p=0.038).

Conclusions

Primary endpoint was met: induction with 6 cycles FOLIRI-A followed by maintenance with 5FU/LV-A was non-inferior to FOLFIRI-A until progression, in terms of PFS. OS and ORR did not either differ between arms. In older pts, severe asthenia was significantly reduced with 5FU/LV-A maintenance.

Table: 560MO

^aLog-rank ^bFisher test

Clinical trial identification

NCT03279289.

Editorial acknowledgement

Medical writing assistance was provided by Carla Martín Cortázar from Evidenze Health España S.L. during the preparation of this abstract.

Legal entity responsible for the study

Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD).

Funding

Sanofi.

Disclosure

P. García Alfonso: Financial Interests, Personal, Advisory Board: Amgen. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: Organon, Novartis; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Travel, accommodations, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. J. Soto Alsar: Financial Interests, Institutional, Invited Speaker: Merck, Ipsen, Pfizer, Leo Pharma. A. Fernandez Montes: Financial Interests, Personal, Invited Speaker: Lilly, Pierre Fabre, Amgen, Servier, Eisai, AstraZeneca, MSD. A. Yubero Esteban: Financial Interests, Personal, Advisory Board: Clovis Oncology, AstraZeneca, GSK, Pharmamar; Financial Interests, Institutional, Local PI: WntResearch AB. I. Macias Declara: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD. C. Lopez Lopez: Financial Interests, Personal, Invited Speaker: Ipsen, Roche, Eisai, Novartis, Pfizer, AAA, Bayer, Lilly, Amgen, Merck, AstraZeneca, Servier; Financial Interests, Personal, Advisory Board: Ipsen, Roche, Eisai, Pfizer, Bayer, Lilly, Amgen, Merck, AstraZeneca, Servier; Financial Interests, Personal, Coordinating PI: Ipsen, Eisai; Financial Interests, Personal, Local PI: Ipsen, Roche; Financial Interests, Personal, Funding: Roche, Pfizer, Novartis, Bayer, Lilly, Eisai; Financial Interests, Personal, Steering Committee Member: Ipsen; Financial Interests, Personal and Institutional, Research Grant: Amgen, AstraZeneca, Servier. M. Guix Arnau: Financial Interests, Other: Bristol Myers Squibb, MSD, Merck; Financial Interests, Financially compensated role: Bristol Myers Squibb, MSD, Merck, Amgen. J. Sastre Varela: Financial Interests, Other: Merck, Roche, Lilly, Pfizer, Servier, MSD. All other authors have declared no conflicts of interest.