Aflibercept and 5-FU vs. FOLFOX as 1st line treatment for older adults or frail elderly patients with metastatic colorectal cancer - The randomized phase 2 AIO / IKF ELDERLY trial (AIO-KRK-0117 / IKF 629)

Clinical Snapshot

Key Findings

• P Value: Not reported for primary comparison

• Effect Size: 22 percentage point difference in PFS@6 favoring mFOLFOX7

• Primary Outcome: 6-month PFS rate: 68% (95%CI 56-80%) mFOLFOX7 vs 46% (95%CI 32-59%) aflibercept/5-FU

• Nnt Or Sensitivity: Number needed to treat approximately 5 for one additional patient to achieve 6-month PFS with mFOLFOX7

• Confidence Interval: 95%CI provided for primary endpoint only

Clinical Application

Both regimens feasible in elderly/frail population, though mFOLFOX7 showed superior efficacy with manageable toxicity profile Both regimens PBS-listed; findings support current COSA guidelines for dose-reduced therapy in elderly/frail mCRC patients Elderly (≥70 years) or frail patients with metastatic colorectal cancer unsuitable for full-dose combination chemotherapy

Abstract

BACKGROUND: Fluoropyrimidines + angiogenesis inhibitor or dose-reduced doublets are used for (frail) elderly patients with metastatic colorectal cancer (mCRC). This non-comparative trial evaluated two 1st line regimens for patients not eligible for full-dose combinations. METHODS: This open-label, multicenter, phase II study randomized untreated mCRC patients ≥ 70 years ± frailty 1:1 to dose reduced mFOLFOX7 in Arm A or aflibercept (4 mg/kg) plus dose reduced mLV5FU2 in Arm B. Primary endpoint was the 6-months PFS rate (PFS@6), secondary endpoints included safety, overall survival (OS), overall response rate (ORR), patient reported outcomes and overall treatment utility (OTU). FINDINGS: The full analysis population comprised 120 patients (62 Arm A, 58 Arm B; 63% male), with a median age of 78.5 years. 82% frail patients were included. PFS@6 was 68% [95%CI 56%;80%] in Arm A and 46% [32%;59%] in Arm B. Median PFS was 7.9 and 5.5 months, median OS was 20.4 and 19.0 months and ORR was 47% and 22% in Arm A and B, respectively. At 3 months, 52% in Arm A and 35% in Arm B had a good OTU. Most frequent grade ≥ 3 AEs in Arm B were hypertension (41%) and proteinuria (10%). More patients in arm B had treatment-related SAEs grade ≥ 3 (17% in arm B and 5% in arm A). INTERPRETATION: Both regimens were feasible in this (frail) elderly population. Dose-reduced mFOLFOX7 and, to a lesser extent, 5-FU/aflibercept showed good PFS and 3-month OTU. Although most patients were regarded frail, survival rates were promising, most likely due to effective further-line treatments.