Dose-Reduced Chemotherapy Expands Treatment Options for Frail Patients with Metastatic Colorectal Cancer

Key Clinical Summary:

• Design/Population: In the phase 2 ELDERLY trial, 120 previously untreated patients ≥70 years with metastatic colorectal cancer, not eligible for full-dose combination therapy, were randomized to receive either dose-reduced mFOLFOX7 or aflibercept plus dose-reduced mLV₅FU₂.
• Key Outcomes: Dose-reduced mFOLFOX7 improved survival and response, and overall treatment utility at 3 months was higher with mFOLFOX7. Grade ≥3 adverse events and serious adverse events were more frequent with aflibercept plus dose-reduced mLV₅FU₂.
• Clinical Relevance: Dose-reduced chemotherapy represents a feasible treatment strategy for elderly, frail patients with metastatic colorectal cancer. mFOLFOX7 may be preferred given it provides better disease control.

Results from the phase 2 ELDERLY trial demonstrated that dose-reduced chemotherapy regimens show clinical activity with a manageable safety profile among elderly and frail elderly patients with metastatic colorectal cancer (mCRC). 

“Fluoropyrimidines [plus an] angiogenesis inhibitor or dose-reduced doublets are used for (frail) elderly patients with [mCRC],” stated Ralf-Dieter Hofheinz, MD, Mannheim Cancer Center, Mannheim, Germany, and coauthors. “This non-comparative trial evaluated two 1st line regimens for patients not eligible for full-dose combinations.”

In this multicenter, open-label trial, 120 previously untreated elderly or frail elderly patients with inoperable metastatic disease were randomized 1:1 to receive either dose-reduced mFOLFOX7 (n = 62) or 4 mg/kg of aflibercept plus dose-reduced mLV₅FU₂ (n = 58). The primary end point was 6-month progression-free survival (PFS). Key secondary end points included overall survival (OS), overall response rate (ORR), overall treatment utility, and safety. 

At analysis, median PFS was 7.9 months in the mFOLFOX7 arm and 5.5 months in the aflibercept plus mLV₅FU₂ arm, with corresponding 6-month PFS rates of 68% and 46%, respectively. Median OS was 20.4 months and 19 months, respectively. The ORR was 47%, including 3 complete responses and 26 partial responses in the mFOLFOX7 arm and 22%, including 1 complete response and 12 partial responses in the aflibercept plus mLV₅FU₂ arm. 

Overall treatment utility was assessed at 3 (n = 40; n = 30) and 6 months (n = 25; n = 18). At 3 months, good overall treatment utility was observed in 52% of patients in the mFOLFOX7 arm and 25% of patients in the aflibercept plus mLV₅FU₂ arm. At 6 months, good overall treatment utility was observed in 27% and 21% of patients, respectively. 

Grade ≥3 treatment-related adverse events were reported in 36% of patients in the mFOLFOX7 arm and 53% of patients in the aflibercept plus mLV₅FU₂ arm, and most commonly hypertension (41%) and proteinuria (10%). Serious adverse events reported in 31 patients in the mFOLFOX7 arm and 45 patients in the aflibercept plus mLV₅FU₂ arm. Serious treatment-related colonic perforation led to 1 death in the aflibercept plus mLV₅FU₂ arm. 

“Both regimens were feasible in this (frail) elderly population,” concluded Dr Hofheinz et al. “Although most patients were regarded frail, survival rates were promising, most likely due to effective further-line treatments.” 

Source:

Hofheinz RD, Von Weikersthal LF, Dechow T, et al. 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). Eur J Cancer. Published online: March 24, 2026. doi:10.1016/j.ejca.2026.116689