In metastatic colorectal cancer (mCRC), after a first-line induction with doublet/triplet chemotherapy plus bevacizumab, fluoropyrimidine+bevacizumab is the recommended maintenance option. The combination of anti-EGFR agents and chemotherapy is a guideline-endorsed first-line option for RAS/BRAF wild-type (wt) mCRC patients, but the optimal maintenance schedule has not been defined, yet. The Valentino trial showed that, after 4-month FOLFOX+panitumumab induction, single-agent panitumumab induced inferior progression-free survival (PFS) than FUFA+panitumumab, though slightly reducing toxicity. The Panama study demonstrated that, after 3-month FOLFOX+panitumumab induction, FUFA+panitumumab induced a significantly superior PFS than FUFA alone. We performed a pooled analysis of the Valentino and Panama trials including RAS wt mCRC patients who received first-line FOLFOX/panitumumab followed by a maintenance strategy. Only patients who received treatment as per-protocol (namely those who started the maintenance phase according to the assigned study treatment arm) were included. Data on patients, disease characteristics and treatment received were pooled. Patients were stratified per maintenance treatment arm considering monotherapy (FUFA or panitumumab) vs combo (FUFA+panitumumab). PFS and overall survival (OS) were calculated from the start of induction and of maintenance therapy and toxicity was evaluated by NCI CTCAE any grade and grade 3/4 adverse events (AEs) during maintenance therapy. A total of 412 patients were included in the pooled analysis, 248 and 164 from Panama and Valentino study, respectively. Overall, 123, 79 and 210 patients received maintenance with FUFA, panitumumab and FUFA+panitumumab, respectively, thus 202 patients received monotherapy and 210 combo. Baseline patients and disease characteristics were well balanced between the 3 arms except for ECOG PS, with a higher rate of ECOG PS 0 in panitumumab only arm. When calculating survival outcomes from the start of maintenance therapy, PFS was significantly superior in combo versus monotherapy arm (median PFS: 9.0 versus 5.8 months; HR 0.77, 95% CI 0.63-0.95; P=0.016), while OS showed a non-significant consistent trend (median OS: 28.0 versus 26.1; HR 0.87, 95% CI 0.68-1.11; P=0.258). The safety profile was consistent with the singular trial reports, with an increase of grade 3/4 AEs in the combo arm (25%, 20% and 42% in FUFA, panitumumab and FUFA+panitumumab arms, respectively). This pooled analysis including two randomized phase II trials showed that a combination schedule with 5-FU plus folinic acid and panitumumab is superior in PFS with a consistent trend in OS as compared to single-agent maintenance. The results mirror the available evidence on the guideline-recommended maintenance strategy after bevacizumab-based first-line therapy. Updated results might be presented at the meeting.
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