A phase II trial of alternating mXELOX/mXELIRI plus bevacizumab (BEV) as first-line treatment for metastatic colorectal cancer (mCRC).

3574 Background: First-line fluoropyrimidine (FL), oxaliplatin (OX), irinotecan (IRI) plus BEV had better efficacy but worse safety vs FL, IRI plus BEV for mCRC. Preliminary data showed promising anti-tumor activity and acceptable toxicity of alternating FL plus OX and FL plus IRI. This study aimed to assess the alternating schedule of modified capecitabine (XEL), OX (i.e., mXELOX) plus BEV and modified XEL, IRI (i.e., mXELIRI) plus BEV for mCRC. Methods: This single-arm phase II trial was conducted in China. Patients aged 18–75 years, with histologically confirmed unresectable mCRC, ≥one measurable lesion via RECIST v1.1, ECOG PS of 0 to 2, and life expectancy of ≥3 months were eligible. Prior systemic therapies were not allowed except adjuvant chemotherapy. Induction treatment consisted of XEL 1000 mg/m 2 bid D2–8 and D16–22, OX 85 mg/m 2 D1, IRI 150 mg/m 2 D15, and BEV 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). XEL 1000 mg/m 2 bid D2–15 and BEV 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. The primary endpoint was progression-free survival (PFS). Results: Between Apr 2020 and May 2023, 52 patients were included. As of Dec 30, 2023, median follow-up was 25.0 months. Mean age was 58.5±9.1 years old. 28 (54%) were male. 45 (87%) patients had either right-sided diseases, RAS or BRAF mutations. Median PFS was 11.0 months (95% CI 9.0–12.4). Subgroup analyses showed prior treatments, tumor locations and metastases, and BRAF mutations did not affect efficacy. RAS wild-type patients had longer PFS vs mutant patients (median 12.3 months vs 9.8 months; P=0.024). Objective response rate and disease control rate were 73% (59%–84%) and 94% (84%–99%), respectively. Overall survival (OS) reached 28.1 months (18.4–34.0). Efficacy data were detailed in the Table. Grade 3–4 treatment-related adverse events (TRAE) occurred in 17 (33%) of 52 patients. No treatment-related death was reported. The most common grade 3–4 TRAE were hypertension (13 [25%]), neutrophil count decreased (three [6%]), and hand-foot syndrome (two [4%]). Additionally, grade 3–4 TRAE of diarrhoea occurred in one [2%] patient and no grade 3–4 peripheral neuropathy was reported. Conclusions: Alternating mXELOX/mXELIRI plus BEV demonstrated promising anti-tumor activity against mCRC, with acceptable tolerability and no new safety signal. Further studies were warranted to confirm the efficacy of the regimen. Clinical trial information: NCT04324476 . [Table: see text]