Previous studies showed encouraging efficacy of alternating FOLFOX/FOLFIRI for metastatic colorectal cancer (mCRC). This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC. Induction treatment included capecitabine 1000 mg/m² bid D2–8 and D16–22, oxaliplatin 85 mg/m² D1, irinotecan 150 mg/m² D15, and bevacizumab 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). Capecitabine 1000 mg/m² bid D2–15 and bevacizumab 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. 52 patients were included. Median follow-up was 25.0 months. Median progression-free survival (PFS; the primary endpoint) was 11.0 months (95% CI 9.0–12.4). Subgroup analyses showed patients with neutrophil-to-lymphocyte ratio<5 or RAS wild-type disease had longer PFS (both P < 0.05). Objective response and disease control were obtained in 38 (73%; 95% CI 59%–84%) and 49 (94%; 95% CI 84%–99%), respectively. Mean depth of response, conversion and no evidence of disease rates were 46.0% ± 26.3%, 23% and 19%, respectively. Median overall survival was 28.1 months (18.4–34.0). Grade 3–4 treatment-related adverse events (TRAE) occurred in 17 (33%) 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%]). In addition, grade 3–4 TRAE of diarrhea reported in one [2%] patient and no grade 3–4 peripheral neuropathy occurred. Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC.

先前的研究表明，交替使用 FOLFOX/FOLFIRI 治疗转移性结直肠癌 （mCRC） 的疗效令人鼓舞。本 2 期试验 （NCT04324476） 旨在评估交替改良 CAPOX（卡培他滨和奥沙利铂）/改良 CAPIRI（卡培他滨和伊立替康）加贝伐珠单抗（抗 VEGF-A 抗体）在未经治疗的不可切除 mCRC 中的疗效和安全性。诱导治疗包括卡培他滨 1000 mg/m² bid D2-8 和 D16-22、奥沙利铂 85 mg/m² D1、伊立替康 150 mg/m² D15 和贝伐珠单抗 5 mg/kg D1 和 15，为期 28 天周期（最多六个周期）。卡培他滨 1000 mg/m² bid D2-15 和贝伐珠单抗 7.5 mg/kg D1 21 天周期用作维持治疗。纳入 52 例患者。中位随访时间为 25.0 个月。中位无进展生存期 （PFS;主要终点） 为 11.0 个月 （95% CI 9.0-12.4）。亚组分析显示中性粒细胞与淋巴细胞比值 <5 或 RAS 野生型疾病患者的 PFS 较长 （均 P < 0.05）。分别有 38 例 （73%;95% CI 59%-84%） 和 49 例 （94%;95% CI 84%-99%） 获得客观缓解和疾病控制。平均反应深度、转化率和无疾病证据分别为 46.0% ± 26.3% 、 23% 和 19%。中位总生存期为 28.1 个月 （18.4-34.0）。17 例 （33%） 患者发生 3-4 级治疗相关不良事件 （TRAE）。没有报告与治疗相关的死亡。最常见的 3-4 级 TRAE 是高血压 （13 [25%]）、中性粒细胞计数减少 （3 [6%]）和手足综合征 （2 [4%]）。此外，一名 [2%] 患者报告了 3-4 级腹泻 TRAE，未发生 3-4 级周围神经病变。因此，改良 CAPOX/CAPIRI 联合贝伐珠单抗交替治疗具有有希望的疗效和可接受的安全性。 该方案可能是未经治疗的不可切除的 mCRC 的新选择。