The Randomized Phase II ARC-9 Study of Etrumadenant-Based Therapy versus Regorafenib in Patients with Previously Treated Metastatic Colorectal Cancer.

patients_and_methods

The phase II ARC-9 study, Cohort B (NCT04660812), evaluated the efficacy and safety of etrumadenant (A2a and A2b receptor antagonist), zimberelimab (anti-PD-1 mAb), FOLFOX, and bevacizumab (EZFB) versus regorafenib in patients with third-line mCRC who previously progressed on oxaliplatin- and irinotecan-containing regimens.

II期ARC-9研究，B队列（NCT04660812），评估了etrumadenant（A2a和A2b受体拮抗剂）、zimberelimab（抗PD-1单克隆抗体）、FOLFOX和贝伐珠单抗（EZFB）与瑞戈非尼相比在先前接受奥沙利铂和伊立替康方案治疗后进展的三线mCRC患者中的疗效和安全性。

Results

From September 21, 2021, to September 12, 2022, 112 patients were randomized 2:1 to EZFB (n = 75) or regorafenib (n = 37).

从2021年9月21日至2022年9月12日，共有112名患者按2:1的比例随机分为EZFB组（n=75）和瑞戈非尼组（n=37）。

As of November 13, 2023, the median survival follow-up was 20.4 months.

截至2023年11月13日，中位生存随访时间为20.4个月。

The primary endpoint of progression-free survival(PFS) was improved with EZFB (6.2 months) versus regorafenib [2.1 months; hazard ratio(HR), 0.27; 95% confidence interval(CI), 0.17-0.43; nominal P < 0.0001], as was the secondary endpoint of overall survival(OS; EZFB, 19.7 months; regorafenib, 9.5 months; HR, 0.37; 95% CI, 0.22-0.63; nominal P = 0.0003).

主要终点无进展生存期（PFS）在使用EZFB（6.2个月）时比使用瑞戈非尼有所改善[2.1个月; 风险比（HR），0.27; 95%置信区间（CI），0.17-0.43; 名义P < 0.0001]，次要终点总生存期（OS）也是如此（EZFB，19.7个月；瑞戈非尼，9.5个月；HR，0.37；95% CI，0.22-0.63；名义P = 0.0003）。

The confirmed overall response rate was 17% (90% CI, 10.6%-26.1%) with EZFB and 3% (90% CI, 0.1%-12.2%) with regorafenib.

确认的总缓解率为EZFB组17%（90%置信区间，10.6%-26.1%），而瑞戈非尼组为3%（90%置信区间，0.1%-12.2%）。

Treatment-emergent adverse events (TEAE), grade ≥3 TEAEs, and TEAEs leading to discontinuation of all study treatments were reported in 99%, 82%, and 5% of the EZFB arm and in 87%, 49%, and 17% of the regorafenib arm, respectively.

治疗相关不良事件（TEAE）、3级或以上TEAEs以及导致所有研究治疗中断的TEAEs分别在EZFB组的99%、82%和5%中报告，在瑞戈非尼组的87%、49%和17%中报告。

Conclusions

EZFB significantly improved survival outcomes compared with regorafenib in patients with mCRC as a third-line treatment, with a manageable safety profile.

与瑞戈非尼相比，EZFB在作为三线治疗的转移性结直肠癌（mCRC）患者中显著改善了生存结果，并具有可管理的安全性特征。

Further investigation is warranted, given the clinically meaningful improvements in PFS and OS.

鉴于无进展生存期（PFS）和总生存期（OS）的临床意义改善，有必要进行进一步的研究。