Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Department of Oncology, Tom Baker Cancer Center, University of Calgary, 1331 29 Street NW, Calgary, AB, T2N4N2, Canada.
Med Oncol. 2018 Jun 23;35(8):114. doi: 10.1007/s12032-018-1176-6.
The CORRECT trial demonstrated survival benefits with regorafenib monotherapy in patients with treatment-refractory, metastatic colorectal cancer (mCRC). However, the trial's stringent eligibility criteria for regorafenib may limit its external validity. We aimed to examine treatment attrition rates and eligibility for regorafenib in routine practice. We identified patients at the British Columbia Cancer Agency diagnosed with mCRC who demonstrated disease progression or intolerable toxicity on 2 or more lines of systemic therapy. During the study timeframe, panitumumab and cetuximab were only used in the chemo-refractory setting. Data on clinicopathologic variables and patient outcomes were ascertained and analyzed. Eligibility was determined using the CORRECT trial criteria. A total of 391 patients were identified, among whom only 39% were eligible for regorafenib: 35% in the panitumumab group and 51% in the cetuximab group. The main reasons for ineligibility in all patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1 (69%), an elevated total bilirubin (21%), and thromboembolic events in the past 6 months (10%). No difference in eligibility for regorafenib was observed between patients previously receiving panitumumab or cetuximab (P = 0.914; 95% CI 0.550-1.951). Kaplan-Meier analyses showed that regorafenib-eligible compared to regorafenib-ineligible patients had an increased median overall survival of 5.3 versus 2.1 months, respectively (P < 0.001). However, Cox proportional hazard analyses showed that only ECOG PS rather than trial eligibility was correlated with outcomes. The strict eligibility criteria disqualify most patients with treatment-refractory mCRC for regorafenib therapy. Future trials should broaden the eligibility criteria to improve external validity.
CORRECT 试验表明，在治疗耐药的转移性结直肠癌（mCRC）患者中，regorafenib 单药治疗具有生存获益。然而，该试验中regorafenib 的严格纳入标准可能限制了其外部有效性。我们旨在检查常规实践中的治疗脱落率和 regorafenib 的纳入标准。我们确定了在不列颠哥伦比亚癌症署被诊断为 mCRC 的患者，这些患者在接受 2 线或以上的系统治疗后出现疾病进展或不可耐受的毒性。在研究期间，panitumumab 和 cetuximab 仅在化疗耐药的情况下使用。我们确定了临床病理变量和患者结局的数据，并进行了分析。使用 CORRECT 试验标准确定纳入标准。共确定了 391 例患者，其中只有 39%符合 regorafenib 的纳入标准：panitumumab 组为 35%，cetuximab 组为 51%。所有患者中不符合纳入标准的主要原因是东部肿瘤协作组表现状态（ECOG PS）>1（69%）、总胆红素升高（21%）和 6 个月内发生血栓栓塞事件（10%）。既往接受 panitumumab 或 cetuximab 治疗的患者之间，regorafenib 的纳入标准无差异（P=0.914；95%CI 0.550-1.951）。Kaplan-Meier 分析显示，与 regorafenib 不可纳入的患者相比，regorafenib 可纳入的患者的中位总生存期分别增加了 5.3 个月和 2.1 个月（P<0.001）。然而，Cox 比例风险分析表明，只有 ECOG PS 而不是试验纳入标准与结局相关。严格的纳入标准使大多数治疗耐药的 mCRC 患者不符合 regorafenib 治疗的条件。未来的试验应放宽纳入标准，以提高外部有效性。
