Purpose

To assess whether panitumumab is active in patients with cetuximab-refractory metastatic colorectal cancer (mCRC).

Patients and Methods

Eligible patients had pretreated RAS (renin–angiotensin system) wild-type mCRC that progressed after cetuximab treatment, after having shown either objective response or stable disease. A minimax two-stage design was applied, with progression-free rate at 2 months as the primary end point. At least 12 of 28 and 21 of 41 successes at the first and second stage, respectively, were required for a positive result. Panitumumab 6 mg/kg was provided every 2 weeks, until progression or unacceptable toxicity.

Results

Overall, 52 patients with KRAS (Kirsten rat sarcoma viral oncogene) wild-type disease were enrolled, but 11 were found to have mutated disease after all-RAS retesting. Among 41 eligible patients, median time since diagnosis was 38 months, and 71% experienced an objective response to previous cetuximab. First stage was passed with 12 of 28 patients alive without progression at 2 months. At the second stage, 17 of 41 patients were alive without progression at 2 months. At a median follow-up of 21.8 months, 35 patients experienced disease progression, and 26 died. Median progression-free survival was 2.1 months (95% confidence interval, 1.8-3.6) and median overall survival 6.8 months (95% confidence interval, 4.6-16.6). Most of the patients experienced no adverse reactions; 25% of patients had grade 3 rash.

Conclusion

According to our study design, panitumumab was not effective in patients with cetuximab-refractory RAS wild-type mCRC.

中文翻译：

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帕尼单抗在西妥昔单抗难治性转移性结直肠癌患者中的多中心单臂、两阶段 2 期研究：PACER 试验。

目的

评估帕尼单抗是否对西妥昔单抗难治性转移性结直肠癌 (mCRC) 患者有效。

患者和方法

符合条件的患者已预先治疗过RAS（肾素 - 血管紧张素系统）野生型 mCRC，在西妥昔单抗治疗后进展，在表现出客观反应或疾病稳定后。应用了极小极小两阶段设计，以 2 个月的无进展率作为主要终点。分别在第一和第二阶段的 28 次成功和 41 次成功中的 21 次至少需要 12 次才能获得阳性结果。每 2 周提供一次帕尼单抗 6 mg/kg，直至出现进展或出现不可接受的毒性。

结果

总共有 52 名KRAS（Kirsten 大鼠肉瘤病毒癌基因）野生型患者入组，但发现 11 名患者在所有RAS后发生突变重新测试。在 41 名符合条件的患者中，自诊断以来的中位时间为 38 个月，71% 的患者对之前的西妥昔单抗有客观反应。第一阶段通过，28 名患者中有 12 名在 2 个月时存活且无进展。在第二阶段，41 名患者中有 17 名在 2 个月时存活且无进展。在中位随访 21.8 个月时，35 名患者出现疾病进展，26 人死亡。中位无进展生存期为 2.1 个月（95% 置信区间，1.8-3.6），中位总生存期为 6.8 个月（95% 置信区间，4.6-16.6）。大多数患者没有出现不良反应；25% 的患者出现 3 级皮疹。

结论

根据我们的研究设计，帕尼单抗对西妥昔单抗难治性RAS野生型 mCRC患者无效。