Tsuji Akihito, Nakamura Masato, Watanabe Takanori, Manaka Dai, Matsuoka Hiroshi, Kataoka Masato, Takeuchi Masahiro, Ichikawa Wataru, Fujii Masashi
Department of Clinical Oncology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan.
Target Oncol. 2021 Nov;16(6):753-760. doi: 10.1007/s11523-021-00845-y. Epub 2021 Oct 31.
Regorafenib and trifluridine/tipiracil are standard third-line chemotherapies for colorectal cancer patients, but their efficacy is limited. Anti-epidermal growth factor receptor antibody rechallenge has been reported to be promising for patients who have obtained clinical benefit from first-line cetuximab-based chemotherapy. Moreover, panitumumab showed non-inferior efficacy to cetuximab.
This study assessed the efficacy and safety of third-line panitumumab rechallenge in patients with metastatic KRAS exon 2 wild-type metastatic colorectal cancer who obtained clinical benefit from first-line panitumumab-based chemotherapy.
This was a prospective, multicenter, phase II trial conducted from October 2013 to August 2017. Major eligibility criteria included KRAS exon 2 wild-type and achievement of complete response, partial response, or continued stable disease for at least 6 months in first-line panitumumab-based therapy. Irinotecan plus panitumumab treatment was continued until disease progression or unacceptable toxicity was observed. The primary endpoint was the 3-month progression-free survival (PFS) rate.
Twenty-five patients were enrolled in this study. Their median age was 66.5 years, and the 3-month PFS rate was 50.0% (95% confidence interval 30.0-70.0). The median PFS and overall survival were 3.1 months and 8.9 months, respectively. The response rate and disease control rate were 8.3% and 50.0%, respectively. Common grade 3/4 adverse events were acneiform rash (17%), hypomagnesemia (13%), and dry skin (13%). No treatment-related deaths occurred.
Irinotecan plus panitumumab rechallenge is a promising third-line treatment regimen in patients with metastatic wild-type KRAS colorectal cancer.
UMIN000015916.
瑞戈非尼和曲氟尿苷/替匹嘧啶是结直肠癌患者的标准三线化疗药物，但其疗效有限。据报道，对于从一线基于西妥昔单抗的化疗中获得临床获益的患者，再次使用抗表皮生长因子受体抗体具有前景。此外，帕尼单抗显示出与西妥昔单抗非劣效的疗效。
本研究评估了在一线基于帕尼单抗的化疗中获得临床获益的KRAS外显子2野生型转移性结直肠癌患者中，三线再次使用帕尼单抗的疗效和安全性。
这是一项于2013年10月至2017年8月进行的前瞻性、多中心、II期试验。主要入选标准包括KRAS外显子2野生型，以及在一线基于帕尼单抗的治疗中达到完全缓解、部分缓解或疾病持续稳定至少6个月。继续使用伊立替康加帕尼单抗治疗，直至观察到疾病进展或出现不可接受的毒性。主要终点是3个月无进展生存期（PFS）率。
本研究共纳入25例患者。他们的中位年龄为66.5岁，3个月PFS率为50.0%（95%置信区间30.0 - 70.0）。中位PFS和总生存期分别为3.1个月和8.9个月。缓解率和疾病控制率分别为8.3%和50.0%。常见的3/4级不良事件为痤疮样皮疹（17%）、低镁血症（13%）和皮肤干燥（13%）。未发生与治疗相关的死亡。
伊立替康加帕尼单抗再次治疗是转移性野生型KRAS结直肠癌患者有前景的三线治疗方案。
UMIN000015916。
