Department of Medicine III & Comprehensive Cancer Center, Hospital of the University (LMU) Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Int J Cancer. 2019 Jul 15;145(2):576-585. doi: 10.1002/ijc.32110. Epub 2019 Jan 24.
Panitumumab is approved for RAS wild-type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first-line randomised studies. This retrospective analysis of these trials investigated efficacy and toxicity of panitumumab-based maintenance after oxaliplatin discontinuation in RAS wild-type patients. First-line regimens were FOLFOX4 ± panitumumab in PRIME and mFOLFOX6 plus panitumumab or mFOLFOX6 plus bevacizumab in PEAK. Outcomes included median progression-free survival (PFS) and overall survival (OS), from randomisation and oxaliplatin discontinuation, and toxicity. Overall, median duration of panitumumab plus 5-fluorouracil/leucovorin (5-FU/LV) maintenance was 21 (interquartile range: 11-41) weeks; that of 5-FU/LV ± bevacizumab maintenance was 16 (6-31) weeks. Median OS from randomisation was 40.2 (95% confidence interval: 30.3-50.4) and 39.1 (34.2-63.0) months for panitumumab plus 5-FU/LV maintenance and 24.1 (17.7-33.0) and 28.9 (21.0-32.0) months for 5-FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. Median PFS from randomisation was 16.6 (11.3-23.6) and 15.4 (11.6-18.4) months for panitumumab plus 5-FU/LV maintenance and 12.6 (9.4-16.2) and 13.1 (9.5-16.6) months for 5-FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. From oxaliplatin discontinuation, median OS was 33.9 (24.7-42.8) and 33.5 (24.5-54.9) months for panitumumab plus 5-FU/LV maintenance and 16.4 (12.4-24.1) and 23.3 (15.7-26.3) months for 5-FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively; PFS was 11.7 (7.8-19.2) and 9.7 (5.8-14.8) months and 7.1 (5.6-10.2) and 7.0 (3.9-10.6) months, respectively. The most frequently reported adverse events were rash, fatigue and diarrhoea. Maintenance of panitumumab plus 5-FU/LV after oxaliplatin discontinuation was well tolerated and may be an acceptable treatment paradigm for patients demonstrating a good response to first-line treatment. Prospective studies are warranted.
帕尼单抗获批用于 RAS 野生型转移性结直肠癌，在 III 期（PRIME，NCT00364013）和 II 期（PEAK，NCT00819780）一线随机研究中进行了评估。本研究对这两项试验进行了回顾性分析，旨在探讨 RAS 野生型患者停用奥沙利铂后，接受帕尼单抗维持治疗的疗效和毒性。一线方案在 PRIME 中为 FOLFOX4±帕尼单抗，在 PEAK 中为 mFOLFOX6 联合帕尼单抗或 mFOLFOX6 联合贝伐珠单抗。结局包括无进展生存期（PFS）和总生存期（OS），分别从随机分组和奥沙利铂停药开始，并评估毒性。总体而言，帕尼单抗联合氟尿嘧啶/亚叶酸（5-FU/LV）维持治疗的中位持续时间为 21 周（四分位间距：11-41 周）；5-FU/LV±贝伐珠单抗维持治疗的中位持续时间为 16 周（6-31 周）。PRIME 和 PEAK 中，从随机分组开始，OS 中位数分别为 40.2（95%置信区间：30.3-50.4）和 39.1（34.2-63.0）个月，用于帕尼单抗联合 5-FU/LV 维持治疗；24.1（17.7-33.0）和 28.9（21.0-32.0）个月，用于 5-FU/LV±贝伐珠单抗维持治疗。PRIME 和 PEAK 中，从随机分组开始，PFS 中位数分别为 16.6（11.3-23.6）和 15.4（11.6-18.4）个月，用于帕尼单抗联合 5-FU/LV 维持治疗；12.6（9.4-16.2）和 13.1（9.5-16.6）个月，用于 5-FU/LV±贝伐珠单抗维持治疗。从奥沙利铂停药开始，OS 中位数分别为 33.9（24.7-42.8）和 33.5（24.5-54.9）个月，用于帕尼单抗联合 5-FU/LV 维持治疗；16.4（12.4-24.1）和 23.3（15.7-26.3）个月，用于 5-FU/LV±贝伐珠单抗维持治疗。PRIME 和 PEAK 中，PFS 中位数分别为 11.7（7.8-19.2）和 9.7（5.8-14.8）个月，7.1（5.6-10.2）和 7.0（3.9-10.6）个月。最常见的不良反应为皮疹、疲劳和腹泻。奥沙利铂停药后，帕尼单抗联合 5-FU/LV 的维持治疗耐受性良好，可能是对一线治疗反应良好的患者的一种可接受的治疗方案。需要开展前瞻性研究。
