Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
J Clin Oncol. 2022 Sep 1;40(25):2878-2888. doi: 10.1200/JCO.22.00839. Epub 2022 Jun 6.
To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for and wild-type (wt) metastatic colorectal cancer (mCRC).
TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable and wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect ≥ 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).
From September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, = .526). No differences in early tumor shrinkage rate (57%/58%, = .878) and deepness of response (median: 48%/47%, = .845) were reported, nor in R0 resection rate (25%/29%, = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, = .277).
The intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with and wt mCRC.
验证改良氟尿嘧啶、亚叶酸、奥沙利铂和伊立替康（mFOLFOXIRI）方案的化疗基础强化是否会增加氟尿嘧啶、亚叶酸和奥沙利铂的活性，当这两种方案与帕尼单抗联合用于初始治疗 和 野生型（wt）转移性结直肠癌（mCRC）时。
TRIPLETE 是一项前瞻性、开放标签、III 期试验，纳入了 435 名不可切除的 和 wt mCRC 初治患者，按 1:1 随机分为改良 FOLFOX/帕尼单抗（对照组）或 mFOLFOXIRI/帕尼单抗（实验组），最多接受 12 个周期的治疗，随后接受氟尿嘧啶/亚叶酸/帕尼单抗治疗，直至疾病进展。主要终点是根据 RECIST 1.1 评估的客观缓解率（ORR）。假设对照组的 ORR 为 60%，432 例患者提供了 90%的效能，用于双侧 χ2 检验检验异质性，双侧 α 错误为.05，以检测两组之间 ≥ 15%的差异（ClinicalTrials.gov 标识符：NCT03231722）。
从 2017 年 9 月至 2021 年 9 月，57 个意大利研究点共纳入 435 名患者（对照组/实验组：217/218）。接受 mFOLFOXIRI 联合帕尼单抗治疗的 160 名（73%）患者和接受改良 FOLFOX 联合帕尼单抗治疗的 165 名（76%）患者达到了 RECIST 缓解（比值比 0.87，95%CI，0.56 至 1.34， =.526）。两组之间早期肿瘤退缩率（57%/58%， =.878）和缓解深度（中位数：48%/47%， =.845）无差异，R0 切除率（25%/29%， =.317）也无差异。实验组和对照组的无进展生存期（中位无进展生存期：实验组 12.7 个月，对照组 12.3 个月，风险比：0.88，95%CI，0.70 至 1.11， =.277）也无显著差异。
在 和 wt mCRC 患者中，与帕尼单抗联合应用时，化疗基础强化并未在治疗活性方面提供额外获益，反而增加了胃肠道毒性。
