Avallone Antonio, Giuliani Francesco, De Stefano Alfonso, Santabarbara Giuseppe, Nasti Guglielmo, Montesarchio Vincenzo, Rosati Gerardo, Cassata Antonino, Leo Silvana, Romano Carmela, Tamburini Emiliano, Silvestro Lucrezia, Lotesoriere Claudio, Nappi Anna, Santini Daniele, Petrillo Antonella, Colombo Alfredo, Febbraro Antonio, Leone Alessandra, Mannavola Francesco, Laterza Maria Maddalena, Izzo Francesco, Sobrero Alberto, Delrio Paolo, Giannarelli Diana, Budillon Alfredo
Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italia.
Medical Oncology Irccs Giovanni Paolo II Bari and Medical Oncology San Paolo Hospital ASL, Bari, Italy.
J Clin Oncol. 2025 Mar;43(7):829-839. doi: 10.1200/JCO.24.00979. Epub 2024 Nov 22.
To investigate whether intermittent treatment after an induction phase of first-line schedule of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab (PAN) prevents or delays the onset of resistance and improves safety and compliance with treatment in patients with unresectable / wild-type (wt) metastatic colorectal cancer (mCRC).
IMPROVE (ClinicalTrials.gov identifier: NCT04425239) was an open-label, multicenter, randomized phase II noncomparative trial. Patients with unresectable / wt mCRC were randomly assigned (1:1) to receive FOLFIRI plus PAN continuously until progression (arm A) or intermittently, with treatment-free intervals (arm B) until progression on treatment, toxicity, or death. The primary end point was progression-free survival on treatment (PFSot) at 12 months. Assuming a null hypothesis of median PFSot time ≤7 months and target PFSot ≥10 months, 65 patients per arm were needed to achieve 80% power and 10% type I error, according to the binomial test.
Between May 2018 and June 2021, 69 patients were randomly assigned to arm A and 68 to arm B. The median number of treatment cycles was 13 in arm A and 16 in arm B. At a median follow-up of 43.2 months (IQR, 35.0-50.5), median PFSot was 11.2 and 17.5 months with 12-month PFSot rates of 45.7% and 58.5%, for arms A and B, respectively. The overall response rates were 68.1% and 61.2%, and median overall survival rates were 36.3 and 35.1 months in arms A and B, respectively. The overall rate of grade >2 skin PAN-related adverse events was 30.3% in arm A and 17.9% in arm B.
Intermittent FOLFIRI plus PAN after the induction phase was feasible, and the primary end point was met with reduced toxicity while allowing patients more time off treatment.
研究在氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）联合帕尼单抗（PAN）的一线方案诱导期后进行间歇治疗，是否能预防或延迟耐药的发生，并提高不可切除/野生型（wt）转移性结直肠癌（mCRC）患者的安全性及治疗依从性。
IMPROVE（ClinicalTrials.gov标识符：NCT04425239）是一项开放标签、多中心、随机II期非对照试验。不可切除/wt mCRC患者被随机分配（1:1）接受FOLFIRI联合PAN持续治疗直至疾病进展（A组），或接受间歇治疗，有治疗间期（B组），直至因治疗、毒性或死亡而疾病进展。主要终点是治疗12个月时的治疗期间无进展生存期（PFSot）。根据二项式检验，假设中位PFSot时间≤7个月的零假设成立，目标PFSot≥10个月，则每组需要65例患者才能达到80%的检验效能和10%的I型错误率。
2018年5月至2021年6月期间，69例患者被随机分配至A组，68例患者被随机分配至B组。A组的中位治疗周期数为13个，B组为16个。中位随访43.2个月（四分位间距，35.0 - 50.5）时，A组和B组的中位PFSot分别为11.2个月和17.5个月，12个月PFSot率分别为45.7%和58.5%。总缓解率分别为68.1%和61.2%，A组和B组的中位总生存期分别为36.3个月和35.1个月。A组>2级皮肤PAN相关不良事件的总发生率为30.3%，B组为17.9%。
诱导期后采用间歇FOLFIRI联合PAN治疗是可行的，达到了主要终点，毒性降低，同时让患者有更多的治疗间期。
