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Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS-mutated metastatic colorectal cancer.

Abstract：

BACKGROUND:The mitogen-activated protein kinase (MAPK) pathway has been implicated in the molecular pathogenesis of human cancers, including metastatic colorectal cancer (mCRC). This provides a rationale for the development of MAPK-targeted agents such as pimasertib. METHODS:Patients with KRAS mutant mCRC were treated in the second-line setting with FOLFIRI (5-fluorouracil/folinic acid/irinotecan) plus pimasertib. The primary objective of the safety run-in phase was to determine the maximum-tolerated dose (MTD) and the recommended phase II dose of pimasertib combined with FOLFIRI. RESULTS:Sixteen patients were enrolled in the trial. Ten and six patients were treated daily with 45 and 60 mg of pimasertib plus FOLFIRI, respectively. The MTD was considered to be 45 mg per day. The most common treatment-emergent adverse events were diarrhoea, nausea, vomiting, asthenia and skin/rash event. Of the 15 patients in the efficacy analysis group, two patients had partial response, nine patients had stable disease, three patients had progressive disease as their best overall response and one patient could not be evaluated. CONCLUSIONS:Dose escalation of pimasertib in combination with FOLFIRI was limited by toxicity. At the MTD of 45 mg per day, pimasertib was adequately tolerated in patients with mCRC and no unexpected or new safety signals or concerns were identified.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Macarulla T,Cervantes A,Tabernero J,Roselló S,Van Cutsem E,Tejpar S,Prenen H,Martinelli E,Troiani T,Laffranchi B,Jego V,von Richter O,Ciardiello F

doi

10.1038/bjc.2015.144

subject

Has Abstract

pub_date

2015-06-09 00:00:00

pages

1874-81

issue

12

eissn

0007-0920

issn

1532-1827

pii

bjc2015144

journal_volume

112

pub_type

杂志文章,多中心研究,随机对照试验

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