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Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancerстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или ScopusДата последнего поиска статьи во внешних источниках: 4 марта 2022 г.
- Авторы: Van Cutsem By, (Van Cutsem Eric, Hidalgo Eric), (Hidalgo Manuel, Canon Manuel), (Canon Jean-Luc, Macarulla Jean-Luc), (Macarulla Teresa, Bazin Teresa), (Bazin Igor, Poddubskaya Igor), (Poddubskaya Elena, Manojlovic Elena), (Manojlovic Nebojsa, Radenkovic Nebojsa), (Radenkovic Dejan, Verslype Dejan), (Verslype Chris, Raymond Chris), Eric
- Журнал: International Journal of Cancer
- Том: 143
- Номер: 15
- Год издания: 2018
- Издательство: John Wiley & Sons Inc.
- Местоположение издательства: United States
- Первая страница: 2053
- Последняя страница: 2064
- Аннотация: Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer By Van Cutsem, Eric (Van Cutsem, Eric) Hidalgo, Manuel (Hidalgo, Manuel) Canon, Jean-Luc (Canon, Jean-Luc) Macarulla, Teresa (Macarulla, Teresa) Bazin, Igor (Bazin, Igor) Poddubskaya, Elena (Poddubskaya, Elena) Manojlovic, Nebojsa (Manojlovic, Nebojsa) Radenkovic, Dejan (Radenkovic, Dejan) Verslype, Chris (Verslype, Chris) Raymond, Eric (Raymond, Eric) ...More View Web of Science ResearcherID and ORCID (provided by Clarivate) INTERNATIONAL JOURNAL OF CANCER Volume143 Issue8 Page2053-2064 DOI10.1002/ijc.31603 PublishedOCT 15 2018 Indexed2018-09-18 Document TypeArticle Abstract The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m(2)) in 28-day cycles to identify the recommended phase II dose (RP2D) of pimasertib. In the phase II part, patients were randomised to pimasertib (RP2D) or placebo plus weekly gemcitabine (n = 88) to investigate progression-free survival (PFS), overall survival (OS) and safety. The RP2D was determined to be 60 mg BID. PFS and OS outcomes did not indicate any treatment benefit for pimasertib over placebo in combination with gemcitabine (median PFS 3.7 and 2.8 months, respectively, HR = 0.91, 95% CI: 0.58-1.42: median OS 7.3 vs. 7.6 months, respectively). KRAS status did not influence PFS or OS. The incidence of grade 3 adverse events was 91.1% and 85.7% for pimasertib/gemcitabine and placebo/gemcitabine respectively, but there was a higher incidence of ocular events with pimasertib/gemcitabine (28.9% vs. 4.8% for placebo/gemcitabine). In conclusion, no clinical benefit was observed with first-line pimasertib plus gemcitabine compared with gemcitabine alone in patients with mPaCa. Keywords Author Keywordspimasertibpancreatic cancermetastaticMEKKRASrandomised controlled trial Keywords PlusORAL MEK1/2 INHIBITORADVANCED SOLID TUMORSMSC1936369B/AS703026ADENOCARCINOMASURVIVALMETAANALYSISCOMBINATIONTRAMETINIBPATHWAYSMELANOMA Addresses 1 Univ Hosp Gasthuisberg Leuven, Gastroenterol Digest Oncol, Leuven, Belgium 2 KULeuven, Herestr 49, B-3000 Leuven, Belgium 3 Ctr Nacl Invest Oncol, Madrid, Spain 4 START Madrid, Madrid, Spain 5 Grand Hop Charleroi, Serv Oncol Hematol, Charleroi, Belgium ...more addresses Categories/Classification Research AreasOncology
- Добавил в систему: Базин Игорь Сергеевич