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
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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