Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer
Open accessAbstract
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.
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A phase I/II trial found that adding the MEK inhibitor pimasertib to gemcitabine did not improve survival over gemcitabine alone.
“In a phase I/II trial, a combination of the MEK inhibitor pimasertib and gemcitabine did not give superior survival rate than gemcitabine alone (89).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [89]
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- Authors
- Van Cutsem, E., Hidalgo, M., Canon, J., Macarulla, T., Bazin, I., Poddubskaya, E., Manojlovic, N., Radenkovic, D., Verslype, C., Raymond, E., Cubillo, A., Schueler, A., Zhao, C., & Hammel, P.
- Affiliations
- Gastroenterology/Digestive Oncology University Hospitals Gasthuisberg/Leuven & KULeuven Leuven Belgium
- Spanish National Cancer Research Centre (ES)
- Grand Charleroi Hospital (BE)
- Vall d'Hebron Hospital Universitari (ES)
- Sechenov University (RU)
- Military Medical Academy (RS)
- University of Belgrade (RS)
- KU Leuven (BE)
- Medical Oncology Département Saint Joseph Hospital Paris France
- Universidad San Pablo CEU (ES)
- Merck KGaA, Darmstadt (Germany) (DE)
- EMD Serono, Inc. (United States) (US)
- Hôpital Beaujon (FR)
- ORCID
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2018-08-09
- Volume
- 143
- Issue
- 8
- Pages
- 2053-2064
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2803544044
- Cited by
- 104
- References
- 32
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 17 · 2023: 16 · 2022: 10 · 2021: 21 · 2020: 16 · 2019: 10 · 2018: 2 · 2014: 1
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- Merck KGaA, Darmstadt, Germany and EMD Serono, Inc. (NCT01016483)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- pimasertib, MEK inhibitors, gemcitabine, metastatic pancreatic adenocarcinoma, first-line therapy, recommended phase 2 dose, progression-free survival, overall survival, KRAS status, ocular adverse effects, drug safety
- MeSH terms
- Progression-Free Survival, Gemcitabine, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Female, Humans, Male, Middle Aged, Niacinamide, Pancreatic Neoplasms
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