Erratum: The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma

Autor: Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Mark Yarchoan, Rachna T. Shroff, Rose Parkinson, Denise Gallagher, Nilofer S. Azad, Ashley O'Connor, Marianna Zahurak, Gary L. Rosner
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Oncology
030213 general clinical medicine
Cancer Research
Angiogenesis
VEGF receptors
Administration
Oral
Tyrosine-kinase inhibitor
angiogenesis
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
pazopanib
Receptor
Aged
80 and over
Trametinib
Sulfonamides
trametinib
biology
MEK inhibitor
Middle Aged
MAP Kinase Kinase Kinases
VEGF
MEK
3. Good health
Survival Rate
030220 oncology & carcinogenesis
Hypertension
Disease Progression
Female
Drug Eruptions
Corrigendum
cholangiocarcinoma
medicine.drug
Adult
medicine.medical_specialty
Indazoles
Pyridones
medicine.drug_class
Pyrimidinones
digestive system
Disease-Free Survival
Pazopanib
03 medical and health sciences
Internal medicine
medicine
Humans
Protein Kinase Inhibitors
neoplasms
Aged
business.industry
Cancer
Exanthema
medicine.disease
Thrombocytopenia
digestive system diseases
Pyrimidines
Receptors
Vascular Endothelial Growth Factor
030104 developmental biology
Bile Duct Neoplasms
Multicenter study
Clinical Study
030221 ophthalmology & optometry
biology.protein
Cancer research
business
RAS
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: Background: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma. Methods: In this open-label, multicentre, single-arm trial, adults with advanced unresectable cholangiocarcinoma received pazopanib 800 mg daily and trametinib 2 mg daily until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) with secondary end points including overall survival (OS), response rate, and disease control rate (DCR). Results: A total of 25 patients were enrolled and had received a median of 2 prior systemic therapies (range 1–7). Median PFS was 3.6 months (95% CI: 2.7–5.1) and the 4-month PFS was 40% (95% CI: 24.7–64.6%). There was a trend towards increased 4-month PFS as compared with the prespecified null hypothesised 4-month PFS of 25%, but this difference did not reach statistical significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3–10.2). The objective response rate was 5% (95% CI: 0.13–24.9%) and the DCR was 75% (95% CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and hypertension. Conclusions: Although the combination of pazopanib plus trametinib had acceptable toxicity with evidence of clinical activity, it did not achieve a statistically significant improvement in 4-month PFS over the prespecified null hypothesised 4-month PFS.
Databáze: OpenAIRE
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