The drug rogaratinib is well tolerated and effective at treating several types of cancer, according to a study published in The Lancet Oncology
To conduct this study, researchers performed a phase 1 dose-escalation and dose-expansion study that tested rogaratinib in adults with advanced cancers across 22 sites in Germany, Switzerland, South Korea, Singapore, Spain, and France. The population of interest were aged 18 years or older and were deemed eligible for standard therapy. They were required to have an Eastern Cooperative Oncology Group performance score of 0-2, a life expectancy of at least three months, and at least one measurable lesion in accordance with the first version of Response Evaluation Criteria in Solid Tumors (RECIST).
In the dose escalation phase, the researchers orally administered rogaratinib twice daily at 50-800 mg continuously in 21-day cycles. In the dose-expansion phase, all the study participants were given an archival formalin-fixed paraffin embedded (FFPE) tumor biopsy during screening for evaluating FGFR1-3 mRNA expression. The research team supplied rogaratinib at the recommended dose for expansion to patients in four different cancer cohorts: urothelial carcinoma, head and neck squamous-cell cancer (HNSCC), non-small-cell lung cancer (NSCLC), and other solid tumor types.
The study’s key outcomes were safety and tolerability, determination of maximum tolerated dose including dose-limiting toxicities and determination of recommended phase 2 dose, and pharmacokinetics of rogaratinib. Patients who were administered at least one dose of rogaratinib were evaluated for safety, and those who completed one cycle of the drug of discontinued its use were included in the phase 2 analysis. In total, between Dec 30, 2013, and July 5, 2017, 866 patients were screened for FGFR mRNA expression, of whom 126 patients were treated.
[Articles] Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study: Rogaratinib was well tolerated and clinically active against several types of cancer. Selection by FGFR… https://t.co/mYWOUi2VGm #Cancer
— Cancer News (@Cancer_bio) August 9, 2019
The findings of the study found that among the test subjects, no dose-limiting toxicities were reported, and the maximum tolerated dose was not reached. Overall, 800 mg twice daily was established as the recommended phase 2 dose and was selected for the dose-expansion phase. Moreover, the most common adverse events were hyperphosphatasemia (61%), diarrhea (52%); and the most common grade 3–4 adverse events were fatigue (9%) and asymptomatic increased lipase (8%).
Furthermore, according to the researchers, “serious treatment-related adverse events were reported in five patients (decreased appetite and diarrhea in one patient with urothelial carcinoma, and acute kidney injury [NSCLC], hypoglycemia [other solid tumors], retinopathy [urothelial carcinoma], and vomiting [urothelial carcinoma] in one patient each); no treatment-related deaths occurred.”
In their conclusion, the researchers wrote that “selection by FGFR mRNA expression could be a useful additional biomarker to identify a broader patient population who could be eligible for FGFR inhibitor treatment.”
Great effort by close friends:
Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study https://t.co/F6IAPc9ESZ
— Prof. Dr. Boris Hadaschik (@ProfHadaschik) August 12, 2019