Targeted investigational therapy shows early promise against multiple cancer types

April 9, 2014

The investigational, oral drug BGJ398, which blocks the activity of a family of proteins called fibroblast growth factor receptors (FGFRs), showed promising anticancer activity in patients with various types of cancer driven by FGFR genetic alterations, according to the results of a phase I clinical trial presented here at the AACR Annual Meeting 2014, April 5-9.

Genetic alterations in FGFRs play a role in driving tumor growth for a subset of with a variety of cancers, including squamous cell lung carcinoma and urothelial ," said Lecia V. Sequist, M.D., M.P.H., associate professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston. "The primary purpose of this phase I, first-in-human clinical trial of BGJ398 was to look at how the drug is tolerated by patients. However, we specifically enrolled only patients with FGFR in their tumors because we predicted these patients would have the greatest chance of benefiting from the drug.

"We were very excited to see that the drug had activity against several different types of cancer, including bladder cancer, for which we have very few treatment options," added Sequist. "By showing that patients with FGFR genetic abnormalities can respond to an FGFR inhibitor, we have clearly demonstrated the value of a personalized approach to cancer therapy with a targeted agent."

Sequist and colleagues enrolled in their trial 107 patients with a tumor shown to have an FGFR genetic alteration by central or local prescreening. Most patients had squamous cell lung carcinoma or breast cancer, but patients with a variety of other cancers, including cholangiocarcinoma and urothelial cell/bladder cancer, also participated.

Forty-three patients were treated in the dose escalation phase of the trial. In the expansion phase of the trial there were three groups, or arms. In the first were 18 patients with FGFR1-amplified squamous cell lung carcinoma who received BGJ398 daily; in the second and third were 21 and 25 patients with other cancers harboring FGFR genetic alterations who received the drug daily for four weeks and daily for three weeks followed by a week off, respectively.

The researchers saw , as assessed by after treatment, in patients who participated in the dose escalation phase and received 100 mg or more of the drug per day, and among patients in all three expansion arms. They saw tumor shrinkage in patients with various types of cancer, including four of five patients with FGFR3-mutated urothelial cell cancer. For two of these patients, tumor shrinkage was more than 30 percent, which means they had an "official" partial response. One partial response in a patient with FGFR1-amplified squamous cell lung carcinoma has previously been reported. Anticancer activity was also seen for other patients with squamous cell , squamous cell head and neck cancer, breast cancer, and cholangiocarcinoma.

The most common side effect was elevated levels of the blood mineral phosphorus. According to Sequist, in this study and future studies, patients being treated with FGFR inhibitors will also need to take phosphate-lowering medications to help balance this.

"A number of phase II clinical trials are ongoing or planned, including a study in patients with the most lethal form of brain cancer, glioblastoma multiforme," said Sequist. "Work is ongoing to further identify what specific FGFR genetic alterations correlate with response to BGJ398. In this regard, given our results with the urothelial cell/bladder patients, we are actively screening these patients to look for FGFR3 genetic alterations in order to try to give them the opportunity to be treated with BGJ398."

Explore further: Study confirms fibroblast growth factor receptors as targets for pancreatic cancer treatment

Related Stories

Study confirms fibroblast growth factor receptors as targets for pancreatic cancer treatment

December 17, 2013
Proteins called fibroblast growth factor receptors (FGFRs) have been implicated in the development of pancreatic cancer, which remains difficult to treat. Researchers at Roswell Park Cancer Institute (RPCI) have now confirmed ...

Investigational anticancer drug may benefit subgroup of patients with head and neck cancer

April 8, 2014
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), the most common form of head and neck cancer, may benefit from treatment with the investigational drug dacomitinib if their cancer ...

Genomic testing links 'exceptional' drug response to rare mutations in bladder cancer

March 13, 2014
A patient with advanced bladder cancer in a phase I trial had a complete response for 14 months to a combination of the targeted drugs everolimus and pazopanib, report scientists led by a Dana-Farber Cancer Institute researcher, ...

Targeting the EGFR and FGFR cellular pathways for bile duct cancer

February 14, 2014
Researchers at the Translational Genomics Research Institute (TGen) and physicians at Mayo Clinic's Individualized Medicine Clinic have personalized drug treatments for patients with cholangiocarcinoma using genomic sequencing ...

Clinical sequencing technology identifies new targets in diverse cancers

June 7, 2013
Novel abnormalities in the FGFR gene, called FGFR fusions, were identified in a spectrum of cancers, and preliminary results with cancer cells harboring FGFR fusions suggested that some patients with these cancers may benefit ...

Phase II trial of efatutazone shows challenge of matching treatment to population

April 8, 2014
Work at the University of Colorado Cancer Center led to phase II trial of efatutazone with erlotinib in patients with refractory non-small cell lung cancer. Results are reported today at the American Association for Cancer ...

Recommended for you

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

Combining CAR T cells with existing immunotherapies may overcome resistance in glioblastomas

July 19, 2017
Genetically modified "hunter" T cells successfully migrated to and penetrated a deadly type of brain tumor known as glioblastoma (GBM) in a clinical trial of the new therapy, but the cells triggered an immunosuppressive tumor ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.