In Phase II of the international study, conducted by researchers at the Center of Texas University of cancer, treatment with oral inhibitor of FGFR erdafitinib (ERDA) was well tolerated and provided a reliable response in patients with metastatic urothelial cancer, a mutation in the FGFR3 gene.
Target therapy was effective in a subgroup of patients for whom immunotherapy previously failed, suggesting that the ERDA may provide benefit to patients without additional treatment options. The results, presented today at the Annual Meeting of the American Society of Clinical Oncology 2018 principal investigator Arlene Sifker-Radtke, genital professor of medical oncology.
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"Given the limited treatment options for urothelial cancer, we still have a long way to benefit our patients. Testing with a frequency of about 40% of the response, with the convenience of medication, of course, corresponds to his needs ", - Sikker-Radtke said.
Urothelial cancer occurs in the cells that line the inside of the bladder, ureter and urethra. According to the American Cancer Society, this year in the United States will be diagnosed with more than 81 000 cases of bladder cancer with more than 17 000 deaths from the disease.
For several decades, the standard care was urothelial oncology chemotherapy with cisplatin-based mode, but five new checkpoint inhibitors blockade has been approved in recent years, said Sifker-Radtke. However, the overall response, defined as the percentage of patients with tumor shrinkage is from 15 to 20 percent with the help of these immunotherapy, she said.
Erdafitinib - is an oral drug that blocks the activity of the FGFR proteins, including FGFR3. Genetic changes in the FGFR3 can be found in approximately 15-20 percent of patients with metastatic carcinoma of the bladder and is thought to lead to the development of the disease. In addition, tumors with mutations in the FGFR3, seems to show no signs of immune activation is growing evidence that these tumors do not respond to immunotherapy, said Sikker-Radtke.
For International Open phase II study, 99 patients were enrolled and treated with a median of five cycles optimized mode ERDA, consisting of 8 mg per day for 28 days with escalation to 9 mg in the absence of significant adverse events. All patients had metastatic or surgically unresectable urothelial cancer with a proven mutation in FGFR3 or FGFR2 or merger in FGFR3. Allowed to chemotherapy and / or inhibitors of immune checkpoint.
Treatment-related adverse events were manageable, and only 10% of patients discontinued treatment due to symptoms. There were no deaths related to treatment. The most frequent side effects were hyperphosphatemia (high blood phosphate levels) (72 patients), disease (inflammation of the mouth and lips) (54 patients) and diarrhea (37 patients).
"Treatment ERDA was very tolerable. Was reduced the number of doses and most patients were able to continue treatment, "- Sikker-Radtke said. "Even with the proof of high level of phosphates or other toxic substances usually just sufficient to carry the drug to reduce the symptoms."
ERDA primary treatment objectives consistent with 40 percent OR-indicator including a complete response, or the disappearance of tumors in three percent of patients and partial tumor shrinkage response or - 37 percent. Another 39% of patients had stable disease progression. Preliminary data from the study showed an average overall survival of 13.8 months.
Among the 22 patients who had previously received the checkpoint inhibitors blockade, ERDA treatment gave overall response in 59 percent of patients.
"In future studies, we will need confirmation, but in patients with FGFR change compared with immunotherapy may be more benefit from targeted therapies FGFR», - Sikker-Radtke said. "This is an exciting time as we head into the area of personalized therapy urothelial cancer."
In phase III study is currently underway to assess efficiency relative ERDA chemotherapy or inhibitor blockade pembrolizumaba blockade in patients with metastatic urothelial cancer and mutations of FGFR3. Based on the phase II study, the US administration by the Food and Drug Administration has granted at the beginning of this year, a breakthrough therapy for ERDA, which will accelerate the development and review of the drug for metastatic urothelial cancer.