FDA OKs New Oral Drug for Refractory Colorectal Cancer

Zosia Chustecka


September 22, 2015

UPDATED September 22, 2015 // Patients with advanced colorectal cancer who are no longer responding to other therapies will now have another option, a new oral medication.

The new product, a combination of trifluridine and tipiracil (Lonsurf, Taiho Pharmaceutical Co, Ltd) has just been approved by the United States Food and Drug Administration (FDA).

It is already available in Japan, where it was approved in March 2014 for use in the treatment of unresectable advanced or recurrent colorectal cancer.

Previously known by the code name TAS-102, the product is a combination of two active ingredients ― trifluridine, a nucleoside analogue, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor, which prevents the rapid metabolism of trifluridine, thereby increasing its bioavailability.

"The past decade has brought a new understanding around colorectal cancer, in how we can both detect and treat this often devastating disease," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "But there are many patients who still need additional options, and today's approval is a testament to the FDA's commitment to work with companies to develop new drugs in disease areas where unmet needs remain," Dr Pazdur said in a statement.

The new product is indicated for use in patients with advanced/metastatic colorectal cancer who have been previously treated with chemotherapy, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and also with biologicals, including anti-VEGF products, and if the tumor was RAS wild-type, also with an anti-EGFR therapy.

Efficacy and safety were evaluated in the phase 3 RECOURSE trial, an international, randomized, double-blind study involving 800 patients with previously treated metastatic colorectal cancer. Study participants received best supportive care and were assigned to the new product or placebo, which they received until their disease worsened or side effects became intolerable.

The primary efficacy end point of the study was median overall survival, which was 7.1 months with Lonsurf vs 5.3 months with placebo (hazard ratio = 0.68; confidence interval, 0.58 - 0.81; P < .001). The secondary end point was progression-free survival, which was 2 months with Lonsurf vs 1.7 months with placebo.

"In a pivotal clinical trial, Lonsurf demonstrated that it can extend overall survival, providing patients and their oncologists with a novel oral therapy," said Robert J. Mayer, MD, faculty vice president for academic affairs at the Dana Farber Cancer Institute, professor of medicine at Harvard Medical School, and principal investigator of the RECOURSE study.

"Metastatic colorectal cancer cells often become resistant to previously effective treatment, underscoring the importance of identifying new therapeutic options for patients with the disease," Dr Mayer commented in a statement.

The FDA noted that the most common side effects of treatment with Lonsurf are anemia, neutropenia or thrombocytopenia, physical weakness, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and fever.

The manufacturer noted that in the RECOURSE study, the product caused severe and life-threatening myelosuppression (grade 3-4), consisting of anemia (in 18% of patients), neutropenia (38%), thrombocytopenia (5%), and febrile neutropenia (3.8%). One patient (0.2%) died because of neutropenic infection.

Both the FDA and the manufacturer advise that complete blood counts be obtained prior to and on day 15 of each cycle of Lonsurf, and more frequently as clinically indicated.

Healthcare providers are also encouraged to advise women of potential risks for fetotoxicity and to warn women not to breastfeed while taking the drug.


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