FLASCO / FDA Approves New Oral Medication to Treat Patients with Advanced Colorectal Cancer

FLASCO
September 23, 2015
Drugs, News

FDA Approves New Oral Medication to Treat Patients with Advanced Colorectal Cancer

The U.S. Food and Drug Administration today approved Taiho Oncology’s Lonsurf (a pill that combines two drugs, trifluridine and tipiracil) for patients with an advanced form of colorectal cancer who are no longer responding to other therapies.

“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.”

Colorectal cancer is the third most common non-skin cancer in men and women in the U.S., according to the National Cancer Institute. While still the second leading cause of cancer-related death in the U.S., over the past 10 years the number of colorectal cancer cases and related deaths have decreased, due in part to screenings, such as colonoscopies.

Lonsurf is an oral medication intended to treat patients with advanced (metastatic) colorectal cancer who have been previously treated with chemotherapy and biological therapy.

The efficacy and safety of Lonsurf were evaluated in an international, randomized, double-blind study involving 800 patients with previously treated metastatic colorectal cancer.

Study participants received Lonsurf plus best supportive care, or placebo plus best supportive care until their disease worsened or side effects became intolerable. The primary endpoint of the study was overall survival and the secondary endpoint was progression-free survival. Patients treated with Lonsurf lived an average of 7.1 months compared to 5.3 months for those treated with placebo. On average, the time to disease progression was two months for patients on Lonsurf compared to 1.7 months for patients receiving placebo.

The approval was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled trial (TPU-TAS-102-301). A total of 800 patients with previously treated metastatic colorectal cancer were randomly allocated (2:1) to receive trifluridine/tipiracil (N=534) plus best supportive care (BSC) or matching placebo (N=266) plus BSC. Key eligibility criteria included ECOG 0-1, absence of brain metastasis, and absence of ascites requiring drainage in the past four weeks. Patients received 35 mg/m² trifluridine/tipiracil (based on trifluridine component) or matching placebo orally twice daily on days 1 – 5 and 8 – 12 of each 28-day cycle until disease progression or unacceptable toxicity.

A statistically significant improvement in OS was demonstrated (HR 0.68 (95% CI: 0.58, 0.81), p<0.001, stratified log-rank test]; the median OS was 7.1 and 5.3 months in the trifluridine/tipiracil and placebo arms, respectively. PFS was also improved in patients randomly allocated to receive trifluridine/tipiracil (HR 0.47 (95% CI: 0.40, 0.55), p<0.001, stratified log-rank test).

The most common adverse drug reactions or laboratory abnormalities were anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia. The most common adverse reactions leading to dose reduction were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.

The recommended dose and schedule for trifluridine/tipiracil is 35 mg/m² (based on trifluridine component) orally twice daily within one hour of completion of morning and evening meals on days 1 through 5 and days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.

Full prescribing information is available at:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207981s000lbl.pdf

The most common side effects of treatment with Lonsurf are anemia, a decrease in infection-fighting white blood cells (neutropenia) or blood platelets (thrombocytopenia), physical weakness, extreme tiredness and lack of energy (fatigue), nausea, decreased appetite, diarrhea, vomiting, abdominal pain and fever.

The FDA recommends that health care providers obtain complete blood counts prior to starting each treatment cycle of Lonsurf and monitor patients throughout treatment, as Lonsurf may cause a severe decrease in blood cell and platelet production (myelosuppression).

Healthcare providers are also encouraged to advise women of potential risks to developing fetuses when taking Lonsurf. Women who are taking Lonsurf should not breastfeed.

Lonsurf is manufactured by Taiho Oncology Inc. in Princeton, New Jersey.