The Food and Drug Administration has given Cometriq (cabozantinib) Fast Track status for the treatment of patients with advanced renal cell carcinoma (RCC) who have received one prior therapy.
Cometriq, made by Exelixis, inhibits the activity of multiple tyrosine kinases including MET, VEGFRs, and RET. Cometriq is being investigated in the ongoing Phase III METEOR pivotal pivotal trial in patients with metastatic RCC who have had disease progression following treatment with at least one VEGFR tyrosine kinase inhibitor. Patients are randomized 1:1 to receive 60 mg of Cometriq daily or 10 mg of everolimus daily.
The primary endpoint of the trial is progression-free survival, and secondary endpoints are overall survival and objective response rate. The company notes in a news release that "top-line" results from the trial are expected to be released in the second quarter of this year, and that the drug is also being investigated in a Phase III trial called CELESTIAL in second-line hepatocellular carcinoma.
Until relatively recently, treatments for metastatic RCC were considered limited to immunotherapy such as interleukin-2 and interferon. But with the introduction of targeted therapies for RCC about 10 years ago, four new therapies became available in the last five years, but with efficacy results that were generally the same. Moreover, there have been only modest improvements in progression-free survival in patients refractory to sunitinib, the commonly used first-line therapy.
Cometriq is already approved for treatment of progressive, metastatic medullary thyroid cancer.
The drug has serious and sometimes fatal side effects: gastrointestinal perforations and fistulas; severe and sometimes fatal hemorrhage; increased thrombotic events including heart attacks; wound complications; increased hypertension; osteonecrosis of the jaw; palmar-plantar erythrodysesthesia syndrome; and kidney problems. Other adverse effects include reversible posterior leukoencephalopathy syndrome, diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation.
The most common laboratory abnormalities are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.