FDA Approval of CABOMETYX™ (Cabozantinib) Tablets for Patients with Advanced Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy
– CABOMETYX is the first therapy to demonstrate improved overall survival, progression-free survival and objective response rate in a large, randomized phase 3 trial of patients with advanced kidney cancer –
U.S. Food and Drug Administration (FDA) has approved CABOMETYX™ (cabozantinib) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. RCC is the most common form of kidney cancer in adults. CABOMETYX, which was granted Fast Track and Breakthrough Therapy designations by the FDA, is the first therapy to demonstrate in a phase 3 trial for patients with advanced RCC, robust and clinically meaningful improvements in all three key efficacy parameters — overall survival, progression-free survival and objective response rate.
CABOMETYX™ Tablets 20 mg, 40 mg, 60 mg
CABOMETYX™ Tablets 20 mg, 40 mg, 60 mg
“With today’s announcement, patients with previously treated advanced kidney cancer now have a new option, the first and only approved product demonstrated to help patients live longer while also delaying the progression of their cancer,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We are proud to bring new hope to this community, who are looking for more therapies that can help extend lives. Exelixis is committed to making CABOMETYX available to patients in need within the next couple weeks.”
“The efficacy profile demonstrated by CABOMETYX in the METEOR trial, now complemented by the overall survival benefit, is highly compelling,” said Toni Choueiri, MD, Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. “CABOMETYX is distinct from other approved treatment options, as it targets multiple tyrosine kinases involved in the development of RCC, including MET, AXL and three VEGF receptors. At the same time, physicians are very familiar with this class of drug and how to use dose adjustments to balance safety and efficacy. The approval of CABOMETYX is wonderful news for physicians who are looking for a new option for their previously treated patients with advanced kidney cancer.”
The approval of CABOMETYX is based on results of the phase 3 METEOR trial, which met its primary endpoint of improving progression-free survival. Compared with everolimus, a standard of care therapy for second-line RCC, CABOMETYX was associated with a 42 percent reduction in the rate of disease progression or death. Median progression-free survival for cabozantinib was 7.4 months versus 3.8 months for everolimus (HR=0.58, 95% CI 0.45-0.74, P<0.0001). CABOMETYX also significantly improved the objective response rate compared with everolimus. These data were presented at the European Cancer Congress in September 2015 and published in The New England Journal of Medicine.
As announced in February 2016, CABOMETYX also demonstrated a statistically significant and clinically meaningful increase in overall survival in the METEOR trial. Compared with everolimus, CABOMETYX was associated with a 34 percent reduction in the rate of death. Median overall survival was 21.4 months for patients receiving CABOMETYX versus 16.5 months for those receiving everolimus (HR=0.66, 95% CI 0.53-0.83, P=0.0003).
The most common (frequency ≥25 percent) adverse reactions in CABOMETYX-treated patients include diarrhea, fatigue, nausea, decreased appetite, hand-foot syndrome, high blood pressure, vomiting, weight loss, and constipation. Dose reduction rates were 60 percent for CABOMETYX and 24 percent for everolimus. The rate of treatment discontinuation due to adverse reactions was low (10 percent in each arm) and consistent with that previously reported for everolimus.
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Generic Name and Formulations:
Cabozantinib 20mg, 40mg, 60mg; tabs.
Select therapeutic use: Bladder, kidney, and other urologic cancers
Indications for CABOMETYX:
Treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy.
Do not substitute with cabozantinib caps. Swallow whole. 60mg daily. Do not eat at least 2 hours before or 1 hour after dose. Continue until disease progression or unacceptable toxicity. Stop treatment at least 28 days prior to scheduled surgery (including dental). Withhold for Grade 4 adverse reactions, Grade 3 or intolerable Grade 2 adverse reactions that are unmanageable with dose reduction or supportive care. Upon improvement to Grade 1 or to baseline, reduce dose as follows: previously on 60mg daily, resume at 40mg daily; previously on 40mg daily, resume at 20mg daily; previously on 20mg daily, resume at 20mg if tolerated, otherwise discontinue. Concomitant a strong CYP3A4 inhibitor: reduce daily dose by 20mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant a strong CYP3A4 inducer: increase daily dose by 20mg; resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Max daily dose: 80mg. Mild or moderate hepatic impairment: initially 40mg once daily.
Permanently discontinue if the following occurs: unmanageable GI perforation/fistula, severe hemorrhage, serious arterial thromboembolic events (eg, MI, cerebral infarction), hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome. Recent history or risk of severe hemorrhage: do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia syndrome (PPES) develops until improvement to Grade 1; resume at reduced dose. Severe hepatic impairment: not recommended. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during and for 4 months after final dose).
Avoid concomitant strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, rifabutin, rifapentine, St. John's Wort); if unavoidable, see Adult dose.
Diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, constipation, lab abnormalities.