Press Release
Press Release
Exelixis Announces Positive Results from METEOR Phase 3 Pivotal Trial of Cabozantinib in Advanced Renal Cell Carcinoma Presented at European Cancer Congress 2015
– Cabozantinib met the primary endpoint of improving progression-free survival as compared to everolimus –
– Cabozantinib showed a strong trend towards improving overall survival as compared to everolimus at an interim analysis –
– Results will be presented during ECC 2015 Presidential Session I
and have been published in
– U.S. and EU regulatory filings anticipated by end of 2015 and early 2016, respectively –
–
As announced in July, the METEOR trial met its primary endpoint of demonstrating a statistically significant increase in progression-free survival (PFS) for cabozantinib as compared to everolimus, as determined by an independent radiology committee. Per the trial protocol, the primary analysis was conducted among the first 375 patients randomized to ensure sufficient follow up and a PFS profile that would not be primarily weighted toward early events. The median PFS was 7.4 months for the cabozantinib arm versus 3.8 months for the everolimus arm, corresponding to a 42% reduction in the rate of disease progression or death for cabozantinib as compared to the everolimus arm (hazard ratio [HR]=0.58, 95% confidence interval [CI] 0.45-0.75, p<0.001). Cabozantinib effects were favorable across patient stratification subgroups including the number of prior VEGF receptor TKI therapies and commonly applied RCC risk criteria developed by Motzer et al.
In a post-hoc subset analysis of patients who had received sunitinib, the most commonly used first-line therapy, as their only prior VEGF receptor TKI, the median PFS for cabozantinib-treated patients (n=76) was 9.1 months versus 3.7 months for everolimus-treated patients (n=77). This corresponds to a 59% reduction in the rate of disease progression or death for patients treated with cabozantinib (HR=0.41, 95% CI 0.28-0.61).
“In the METEOR trial, cabozantinib significantly improved
progression-free survival as compared to everolimus, a commonly-used
standard of care, in both the full study population for the primary
endpoint analysis as well as in the subgroup of patients previously
treated with sunitinib only. Cabozantinib was also associated with a
safety profile similar to other VEGF receptor TKIs used to treat renal
cell carcinoma,” said
Data pertaining to overall survival (OS) in the entire study population of 658 patients, a secondary endpoint of the trial, were immature at the data cutoff. As previously announced, a pre-specified interim analysis triggered by the primary analysis for PFS showed a strong trend in OS favoring cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005) At the time of the interim analysis, the p-value of 0.0019 to achieve statistical significance was not reached, and the trial will continue to the final analysis of OS anticipated in 2016. Objective response rate, another secondary endpoint, was significantly higher with cabozantinib (21%) as compared with everolimus (5%; p < 0.001). Treatment discontinuations for adverse events unrelated to progressive disease were 9% and 10% for cabozantinib and everolimus, respectively.
“These results from the METEOR trial suggest that cabozantinib has the
potential to become a new and differentiated treatment option for
patients with renal cell carcinoma who have progressed following VEGF
receptor tyrosine kinase therapy, the most commonly-utilized treatment
in the first-line setting,” said
653 patients were evaluable for safety. Median duration of exposure was 7.6 months for cabozantinib and 4.4 months for everolimus. Investigators employed dose reductions to manage adverse events (AE), and 60% of patients on the cabozantinib arm and 25% of patients on the everolimus arm had dose reductions. The median average daily dose was 44 mg for cabozantinib and 9 mg for everolimus. The incidence of adverse events (any grade), regardless of causality, was 100% with cabozantinib and more than 99% with everolimus. Serious adverse events occurred in 40% of cabozantinib patients and 43% of everolimus patients. The most common AEs regardless of causality, grade 3 or higher, for cabozantinib were: hypertension (15%), diarrhea (11%), fatigue (9%), and hand-foot syndrome (8%). The most common AEs regardless of causality, grade 3 or higher, for everolimus were: anemia (16%), fatigue (7%), hyperglycemia (5%), and dyspnea (4%). Grade 5 adverse events occurred in 6.6% of patients in the cabozantinib arm and in 7.8% of patients in the everolimus arm, and were primarily related to disease progression. Treatment-related grade 5 events occurred in one patient (0.3%; death not otherwise specified) in the cabozantinib arm and 2 patients (0.6%; aspergillus infection and aspiration pneumonia) in the everolimus arm.
Cabozantinib is currently marketed in capsule form under the brand name
COMETRIQ® in
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About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2015 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in
Treatments for advanced RCC had historically been limited to cytokine therapy (e.g., interleukin-2 and interferon) until the introduction of targeted therapies into the RCC setting a decade ago. In the second and later-line setting, which encompasses approximately 17,000 drug-eligible patients in the U.S. and 37,000 globally,4 two therapies have been approved for the treatment of patients who have received prior VEGF receptor TKIs. However, despite the availability of several therapeutic options, currently approved agents have shown little differentiation in terms of efficacy and have demonstrated only modest PFS benefit in patients refractory to sunitinib, a commonly-used first-line therapy.
The majority of clear cell RCC tumors exhibit down-regulation of
About Cabozantinib
Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGF receptors, AXL, and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.
COMETRIQ® (cabozantinib capsules) is currently approved by
the
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
- Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.
- Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.
- COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.
- Wound complications have been reported with COMETRIQ.
- COMETRIQ treatment results in an increase in hypertension.
- Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.
- Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients treated with COMETRIQ.
- The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.
- Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.
- Avoid administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors.
- COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment.
- COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.
Please see full U.S. prescribing information, including Boxed WARNINGS, at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf
Please refer to the full European Summary of Product Characteristics for
full
About
Forward-Looking Statements
This press release contains forward-looking statements that are subject
to risk and uncertainty, including, without limitation, cabozantinib’s
potential as a new and differentiated treatment option for RCC patients
whose disease has progressed following VEGF receptor-targeting therapy;
that the METEOR trial will continue to the final analysis of OS in 2016;
and that
1Cancer Facts & Figures 2015.
2Jonasch et al., BMJ (2014) vol. 349, g4797.
3http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-survival-rates
4ACS Cancer Facts and Figures 2015; Heng et al., Ann
Oncol (2012) vol. 23 no. 6; internal data on file; Motzer et al., N Engl
J Med (2007) vol. 356 no. 2; NCIN (
5Harschman and Choueiri, Cancer J. 2013 v19 316-323; Rankin et al., PNAS, 2014.
6Bommy-Reddi et al., PNAS, 2008; Gibney et al., Ann. Oncol. 2013 v24 343-349; Koochekpour et al., Mol. Cell. Biol. 1999, v19 5902-5912; Rankin et al., PNAS, 2014.
7Ciamporcero et al., MolCancerTher, 2014.
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Source:
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Exelixis, Inc.
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Hubbard, 650-837-8194
Investor Relations and
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For Exelixis, Inc.
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