|Exelixis Announces Positive Results From Subgroup Analyses of the METEOR Phase 3 Pivotal Trial of Cabozantinib in Advanced Renal Cell Carcinoma to be Presented at ASCO 2016 Genitourinary Cancers Symposium|
-- Data further underscore clinical benefit of cabozantinib across subgroups of patients with advanced renal cell carcinoma --
-- METEOR data are the foundation for the U.S. NDA filing submitted last month, EU filing planned for early 2016 --
“In the METEOR trial, cabozantinib was previously associated with statistically significant improvements in progression-free survival and objective response rate as compared to everolimus, a standard of care in the second-line renal cell carcinoma treatment setting,” said Dr. Escudier. “This latest data set demonstrates that these benefits are favorable across a variety of prespecified and post-hoc subgroups, including patients who have received prior therapy with immune checkpoint inhibitors. In addition, cabozantinib was active in patients with low and high tumor burden, including patients with both bone and visceral metastases. Collectively, the data from METEOR suggest that cabozantinib could become an important addition to the renal cell carcinoma treatment landscape if approved.”
As previously announced, the METEOR trial met its primary endpoint of
demonstrating a statistically significant increase in 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 for this population 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 everolimus (hazard ratio [HR]=0.58, 95%
confidence interval [CI] 0.45-0.75, p<0.001). These data were later
presented at the
The ASCO GU presentation will be the first to include PFS data from the METEOR trial’s entire 658-patient study population. As assessed by independent radiology committee, the median PFS across all enrolled patients was 7.4 months for the cabozantinib arm versus 3.9 months for the everolimus arm, corresponding to a 48% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (HR = 0.52, 95% CI 0.43-0.64, p<0.001).
Updated ORR results from the full 658-patient study population will also
be presented at ASCO GU for the first time. As assessed by independent
radiology committee, the ORR across all 658 patients was 17% for
cabozantinib and 3% for everolimus. The median duration of response for
cabozantinib was not reached (95% CI 7.2 months; not reached), as
compared to 7.4 months (95% CI 1.9 months; not reached) for everolimus.
As previously reported at the ECC in
Cabozantinib’s effects on PFS and ORR were favorable across patient subgroups including: ECOG performance status; commonly applied RCC risk criteria developed by Motzer et al.; organ involvement, including bone and overall tumor burden; extent and type of prior VEGF receptor TKI therapy; and prior PD-1/PD-L1 therapy. For patients without prior PD-1/PD-L1 therapy, median PFS was 7.4 months for cabozantinib and 3.9 months for everolimus (HR = 0.54, 95% CI 0.44-0.66). For patients who had received prior PD-1/PD-L1 therapy, the median PFS for cabozantinib was not reached, and the median PFS for everolimus was 4.1 months (HR = 0.22, 95% CI 0.07-0.65).
“These new METEOR subgroup analyses further underscore the potential for
cabozantinib to significantly impact the treatment of renal cell
carcinoma, an aggressive cancer for which patients and physicians need
new options,” said
As previously reported, 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. 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.
Safety data from the trial were consistent with what was previously presented and published.
Cabozantinib is currently marketed in capsule form under the brand name
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 the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; however, the five-year survival rate for patients with advanced or late-stage metastatic RCC is under 10 percent, with no identified cure for the disease.3
Until the introduction of targeted therapies into the RCC setting a decade ago, treatments for metastatic RCC had historically been limited to cytokine therapy (e.g., interleukin-2 and interferon). In the second and later-line settings, which encompass approximately 17,000 drug-eligible patients in the U.S. and 37,000 globally,4 two small-molecule therapies and an immune checkpoint inhibitor have been approved for the treatment of patients with advanced RCC who have received prior systemic therapy. The currently approved small-molecule agents have shown little differentiation in terms of efficacy and have demonstrated only modest progression-free survival benefit in patients refractory to sunitinib, a commonly-used first-line therapy.
The majority of clear cell RCC tumors exhibit down-regulation of
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.
Cabozantinib, marketed under the brand name COMETRIQ®, is
currently approved by the
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
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
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: a future data presentation
from subgroup analyses of METEOR, including PFS data and ORR results
from the full 658-patient study population; the potential impact of
cabozantinib on the renal cell carcinoma treatment landscape, if
approved; Exelixis’ intention to include results from the subgroup
analysis of METEOR in its upcoming European Union Marketing
Authorization Application, which it expects to submit shortly; and that
the METEOR trial will continue to the final analysis of OS which is
anticipated in 2016. Words such as “planned,” “will,” “could,”
“potential,” “intend,” “expect,” “continue” “anticipated,” or other
similar expressions identify forward-looking statements, but the absence
of these words does not necessarily mean that a statement is not
forward-looking. In addition, any statements that refer to expectations,
projections or other characterizations of future events or circumstances
are forward-looking statements. These forward-looking statements are
based upon Exelixis’ current plans, assumptions, beliefs, expectations,
estimates and projections. Forward-looking statements involve risks and
uncertainties. Actual results and the timing of events could differ
materially from those anticipated in the forward-looking statements as a
result of these risks and uncertainties, which include, without
limitation: availability of clinical trial data at the referenced times;
the clinical, therapeutic and commercial potential of cabozantinib;
2 Jonasch et al., BMJ (2014) vol. 349, g4797.
4 ACS 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 (
5 Harschman and Choueiri, Cancer J. 2013 v19 316-323; Rankin et al., PNAS, 2014.
6 Bommy-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.
7 Ciamporcero et al., MolCancerTher, 2014; Rankin et al., PNAS, 2014.