-- Cabozantinib, as well as the combination of cabozantinib and erlotinib, significantly improved progression-free survival and overall survival compared with erlotinib alone
Study E1512 met its primary endpoint, demonstrating significant increases in progression-free survival (PFS) for cabozantinib and the combination of cabozantinib plus erlotinib when individually compared to the erlotinib arm. The median PFS for the combination of cabozantinib and erlotinib was 4.7 months versus 1.9 months for erlotinib alone, a more than two-fold increase that corresponds to a 65% reduction in the risk of disease worsening (hazard ratio [HR]=0.35, 80% CI 0.23-0.52, p=0.0005). The median PFS for cabozantinib monotherapy was 4.2 months versus 1.9 months for erlotinib alone, a more than doubling that corresponds to a 62% reduction in the risk of disease worsening (HR=0.38, 80% CI 0.27-0.55, p=0.0004).
Overall survival was a secondary endpoint of the trial. Median OS was 13.3 months for the combination of cabozantinib and erlotinib, and 9.2 months for cabozantinib alone, as compared to 4.1 months for erlotinib alone. These results correspond to a 56% reduction in the risk of death (HR=0.44, p=0.004) for the combination of cabozantinib plus erlotinib, and a 41% reduction in the risk of death (HR=0.59, p=0.03) for the cabozantinib monotherapy arm, respectively, when individually compared to the erlotinib arm. Objective response rate, another secondary endpoint, was 8% for the combination arm (2 partial responses [PR]), 14% (4 PRs) for the cabozantinib monotherapy arm, and 3% (1 PR) for the erlotinib arm. Stable disease as a best response was observed in 47% in the combination arm and 42% in the cabozantinib monotherapy arm, compared with 17% in the erlotinib arm.
118 patients were evaluable for safety. The most common treatment-related adverse events (AEs), grade 3 or higher, for the combination arm (n=39) were: diarrhea (27%), fatigue (15%), and syncope (8%). For the cabozantinib monotherapy arm, the most common AEs, grade 3 or higher, were: hypertension (26%), fatigue (15%), mucositis (10%) and thromboembolic events (8%). The most common AEs, grade 3 or higher, for the erlotinib arm were fatigue (12%) and diarrhea (8%). Overall, the rate of grade 3 or higher worst grade adverse events was 72% in the combination arm and 67% in the cabozantinib monotherapy arm, compared with the erlotinib arm (35%).
“Despite the availability of new therapies, lung cancer continues to
pose significant clinical challenges,” said ECOG-ACRIN group co-chair
Commenting on the results,
Study E1512 enrolled 125 patients with metastatic EGFR wild-type NSCLC who had received at one or two prior chemotherapy regimens; of these, 113 patients were evaluable for efficacy and 118 patients were evaluable for safety. Patients were randomized 1:1:1 to receive erlotinib (150 mg daily), cabozantinib (60 mg daily), or the combination of erlotinib plus cabozantinib (150 mg plus 40 mg daily). Median follow up was 12.6 months. Baseline characteristics were generally well balanced between the treatment arms with the exception of a history of treated brain metastases (combination arm 25%, cabozantinib monotherapy arm 33%, and erlotinib monotherapy arm 8%) and a history of mediastinal metastases (combination arm 50%, cabozantinib monotherapy arm 56%, and erlotinib monotherapy arm 30%). The primary objective of the trial was to compare the PFS of patients on the cabozantinib and combination arms versus that of the erlotinib arm. Each comparison had 91% power to detect a PFS hazard ratio (HR) of 0.5 with a 1-sided 0.10-level test stratified on prior number of therapies and ECOG performance status.
The trial is sponsored by the
Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGFRs 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) 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.
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This press release contains forward-looking statements, including,
without limitation, statements related to: future data presentations of
for the phase 2 clinical study evaluating cabozantinib as a treatment
for EGFR wild-type NSCLC; potential future evaluation of cabozantinib in
NSCLC; the continued development and clinical, therapeutic and
commercial potential of, and opportunities for, cabozantinib as a
component of combination therapy in NSCLC; and Exelixis’ commitment to
working with its partners to evaluate such potential. Words such as
“continues,” “will,” “encouraging,” “further,” “potential,” “committed,”
“look forward,” “next steps,” 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.
Exelixis’ 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: the availability of data at the expected times; risks
related to the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical testing; the clinical, therapeutic and
commercial value of cabozantinib; the uncertain timing and level of
expenses associated with the development of cabozantinib; Exelixis’
ability and the ability of its partners to conduct clinical trials of
cabozantinib sufficient to achieve a positive completion; market
competition; changes in economic and business conditions; and other
factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
Susan Hubbard, 650-837-8194
Investor Relations and Corporate Communications
For Exelixis, Inc.
Hal Mackins, 415-994-0040