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`Phase III Data Showing Improved Survival With Jevtana® (cabazitaxel) Injection in Second-Line Advanced Prostate Cancer Published in …
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`Press Releases
`Phase III Data Showing Improved Survival With Jevtana® (cabazitaxel)
`Injection in Second-Line Advanced Prostate Cancer Published in The Lancet
`- Results of the Phase III TROPIC global study published -
`
`BRIDGEWATER, N.J., Oct. 1 /PRNewswire-FirstCall/ -- Sanofi-aventis (EURONEXT: SAN and NYSE: SNY)
`announced today that data from the Phase III TROPIC study, which was the basis for the June 2010 U.S. Food
`and Drug Administration (FDA) approval of Jevtana® (cabazitaxel) Injection, was published in the October 2,
`2010 print edition of The Lancet in an article titled "Prednisone plus cabazitaxel or mitoxantrone for metastatic
`castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial." The
`data demonstrated that Jevtana in combination with prednisone reduced the risk of death by 30% in men with
`metastatic castration-resistant prostate cancer (also known as metastatic hormone refractory prostate cancer, or
`mHRPC) whose disease progressed following treatment with a docetaxel-containing treatment regimen.
`
`"Jevtana is the first approved therapy to fill a critical gap among patients with the most advanced stage of
`prostate cancer and is the first therapeutic option for these patients shown to prolong survival," said Oliver
`Sartor, M.D., Piltz Professor for Cancer Research at Tulane Medical School, New Orleans, and North American
`principal investigator for the pivotal TROPIC trial.
`
`"Sanofi-aventis Oncology is tackling cancer on all fronts to provide new solutions that make a difference in
`patients' lives," said Debasish Roychowdhury, M.D., Senior Vice President, Head of Global Oncology, sanofi-
`aventis. "The publication of this pivotal trial in The Lancet underscores the importance of the study, which is
`the first to demonstrate an overall survival advantage in patients with metastatic hormone refractory prostate
`cancer whose disease has progressed following treatment with a docetaxel-containing treatment regimen."
`
`Results of the TROPIC study showed that the combination of Jevtana and prednisone significantly reduced the
`risk of death by 30% [HR=0.70 (95% CI: 0.59-0.83); P<0.0001], with an improvement in median overall
`survival of 15.1 months versus 12.7 months in the mitoxantrone combination arm. In addition, patients in the
`Jevtana combination arm showed a significantly higher rate of investigator-assessed tumor response (14.4 [95%
`CI: 9.6-19.3; P<0.001]) compared with those in the mitoxantrone combination arm (4.4 [95% CI: 1.6-7.2;
`P<0.001]).
`
`In the TROPIC study, the most common (greater than or equal to 10%) adverse reactions (grade 1-4) were
`neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia,
`abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysguesia, cough,
`arthralgia, and alopecia.
`
`The most common (greater than or equal to 5%) grade 3-4 adverse reactions in patients who received Jevtana
`were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia. The most common
`adverse reactions leading to treatment discontinuation in the Jevtana group were neutropenia and renal failure.
`Treatment discontinuations due to adverse drug reactions occurred in 18% of patients who received Jevtana and
`8% of patients who received mitoxantrone. Deaths due to causes other than disease progression within 30 days
`of last study drug dose were reported in 18 (5%) Jevtana patients and 3 (less than 1%) mitoxantrone-treated
`patients. The most common fatal adverse reactions in Jevtana patients were infections (n=5) and renal failure
`(n=4). One death was due to diarrhea-induced dehydration and electrolyte imbalance.
`
`About the TROPIC Trial
`
`TROPIC was conducted in 146 trial sites in 26 countries, including the U.S. This multicenter, Phase III,
`randomized registrational trial assessed 755 mCRPC patients whose disease had progressed following treatment
`with docetaxel-based chemotherapy.
`
`Patients were randomly assigned to receive cabazitaxel plus prednisone/prednisolone or mitoxantrone plus
`prednisone/prednisolone (378 and 377 patients, respectively), for up to a maximum of 10 cycles. The primary
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`Phase III Data Showing Improved Survival With Jevtana® (cabazitaxel) Injection in Second-Line Advanced Prostate Cancer Published in …
`1/23/2019
`endpoint was overall survival. Secondary endpoints included progression-free survival, tumor response rate,
`tumor progression, prostate-specific antigen (PSA) response, PSA progression, pain response, and pain
`progression. Disease progression was defined as tumor progression, PSA progression or pain progression. Other
`secondary endpoints were overall safety of cabazitaxel in combination with prednisone, pharmacokinetics of
`cabazitaxel and its metabolite in this patient population, and the effect of prednisone on the pharmacokinetics of
`cabazitaxel.
`
`About Jevtana® (cabazitaxel) Injection
`
`Jevtana, a microtubule inhibitor, is approved in combination with prednisone for the treatment of patients with
`metastatic hormone refractory prostate cancer (mHRPC) previously treated with a docetaxel-based treatment
`regimen. Jevtana is to be administered intravenously. Jevtana was granted fast track designation by the FDA in
`November 2009. The rolling new drug application (NDA) submission was completed in March 2010 and was
`granted priority review in April 2010; Jevtana was approved by the FDA less than three months later. A
`registration dossier of Jevtana is also under regulatory review by other regulatory authorities, including the
`European Medicines Agency.
`
`Important Safety Information for Jevtana
`
`WARNING
`
`Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia,
`frequent blood cell counts should be performed on all patients receiving JEVTANA®.
`JEVTANA® should not be given to patients with neutrophil counts of less than or equal to 1,500
`cells/mm3.
`Severe hypersensitivity reactions can occur and may include generalized rash/erythema,
`hypotension and bronchospasm. Severe hypersensitivity reactions require immediate
`discontinuation of the JEVTANA® infusion and administration of appropriate therapy. Patients
`should receive premedication.
`JEVTANA® must not be given to patients who have a history of severe hypersensitivity reactions
`to JEVTANA® or to other drugs formulated with polysorbate 80.
`
`
`
`
`CONTRAINDICATIONS
`
`JEVTANA should not be used in patients with neutrophil counts of less than or equal to 1,500/mm(3).
`JEVTANA is contraindicated in patients who have a history of severe hypersensitivity reactions to
`cabazitaxel or to other drugs formulated with polysorbate 80.
`
`
`
`WARNINGS AND PRECAUTIONS
`
`Neutropenic deaths have been reported
`
`Monitor blood counts frequently to determine if initiation of G-CSF and/or dosage modification is
`needed
`Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features
`
`Severe hypersensitivity reactions can occur
`
`Premedicate with corticosteroids and H2 antagonists
`Discontinue infusion immediately if hypersensitivity is observed and treat as indicated
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`Phase III Data Showing Improved Survival With Jevtana® (cabazitaxel) Injection in Second-Line Advanced Prostate Cancer Published in …
`Mortality related to diarrhea has been reported
`
`Rehydrate and treat with anti-emetics and anti-diarrheals as needed
`If experiencing grade greater than or equal to 3 diarrhea, dosage should be modified
`
`Renal failure, including cases with fatal outcomes, has been reported. Identify cause and manage
`aggressively.
`Patients greater than or equal to 65 years of age were more likely to experience fatal outcomes not related
`to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia.
`Monitor closely.
`Patients with impaired hepatic function were excluded from the randomized clinical trial
`
`Hepatic impairment is likely to increase the JEVTANA® concentrations
`JEVTANA® should not be given to patients with hepatic impairment
`
`JEVTANA® can cause fetal harm when administered to a pregnant woman
`
`There are no adequate and well-controlled studies in pregnant women using JEVTANA®
`
`
`
`ADVERSE REACTIONS
`
`Deaths due to causes other than disease progression within 30 days of last study drug dose were reported
`in 18 (5%) JEVTANA®-treated patients. The most common fatal adverse reactions in JEVTANA®-
`treated patients were infections (n=5) and renal failure (n=4)
`The most common (greater than or equal to 10%) grade 1–4 adverse reactions were anemia, leukopenia,
`neutropenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal
`pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough,
`arthralgia, and alopecia
`The most common (greater than or equal to 5%) grade 3–4 adverse reactions in patients who received
`JEVTANA® were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia
`
`
`
`Please see the accompanying full prescribing information for Jevtana, including boxed WARNING, or visit
`http://products.sanofi-aventis.us/jevtana/jevtana.pdf
`
`The Incidence of Prostate Cancer
`
`Worldwide, prostate cancer ranks third in cancer incidence and sixth in cancer mortality in men. In the U.S.,
`prostate cancer remains the second most common cause of cancer death among men after lung cancer. In 2009,
`an estimated 192,000 new cases were anticipated in the U.S., while 27,000 men were expected to have died
`from the disease. For many patients with prostate cancer, their disease continues to progress despite prior
`treatment – including surgical and/or hormonal castration followed by chemotherapy. Metastatic prostate cancer
`indicates that the cancer has spread to the lymph nodes or other parts of the body, particularly the bones.
`Castration resistant/hormone-refractory prostate cancer means that the cancer has continued to grow despite the
`suppression of male hormones that fuel the growth of prostate cancer cells. An estimated 10-20% of patients
`with prostate cancer are diagnosed when the cancer has already metastasized.
`
`About sanofi-aventis Oncology
`
`Formed in March 2010, sanofi-aventis Oncology is targeting cancer on all fronts in an effort to address unmet
`medical needs for a broad range of patients. Starting with a deep understanding of the mechanisms by which
`cancer develops, grows and spreads as well as identifying the right science early in the discovery process, the
`company employs innovative approaches to bring the right medicines to the right patients. There are currently
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`Phase III Data Showing Improved Survival With Jevtana® (cabazitaxel) Injection in Second-Line Advanced Prostate Cancer Published in …
`1/23/2019
`more than 10 compounds in development across a broad scientific platform, including cytotoxic, antimitotic,
`anti-angiogenic agents, antivascular agents, monoclonal antibodies and cancer vaccines, as well as supportive
`care therapies. Four of these compounds are now being investigated in phase III clinical studies aimed at
`multiple solid and hematologic tumors.
`
`About sanofi-aventis
`
`Sanofi-aventis U.S. is an affiliate of sanofi-aventis, a leading global pharmaceutical company that discovers,
`develops and distributes therapeutic solutions to help improve the lives of patients. Sanofi-aventis is listed in
`Paris (EURONEXT: SAN) and in New York (NYSE: SNY). For more information, visit www.sanofi-aventis.us
`or www.sanofi-aventis.com.
`
`Forward Looking Statements
`
`This press release contains forward-looking statements as defined in the Private Securities Litigation Reform
`Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These
`statements include projections and estimates and their underlying assumptions, statements regarding plans,
`objectives, intentions and expectations with respect to future financial results, events, operations, services,
`product development and potential, and statements regarding future performance. Forward-looking statements
`are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and
`similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such
`forward-looking statements are reasonable, investors are cautioned that forward-looking information and
`statements are subject to various risks and uncertainties, many of which are difficult to predict and generally
`beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from
`those expressed in, or implied or projected by, the forward-looking information and statements. These risks and
`uncertainties include among other things, the uncertainties inherent in research and development, future
`clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the
`EMA, regarding whether and when to approve any drug, device or biological application that may be filed for
`any such product candidates as well as their decisions regarding labelling and other matters that could affect
`the availability or commercial potential of such products candidates, the absence of guarantee that the products
`candidates if approved will be commercially successful, the future approval and commercial success of
`therapeutic alternatives, the Group's ability to benefit from external growth opportunities as well as those
`discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those
`listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-
`aventis' annual report on Form 20-F for the year ended December 31, 2009. Other than as required by
`applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking
`information or statements.
`
`Contact:
`
`Jack Cox
`Tel: 1 (908) 981-5280
`E-mail: jack.cox@sanofi-aventis.com
`
`
`
`US.CAB.10.09.022
`
`SOURCE sanofi-aventis
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