Preliminary Pre-Planned Interim Analysis Shows Negative Effect on Progression-Free Survival
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--Amgen (NASDAQ:AMGN) today announced that it has discontinued Vectibix™ (panitumumab) treatment in the PACCE trial evaluating the addition of Vectibix to standard chemotherapy and Avastin® (bevacizumab) for the treatment of first-line metastatic colorectal cancer (mCRC). The PACCE trial investigated a treatment regimen that used dual biologics combined with oxaliplatin- or irinotecan-based chemotherapy. This regimen is not currently used in clinical practice.
The decision to discontinue Vectibix treatment in the trial was based on a preliminary review of data from a pre-planned interim efficacy analysis scheduled after the first 231 events (death or disease progression). This analysis revealed a statistically significant difference in progression-free survival in favor of the control arm. An unplanned analysis of overall survival also demonstrated a statistically significant difference favoring the control arm. Additional analyses are ongoing, and Amgen plans to present the results at an upcoming scientific forum.
“Patient safety is Amgen’s top priority. For this reason, we have decided to discontinue Vectibix treatment in the PACCE trial while we complete additional analyses of these preliminary results. We had hoped that adding Vectibix to the current U.S. standard-of-care for patients newly-diagnosed with mCRC would improve outcomes without excessive added toxicity. Unfortunately, it appears that adding Vectibix to Avastin, when used in combination with oxaliplatin- or irinotecan-based chemotherapy, increased toxicity, without improving efficacy,” said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen.
Amgen has notified the FDA and study investigators that patients who are still receiving treatment in the PACCE study should discontinue Vectibix treatment. Patients will have the option of continuing per protocol treatment without Vectibix.
In January 2007, Amgen informed all investigators and regulatory authorities about safety information arising from a planned interim safety analysis of the PACCE trial. A review of the interim analysis showed an increased incidence of grade 3 severe events of diarrhea, dehydration and infections in the Vectibix-treated patients. In addition, an increased incidence of pulmonary embolism was observed in patients who received Vectibix compared with those who did not (4 percent and 2 percent, respectively). One (<1 percent) fatal event of pulmonary embolism occurred in a patient receiving Vectibix.
Amgen is continuing to explore Vectibix as a single biologic combined with chemotherapy in Phase 3 first- and second-line registrational trials. No other clinical studies are being modified at this time. However Amgen is evaluating data across all studies.
PACCE Study Design
The PACCE (Panitumumab Advanced Colorectal Cancer Evaluation) study is a Phase 3b randomized, open-label clinical trial evaluating oxaliplatin- and irinotecan-based chemotherapy and Avastin with and without Vectibix in the first-line treatment of patients with metastatic colorectal cancer. The trial is powered to show a 30 percent improvement in progression-free survival, the primary endpoint. Secondary endpoints include response rate, overall survival, duration of response and safety. The PACCE trial enrolled 1,054 patients (824 patients were randomized to receive oxaliplatin-based chemotherapy, and 230 patients were randomized to receive irinotecan-based chemotherapy) at 240 trial sites in the United States between Q1 2005 and Q3 2006.
Vectibix is indicated for the treatment of patients with epidermal growth factor receptor- (EGFr) expressing metastatic colorectal cancer after disease progression on, or following fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens. The effectiveness of Vectibix for the treatment of EGFr-expressing, metastatic colorectal carcinoma is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.
Important Product Safety Information
Dermatologic toxicities, related to Vectibix blockade of EGF binding and subsequent inhibition of EGF receptor-mediated signaling pathways, included but were not limited to dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Dermatologic toxicities were reported in 89 percent of patients treated with Vectibix and were severe in 12 percent of patients. Severe dermatologic toxicities were complicated by infection, including sepsis, septic death, and abscesses requiring incisions and drainage. Vectibix may need to be withheld or discontinued for severe dermatologic toxicities.
Severe infusion reactions occurred with Vectibix in approximately 1 percent of patients. Severe infusion reactions were identified as anaphylactic reactions, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix, they have occurred with other monoclonal antibody products. Severe infusion reactions require stopping the infusion and possibly permanently discontinuing Vectibix, depending on the severity and/or persistence of the reaction.
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Forward Looking Statement
This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen’s Form 10-K for the year ended Dec. 31, 2006, and in Amgen’s periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
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Trish Hawkins, 805-447-5631 (media, oncology)
Arvind Sood, 805-447-1060 (investors)
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