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Interim Safety Data Presented on Vectibix(TM) (Panitumumab) in Combination with Standard Chemotherapy
Emerging Data From Two Phase 3 Trials Exploring Vectibix in
Earlier Lines of Colorectal Cancer Treatment
ABSTRACT NUMBERS: 335, 443, 462
ORLANDO, Fla.--(BUSINESS WIRE)--Jan. 27, 2008--Amgen (NASDAQ: AMGN) today announced interim pooled, blinded safety data from two Phase 3 trials examining Vectibix(TM) (panitumumab) in combination with chemotherapy in first- and second-lines of metastatic colorectal cancer (mCRC) treatment. The respective independent Data Monitoring Committee's reviews of the pooled, or combined, safety data from both arms of these randomized, multi-center trials endorsed the continuation of these studies per protocol. These interim data were presented today at the 2008 Gastrointestinal Cancers Symposium (ASCO GI) in Orlando, Fla.
Vectibix was approved as a monotherapy in the United States (U.S.) in September 2006 for the treatment of patients with epidermal growth factor receptor- (EGFr) expressing mCRC after disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
"We continue to make progress in elucidating the potential utility of Vectibix in the treatment of colorectal cancer," said David Chang, M.D., vice president for oncology clinical development at Amgen. "These Phase 3 studies will provide important information about the efficacy of Vectibix when used in combination with conventional chemotherapy regimens."
PRIME (203) Study
The "PRIME" (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) or "203" trial is a global Phase 3 study investigating Vectibix in combination with FOLFOX chemotherapy as a first-line treatment for patients with mCRC. Patients enrolled in the study were randomized to receive either 6.0 mg/kg of Vectibix and FOLFOX4 once every two weeks (Q2W) or FOLFOX4 alone Q2W. The primary endpoint is progression-free survival and other endpoints include overall survival, objective response rate, time to progression, duration of response and safety.
A pooled interim safety review of 601 patients (302 Vectibix plus FOLFOX; 299 FOLFOX only) of which 99 percent received at least one cycle of therapy showed the following grade 3/4 adverse events: neutropenia (25 percent), diarrhea (10 percent), fatigue (four percent), nausea and pulmonary embolism (three percent, respectively), febrile neutropenia, hypomagnesemia, dehydration and deep vein thrombosis (two percent, respectively). Fifty-four percent of the pooled patient population had a skin reaction with 11 percent of patients having a grade three and less than one percent experiencing a grade four. PRIME study's target accrual goal of approximately 1,150 patients was reached in January 2008.
The "181" trial is a global Phase 3 study investigating Vectibix in combination with FOLFIRI chemotherapy as a second-line treatment for patients with mCRC. Patients enrolled in the study were randomized to receive either 6.0 mg/kg of Vectibix and FOLFIRI Q2W or FOLFIRI Q2W alone. The co-primary endpoints are progression-free survival and overall survival, other endpoints include objective response rate, time to progression, duration of response and safety.
A pooled interim safety review for 701 patients (352 Vectibix plus FOLFIRI; 349 FOLFIRI only) of which 99 percent received at least one cycle of therapy showed the following grade 3/4 adverse events: neutropenia (15 percent), diarrhea (9 percent), fatigue (four percent), febrile neutropenia, nausea, dehydration, pulmonary embolism (two percent, respectively), hypomagnesemia and deep vein thrombosis (one percent, respectively) and infection (less than one percent). Sixty-one percent of the pooled patient population had a skin reaction with 12 percent experiencing a grade three and less than one percent experiencing a grade four. Target accrual for this study is approximately 1,100 patients and enrollment is anticipated to be complete by Q1 2008.
In both arms of each trial KRAS mutational status in patients' tumors will be studied as a biomarker for Vectibix activity. Recent data indicate that KRAS gene status may predict efficacy and could potentially serve as a patient selection biomarker for Vectibix monotherapy.
Also presented at ASCO GI were data from "STEPP" (Skin Toxicity Evaluation Protocol with Panitumumab), the first prospective study that examined differences between pre-emptive and reactive skin treatment for skin toxicities. Patients enrolled in the study either received second-line FOLFIRI-based chemotherapy plus 6.0 mg/kg of Vectibix Q2W (n=32) or irinotecan-based chemotherapy plus 9.0 mg/kg Vectibix (n=26) every three weeks (Q3W) and were randomized to pre-emptive or reactive skin treatment. Pre-emptive skin treatment included the administration of skin moisturizer, sunscreen, topical steroid, and doxycycline.
An interim analysis of 58 patients that completed 14 weeks of Vectibix treatment showed the following adverse events: 72 percent of patients had a grade three or greater adverse event in the Vectibix/FOLFIRI Q2W arm with the most notable events being neutropenia (19 percent), diarrhea and dermatitis acneiform (16 percent) and dehydration (13 percent). In the Vectibix/Irinotecan Q3W arm 50 percent of patients experienced a grade three or greater adverse event with hypokalemia (15 percent) being the most significant.
In this interim analysis the investigator assessed best overall response (complete response plus partial response) in the Vectibix plus FOLFIRI Q2W arm was 31 percent.
Vectibix is approved as a monotherapy for the treatment of patients with EGFr-expressing mCRC after disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. The effectiveness of Vectibix as a single agent 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. In December 2007, the European Medicines Agency (EMEA) granted a conditional marketing authorization for Vectibix as monotherapy for the treatment of patients with EGFr-expressing mCRC with non-mutated (wild-type) KRAS genes after failure of standard chemotherapy regimens. Regulatory applications in the rest of the world are still pending.
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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