June 26, 2008
New Data Show Preemptive Treatment May Significantly Reduce Skin Toxicities in Patients Receiving Vectibix(R) (Panitumumab)
Amgen (NASDAQ: AMGN) today announced updated results from the "STEPP" (Skin Toxicity Evaluation Protocol with Panitumumab) trial, the first prospective study to examine differences between preemptive and reactive skin treatment for skin toxicities in metastatic colorectal cancer (mCRC) patients receiving epidermal growth factor receptor (EGFr) therapy. The analysis found that preemptive treatment reduced the incidence rate of grade 2 and greater skin toxicities by over 50 percent without additional side effects when compared to reactive skin treatment. The incidence of grade 3 or greater skin toxicities were 62 percent and 29 percent in the reactive and preemptive treatment groups respectively (odds ratio (95 percent CI): 0.3 (0.1. 0.6)). These data were presented at the 10th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
In this patient population, the time to severe skin toxicity was significantly delayed by preemptive skin treatment; at 6 weeks the event- (grade 2 or greater skin toxicity) free probabilities were 70 percent and 38 percent for the preemptive and reactive arms respectively (difference: 32.2 percent (95 percent CI: 12.8, 51.7) in favor of the preemptive arm). Time-to-first-occurrence of any specific grade 2 or higher skin toxicity was also significantly delayed in the preemptive arm. The estimated median time to the first occurrence was 2.7 weeks (95 percent CI: 2.1, 6.3) in the reactive arm and it was not reached in the preemptive arm.Skin toxicity, or rash, is one of the most common side effects of EGFr inhibitors like Vectibix(R) (panitumumab). The secondary endpoints were safety and efficacy and the analysis included data from 95 patients who had the opportunity to complete 14 weeks on study. Consistent with previous results, analyses by KRAS favored the wild-type group for all efficacy endpoints.
"Since skin rash is the most common side effect of EGFr therapy, the results of the STEPP trial showing that skin rash may be controlled by a relatively simple preemptive treatment, represent a significant advancement," said David Chang, M.D., vice president for oncology clinical development at Amgen. "In addition, these data add to the growing body of evidence supporting the utility of Vectibix in combination with chemotherapy for patients with wild-type KRAS tumors."
Patients enrolled in STEPP received, at the discretion of the investigator, either second-line FOLFIRI-based chemotherapy plus 6.0 mg/kg of Vectibix every two weeks (Q2W) or irinotecan-based chemotherapy plus 9.0 mg/kg Vectibix every three weeks (Q3W) and were randomized to preemptive or reactive skin treatment. Preemptive skin treatment included the administration of skin moisturizer, sunscreen, topical steroid and oral doxycycline. The primary endpoint was the incidence of grade two or greater skin toxicities during the six-week skin treatment period. Secondary endpoints included safety and efficacy.
The analysis of 95 patients showed the following adverse events (AE): 93 percent of all patients had a Vectibix treatment-related AE; 71 percent of all patients had a grade 3/4 AE. Vectibix dose reductions due to skin toxicities occurred in eight percent of patients. Serious adverse events (SAE) were observed in 38 percent of patients and AEs caused 14 percent of patients to end treatment.
Vectibix is U.S. Food and Drug Administration (FDA) 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, mCRC 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. Vectibix is now available in 11 European countries. In the first half of 2008 Vectibix was approved by health authorities in Canada and Australia.
Important Product Safety Information - EU
Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFR) inhibitors, are experienced with nearly all patients (approximately 90 percent) treated with Vectibix. The majority of dermatological reactions are mild to moderate in nature. In clinical studies, subsequent to the development of severe dermatological reactions (including sore mouth), infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patients who have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae, and appropriate treatment promptly initiated. Severe infusion reactions occurred with Vectibix in approximately one 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.
Important Product Safety Information - US
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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