Letter to Healthcare Professionals - Amgen

IMPORTANT DRUG WARNING
SUBJECT:
� Limitation of use of Vectibix ® (panitumumab) in patients with KRAS mutation-positive mCRC or for whom
KRAS mCRC status is unknown
� Risk of increased mortality or toxicity with Vectibix in combination with chemotherapy
August 27, 2012
Dear Healthcare Provider,
Amgen Inc. would like to inform you of new important safety information for Vectibix. The US prescribing
information (US-PI) has been updated to include a limitation of use for patients with KRAS mutation-positive mCRC
or for whom KRAS mCRC status is unknown. The warnings and precautions section has been updated and now
includes data regarding shortened overall survival observed in patients with KRAS mutation-positive mCRC who
received Vectibix in combination with chemotherapy compared to chemotherapy alone.
Specifically, the Indications and Usage and Warnings and Precautions sections of the US-PI have been updated to
include the following:
INDICATIONS AND USAGE
Limitation of Use
Vectibix is not indicated for the treatment of patients with KRAS mutation-positive mCRC or for whom
KRAS mCRC status is unknown. Retrospective subset analyses of metastatic colorectal cancer trials have
not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or
13.
WARNINGS AND PRECAUTIONS (see bolded text for new labeling language added in this section)
Increased Mortality or Toxicity with Vectibix in Combination With Chemotherapy
Vectibix is not indicated for use in combination with chemotherapy.
In a randomized, open-label study enrolling 440 patients with KRAS mutation-positive mCRC;
evaluating Vectibix in combination with infusional 5-fluorouracil, leucovorin, and oxaliplatin
(FOLFOX) compared to FOLFOX alone as first-line therapy for mCRC, shortened overall
survival time was observed in the mutant KRAS mCRC population after 294 deaths (HR=1.24,
95% CI: 0.98-1.57).
In an interim analysis of Study 2, the addition of Vectibix to the combination of bevacizumab and
chemotherapy resulted in decreased overall survival and increased incidence of NCI-CTC grade 3-5
(87% vs 72%) adverse reactions [see Clinical Studies (14)]. NCI-CTC grade 3-4 adverse reactions
occurring at a higher rate in Vectibix-treated patients included rash/dermatitis acneiform (26% vs
1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea,
hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).
NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix-treated patients (7%
vs 4%) and included fatal events in three (< 1%) Vectibix-treated patients.
As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab, and
chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent

69924-R1-V1
(oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study,
compared with those randomized to bevacizumab and chemotherapy.
In a single-arm study of 19 patients receiving Vectibix in combination with IFL, the incidence of NCI-
CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in one patient. In a singlearm
study of 24 patients receiving Vectibix plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea
was 25%.
Severe diarrhea and dehydration, which may lead to acute renal failure and other complications,
have been observed in patients treated with Vectibix in combination with chemotherapy.
Vectibix is indicated as a single agent for the treatment of epidermal growth factor receptor (EGFR)-expressing,
metastatic colorectal carcinoma (mCRC) with 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 improvement of progression-free
survival. Currently, no data demonstrate an improvement in disease-related symptoms or increased survival with
Vectibix.
These are not the only risks associated with the use of Vectibix. Please see the enclosed full prescribing
information for more information about the risks associated with the use of this product. This information is also
available at www.vectibix.com.
Should you have any questions, require further information on product safety, or wish to report adverse patient
experiences, please contact Amgen’s Medical Information Connection at 1-800-77-AMGEN.
Alternatively, adverse events may be reported to FDA’s MedWatch reporting system:
� by phone (1-800-FDA-1088), by facsimile (1-800-FDA-0178),
� online (https://www.accessdata.fda.gov/scripts/medwatch/), or
� by mail using the MedWatch Form FDA 3500 postage paid form, to the FDA Medical Products
Reporting Program, 5600 Fishers Lane, Rockville, MD 20852-9787.
Sincerely,
Michael E. Severino, MD
Senior Vice President, Global Development and Chief Medical Officer
Amgen