Vectibix in combination – pro

Panitumumab (Vectibix, Amgen) was approved by the FDA for the treatment of patients with EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, or irinotecan-containing regimens. The NCCN Colon Cancer panel added panitumumab as alternate option to cetuximab after first or second progression on previous therapy. This addition came with a recommendation that patients should not be excluded from therapy on the basis of EGFR results.

Vectbix is FDA approved as a single agent. It is experimental in combination. I briefly review the combination Vectbix and chemotherapy studies presented in ASCO GI 2008.

The first is an 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.


   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.
   181 Study
   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.
In conclusion, this is an investigational treatment still in an ongoing study.

 

NCCN.ORG, colon cancer, p.24

Wainberg Z, Hecht JR Panitumumab in colon cancer: a review and summary of ongoing trials. Expert opinion on biological therapy. 2006 Nov;6(11):1229-35.

Saif MW, Cohenuram M Role of panitumumab in the management of metastatic colorectal cancer. Clinical Colorectal Cancer 2006 Jul;6(2):118-24

Gibson TB, Ranganathan A, Grothey A Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clinical colorectal cancer 2006 May;6(1):29-31.

Tyagi P Recent results and ongoing trials with panitumumab (ABX-EGF), a fully human anti-epidermal growth factor receptor antibody, in metastatic colorectal cancer Clinical colorectal cancer 2005 May;5(1):21-3.

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