Source: DGNews  |  Posted 2 years ago

By Ed Susman

ORLANDO, Fla -- January 25, 2010 -- Formation of antibodies to the targeted
therapy panitumumab occur rarely among patients being treated for metastatic
colorectal cancer but even when these antibodies do appear they did not seem to
affect outcomes, researchers said here at the 2010 Gastrointestinal Cancers
Symposium (ASCO-GI).

Researchers combined data from 2 phase 3 studies on panitumumab and found that
the development of new neutralising antibodies occurred in 18 of 971 patients.

“Since panitumumab is a fully-human compound, we really didn’t expect to see a
lot of neutralising antibodies,” said Marta Starcevic, PhD, Amgen, Thousand
Oaks, California, on January 24. “And we were unable to see that the formation
of these antibodies has any impact on outcomes.”

One of the studies examined the use of second-line panitumumab 6 mg/kg plus
FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) compared with FOLFIRI
alone every 2 weeks until disease progression occurred or the patient developed
intolerability to the treatment. The second study compared panitumumab 6 mg/kg
plus FOLFOX4 (oxaliplatin, leucovorin, and 5-fluorouracil) with FOLFOX4 alone.
Both studies were randomised, multicentre, phase 3 trials of patients with
metastatic colorectal cancer.

Depending on the type of test for measuring antibodies that was used, or
whether the patients’ tumours expressed mutated or wild-type genetic factors,
new neutralising antibodies were identified in 4 of 501 patients treated with
panitumumab in the FOLFIRI trial and in 14 of 470 patients treated with
panitumumab in the FOLFOX4 trial.

“The incidence of anti-panitumumab antibodies was similar in patients with
tumours expressing wild type of mutant KRAS,” said Dr. Starcevic. “No evidence
of an altered safety profile was found in patients who tested positive for
anti-panitumumab antibodies.”

She did note, however, that a full analysis of whether the neutralising
antibodies impacted efficacy was difficulty to perform because so few of the
patients developed those antibodies.

The researchers performed the antibody analyses using serum samples from the
patients enrolled in the studies.

Funding for this study was provided by Amgen.

The 2010 Gastrointestinal Cancers Symposium is sponsored by the American
Gastroenterological Association Institute, the American Society of Clinical
Oncology, the American Society for Therapeutic Radiation Oncology, and the
Society of Surgical Oncology.

[Presentation title: Panitumumab Immunogenicity in Two Phase III Trials of
Patients With Metastatic Colorectal Cancer (mCRC) Treated With Panitumumab Plus
FOLFIRI or FOLFOX4. Abstract 433]