Source: DGNews  |  Posted 2 years ago

By Ed Susman

ORLANDO, Fla -- January 25, 2010 -- The addition of panitumumab to standard
colorectal cancer chemotherapy can benefit some patients but can be detrimental
to others who have a KRAS gene mutation, according to a phase 3 study presented
here at the 2010 Gastrointestinal Cancers Symposium (ASCO-GI).

“In patients who have a wild-type KRAS gene, the addition of panitumumab
results in a 1.8 month advantage in progression-free survival, but if the
patients’ tumours express a mutated form of KRAS, the use of panitumumab is
associated with 1.6 month worse outcome in progression-free survival,” said
Salvatore Siena, MD, Ospedale Niguarda Ca’ Granda, Milano, Italy.

For the study, Dr. Siena and colleagues enrolled 1,183 patients. They assigned
593 patients to receive panitumumab 6 mg/kg every 2 weeks plus the standard
colorectal cancer FOLFOX4 regimen of oxaliplatin, leucovorin, and
5-fluorouracil (5-FU) and assigned 590 patients to receive just FOLFOX4. KRAS
testing was completed in more than 90% of the patients in the study.

Dr. Siena noted that, previously, relationships between KRAS mutation status
and outcomes were based on retrospective analyses that often included less than
50% of the subjects in the trial. “Here we had KRAS mutation status available
in 93% of the patients who received panitumumab and 92% of the patients who
just received FOLFOX4,” he said at his poster presentation on January 24.

When panitumumab was added to FOLFOX4 patients whose tumours expressed
wild-type KRAS achieved a median 9.6 months of progression-free survival
compared with 8.0 months for patients receiving just FOLFOX4 (P =
.02), Dr. Siena said. “That was the primary endpoint in the trial.”

Patients who received panitumumab and had wild-type KRAS genes also experienced
a longer overall survival, a median of 23.9 months compared with 19.7 months
for those patients who were on FOLFOX4 alone (P = .07).

Dr. Siena suggested that the failure to meet statistical significance in
overall survival, a secondary endpoint, was due to dilution of the impact
because patients were switched to other agents. He said 20% of patients had
cetuximab added to their therapy after they progressed.

Similarly, response rates were higher with panitumumab in KRAS wild-type
patients compared with FOLFOX4. About 55% of the panitumumab patients responded
compared with 48% of the FOLFOX4 patients, but the numerical difference did not
reach statistical significance, he said.

But he noted that when panitumumab was given to patients with mutated KRAS, the
addition of the drug was detrimental to patients. “For patients with mutated
KRAS tumours, median progression-free survival was 7.3
month for patients getting the combination treatment compared with 8.8 months
for patients receiving FOLFOX4 alone [P = .02],” Dr. Siena said.

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: Randomized Phase III Study of Panitumumab (pmab) With
FOLFOX4 Compared to FOLFOX4 Alone as First-Line Treatment (tx) for Metastatic
Colorectal Cancer (mCRC): PRIME trial. Abstract 283]