If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  KRAS Status Influences Outcomes in Metastatic Colorectal Cancer Treated With Panitumumab: Presented at ASCO-GI 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]
|
