Drug Topics - March 10, 2008 - (Page HSE6) 6 HSE DRUG TOPICS MARCH 10, 2008 www.drugtopics.com Clinical Practice Genetic makeup predicts colorectal cancer response to panitumumab Naomi Pfeiffer mgen announced the results of a dramatic new biomarker analysis indicating that in metastatic colorectal cancer (mCRC) patients who have failed all other chemotherapy regimens, the efficacy of panitumumab (Vectibix) is confined to those with nonmutated (wild-type) KRAS gene tumors. In such patients, Vectibix significantly increases progression-free survival (PFS) and impacts quality of life for the better. The new data—reported by lead author Rafael Amado, M.D., an Amgen scientist, in an oral session at the recent 2008 Gastrointestinal Cancers Symposium in Orlando – were generated from an analysis of an earlier Phase III randomized, controlled clinical trial that first defined the treatment effect of panitumumab in patients with metastatic colorectal cancer (mCRC). In September 2006, findings from that pivotal trial (“408”) led the Food & Drug Administration to approve panitumumab later that year as second- or thirdline therapy for RC in patients who did not respond to standard chemotherapy and had exhausted all other treatment options. The FDA commented: “The effectiveness of Vectibix for this indication is based entirely on progression-free survival. Currently, no data are available showing that Vectibix can also bring about an improvement in disease-related symptoms or increased survival.” Interestingly, in 2006 the corresponding European regulatory body—the European Committee for Medicinal Products for Human Use (CHMP)—did not approve the drug at first. It was only during several heated sessions later that CHMP members changed their minds and conditionally approved panitumumab in the European Union for patients with refractory mCRC— A but only those patients whose tumors lack a KRAS mutation. Similar marketing applications have been filed with Health Canada, Australia, and Switzerland. “Our study yet again confirms that patients with advanced colorectal cancer will benefit from Vectibix, but only if they are among the 60% with a normal form [wild-type] of the KRAS gene present in their tumors— not a mutation,” emphasized Amado. “KRAS gene mutations occur in some 40% of advanced colorectal cancer patients,” he said. From the clinical perspective, Amado had a positive outlook: “By testing for KRAS mutations, physicians may now be able to identify which patients will most likely benefit from panitumumab treatment and potentially avoid the unnecessary side effects and expense in those who are unlikely to respond…Understanding cancer mutation status can help identify optimal drug therapy for a patient.” No effect of Vectibix therapy was observed in patients who had tumors with KRAS mutations, he added. “The mutated KRAS gene is clearly associated with drug resistance.” The pivotal Phase III study on which the current analysis was based involved 427 patients whose KRAS status was known; 43% of them had a mutated KRAS gene. All the patients had metastatic colorectal cancer and had experienced the entire range of standard treatment options to no avail. They were now randomized to receive either best supportive care (palliative care with no anti-cancer drugs) or best supportive care plus panitumumab every two weeks. For the latter group, median progression-free survival was 12.3 weeks for those with a normal KRAS gene versus 7.4 weeks for those with a mutated gene. For the http://www.drugtopics.com
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.