Colorectal cancer patients with a KRAS mutation in their tumors benefit when Avastin® (bevacizumab) is added to chemotherapy, as do patients with no mutation or wild-type KRAS.
Both the time until cancer got worse (progression-free survival) and time patients lived after beginning treatment (survival) were better when Avastin was added to chemotherapy regardless of tumor KRAS mutation. Avastin did not improve overall response rates in the patients with KRAS mutations.
However, overall prognosis is worse for patients with KRAS mutations than those with wild-type KRAS with either chemotherapy alone or chemotherapy with Avastin. As a group, they tend to live for a shorter time and have their tumors progress more quickly.
Results of an analysis of 280 tumor samples from an earlier Phase III trial comparing chemotherapy with Camptosar® (irinotecan), 5FU, and leucovorin to the same chemotherapy plus Avastin were presented at the World Congress on Gastrointestinal Cancer in Barcelona in June, 2008.
The original study (AVF-2107) randomly assigned a bolus chemotherapy regimen of irinotecan, 5FU, and leucovorin (IFL) or IFL plus Avastin for the initial treatment of metastatic colorectal cancer. Results showed that adding Avastin improved response, progression-free survival, and survival.
To discover whether a mutation in the tumor KRAS gene made a difference in how Avastin helped patients, researchers performed a DNA sequence analysis on 280 available tumors. Originally, 812 patients were enrolled in the trial, but the smaller group was very similar. Test results were correlated with overall survival, progression-free survival, and response rates.
- Original study group: 6.2 months for IFL alone, 10.0 months with Avastin
- Wild-type KRAS: 7.4 months for IFL, 13.5 months with Avastin
- Mutant KRAS: 5.5 months for IFL, 9.3 months with Avastin
- Original study group: 15.6 months for IFL, 20.3 months with Avastin
- Wild-type KRAS: 17.6 months for IFL, 27.7 months with Avastin
- Mutant KRAS: 13.5 months for IFL, 19.9 months with Avastin
Response to treatment (combination of complete and partial responses)
- Overall study group: 38.6 percent for IFL alone, 54.3 percent with added Avastin
- Wild-type KRAS: 37.3 percent versus 60.0 percent
- Mutant KRAS: 41.2 percent versus 43.2 percent
Although both patients with wild-type KRAS and mutated KRAS benefited from adding Avastin to chemotherapy, both progression-free survival and survival was better for wild-type KRAS patients, with chemotherapy alone and with chemotherapy plus Avastin. Avastin didn’t appear to add to the percentage of patients with mutated KRAS who responded to treatment.
In a news release from Barcelona, Dr. Herbert Hurwitz, Duke University in Durham, North Carolina, and principal investigator of AVF2107 said,
These data demonstrate that the addition of Avastin to standard chemotherapy is active for patients with metastatic colorectal cancer with both K-ras wild type and mutant tumors. The high response rate, PFS, and OS in the K-Ras wild type group are impressive and confirm that Avastin should be part of the first line management of patients irrespective of K-Ras status. On a practical level, K-ras testing is not needed to initiate treatment with Avastin.
SOURCE: Hurwitz et al., Clinical Benefit of Bevacizumab in Metastatic Colorectal Cancer is Independent of K-ras Mutation Status, Poster 35, World Congress on GI Cancer, June 2008.
Disclosure: C3 has accepted funding for projects and educational programs from Genentech, the manufacturers of Avastin, in the form of unrestricted educational grants. C3 has ultimate authority over website content.