FROM 2008 ORLANDO GI SYMPOSIUM
Not all patients treated with Vectibix® (panitumumab) will respond to it. In a randomized clinical that compared colorectal cancer treatment with Vectibix alone to the best supportive cancer care, only about ten percent had tumors shrink. All patients in the study had previously gotten worse on standard treatments. In this trial, Vectibix was given alone or as monotherapy.
In an attempt to figure out which patients were most likely to benefit from Vectibix, researchers measured tumor DNA for a mutation in the KRAS gene. They studied the differences in both treatment outcomes and patient-reported cancer symptoms and quality of life between those patients with mutated KRAS genes and those with normal or wild type KRAS.
About 43 percent of patients had a mutation in the KRAS gene.
Comparing patients with mutated KRAS with wild type KRAS, they found:
Impact on progression-free survival
- Wild type KRAS: Median time before cancer began to progress for patients on Vectibix was 12.3 weeks compared to 7.3 weeks for best supportive care.
- Mutated KRAS: Median progression-free survival was not different between the two groups (7.4 weeks for those on Vectibix and 7.3 weeks for those receiving supportive care.)
Impact on response to treatment
- All patients: 10 percent in group that received Vectibix had tumors shrink somewhat (partial response) compared to no partial responses in the best supportive care arm.
- Wild type KRAS: 17 percent partial responses with Vectibix compared to none in supportive care.
- Mutant KRAS: No partial responses in either the Vectibix group or the group that received best supportive care.
Impact on stable disease
- All patients: 25 percent had their cancer remain stable during the trial while on Vectibix compared to 10 percent on supportive care.
- Wild type KRAS: 34 percent had stable disease on Vectibix compared to 10 percent on best supportive care.
- Mutant KRAS: 12 percent had stable disease on Vectibix compared to 8 percent not receiving the drug.
Impact on quality of life
- Wild type KRAS: Scores of patient-reported outcomes on quality of life were better for patients receiving Vectibix and their cancer symptoms improved somewhat during treatment.
- Mutant KRAS: There was no difference in quality of life between the two groups and cancer symptoms and quality of life got worse during treatment.
Overall, the researchers felt that there was no benefit to treating patients with mutated KRAS with Vectibix in this particular setting — when they had gotten worse on all previous standard treatments and when Vectibix was used alone.
There is other research underway to study response to Vectibix earlier in metastatic colorectal cancer treatment and in combination with chemotherapy including the impact of KRAS mutations on that response.
Vectibix is approved by the FDA to treat patients with colon or rectal cancer who had progressed on all other therapies.
R.G. Amado, MD and colleagues concluded in a 2008 GI Symposium abstract that
Panitimumab efficacy in CRC is confined to patients with tumors lacking KRAS mutations. Wild type KRAS patient receiving panitumumab had better colorectal cancer symptoms vs best supportive care patients.
In his presentation, Dr. Amado also pointed out:
KRAS genotyping of tumors should be strongly considered in patients with metastatic colorectal cancer being treated with panitumumab monotherapy.
Disclosure: Fight Colorectal Cancer has accepted funding for projects and educational programs from Amgen in the form of unrestricted educational grants. Fight CRC has ultimate authority over website content.