Patients being treated for the first time with chemotherapy and Avastin® (bevacizumab) do worse if Vectibix™ (panitumumab) is added to their chemotherapy. Median time until the cancer progresses is shorter, and they have more serious side effects.
KRAS status made no difference. Both patients with wild-type and mutated KRAS in their tumors had worse outcomes when panitumumab was part of their treatment.
The research team recommends that Vectibix not be added to chemotherapy with Avastin to treat colorectal cancer that has spread.
The Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) trial was stopped early when monitors reviewing data from the clinical trial found that both progression-free survival and survival were better in the standard chemotherapy arm that did not include Vectibix. Previously, an interim safety analysis had shown more serious side effects with Vectibix.
Over 1,000 patients were originally enrolled in the trial, 823 on an oxaliplatin regimen and and 230 receiving irinotecan. All patients got Avastin, and half were randomly assigned to get Vectibix as well. The primary goal of the trial to to find out if adding Vectibix to chemotherapy and Avastin increased time before cancer got worse (progression-free survival).
Study results in May of 2007 showed:
- Median progression free survival time in the control chemotherapy and Avastin arm was 11.4 months compared to 10.0 months in the experimental arm that added Vectibix.
- Response rates (tumor shrinkage) between the two groups were not significantly different: 46 percent for patients who got experimental oxaliplatin chemo, Avastin, and Vectibix versus 48 percent for the oxaliplatin control group. For the irinotecan chemotherapy regimen, response was 43 percent for the experimental and 40 percent for the control arms.
- Median overall survival time for the oxaliplatin chemotherapy control was 24.5 months compared to 19.4 months when Vectibix was added. In the irinotecan chemo group, overall survival time was 20.5 months for the control arm without Vectibix and 20.7 months when Vectibix was added.
As would be expected there was more skin rash and severe skin rash among patients who received Vectibix. However, they also had more diarrhea, dehydration, increased magnesium levels, and blood clots in their lungs and deep leg veins. About 1 in every 5 patients had at least one serious side effect in the Vectibix arm. More patients in the Vectibix arm needed dose reductions and treatment delays than those in the control group.
About 40 percent of all patients had KRAS mutations in their tumor tissue. However, that made no difference in progression-free survival.
Reporting results in the Journal of Clinical Oncology, J. Randolph Hecht, M.D., and his colleagues wrote,
In conclusion, our results do not support the use of panitumumab in combination with bevacizumab and oxaliplatin- or irinotecan-based chemotherapy for the treatment of metastatic colorectal cancer. Administration
of chemotherapy and dual EGFR/VEGF inhibition should be conducted only in a research setting, using selected populations and/or novel administration schedules or combinations. Molecular markers in this setting should expand beyond the KRAS biomarker.
SOURCE: Hecht et al., Journal of Clinical Oncology.Early Release ahead of print, December 28, 2008.