Panitumumab, a new targeted treatment for advanced colorectal cancer, plus best supportive care extended progression-free survival (PFS) significantly, compared with best supportive care alone, Marc Peeters, MD, PhD, of Ghent University Hospital, Belgium, said at the 97th Annual Meeting of the American Association for Cancer Research (AACR) (abstract CP-1). FDA has granted the drug fast-track status, and it could be approved for use by the fall of this year.
WASHINGTONPanitumumab, a new targeted treatment for advanced colorectal cancer, plus best supportive care extended progression-free survival (PFS) significantly, compared with best supportive care alone, Marc Peeters, MD, PhD, of Ghent University Hospital, Belgium, said at the 97th Annual Meeting of the American Association for Cancer Research (AACR) (abstract CP-1). FDA has granted the drug fast-track status, and it could be approved for use by the fall of this year.
Panitumumab, which targets EGFR, is the third antibody treatment for advanced colorectal cancer to emerge in recent years. Bevacizumab (Avastin) targets VEGF and cetuximab (Erbitux) targets EGFR. Since panitumumab is a fully human monoclonal antibody, it may be less likely to provoke hypersensitivity reactions than cetuximab, which is a chimeric mouse/human antibody.
The randomized phase III trial included 463 patients with metastatic colorectal cancer who were positive for EGFR and whose tumors had progressed after at least two standard chemotherapy regimens. No prior antibody therapy was allowed. Patients were randomized to 6 mg/kg of panitumumab every 2 weeks plus best supportive care, which included steroids and pain medication (231 patients), or best supportive care alone (232 patients). Those receiving best supportive care could cross over to panitumumab treatment if their disease progressed.
With a medium follow-up of 19 weeks, the panitumumab patients had a 46% lower rate of disease progression or death, compared with best supportive care alone (P < .000000001). At 8 weeks, 49% of panitumumab patients had no disease progression vs 30% of the control group; at 24 weeks, the percentages were 18% vs 5%, and at 32 weeks, 10% vs 4%.
Tumor shrinkage was observed in 8% of the panitumumab patients (median duration, 17 weeks); there were no responses in the best supportive care group. Disease control (response rate plus stable disease rate) was 36% for panitumumab vs 10% for controls. The drug improved disease-free survival and disease control regardless of age, sex, performance status, primary tumor location, and EGFR status (1+, 2+, or 3+).
Overall survival did not differ between the two groups. However, most of the patients in the best supportive care group did begin taking panitumumab when their tumors progressed, and this may have confounded the ability of the trial to demonstrate an effect on overall survival, Dr. Peeters said. Of the 75% of control patients who crossed over to panitumumab, after a median follow-up of 7 weeks, 9% had a partial response and 32% had stable disease. One patient in this group had a complete response.
The drug was well tolerated. The most common side effect was skin rash, which occurred in more than 90% of patients. An exploratory analysis suggested that patients with more severe rash (grade 2-4 vs grade 1) had greater overall survival.
"The incidence of infusion reactions was low, with no grade 3-4 reactions," Dr. Peeters said. One patient discontinued treatment due to a grade 2 hyper-sensitivity reaction. Of 185 patients with post-baseline testing for antibody development, none tested positive for anti-panitumumab antibodies. Other toxicities were hypomagnesemia, fatigue, abdominal pain, nausea, and diarrhea.
Amgen has acquired Abgenix, providing Amgen with full ownership of the drug. The company has completed the biologics license application (BLA) for panitumumab and submitted it to FDA.
The next steps for panitumumab, Dr. Peeters said, include trials in combination with chemotherapy and other targeted agents and in first-line treatment of metastatic disease. Amgen is also looking at the drug in other cancers. Early trials are ongoing in EGFR-positive non-small-cell lung cancer (NSCLC) and head and neck cancers.