Amgen announced interim results from two phase II studies of panitumumab, an investigational fully human monoclonal antibody that targets the epidermal growth factor receptor (EGFR). Results from both studies suggest that the antitumor activity of panitumumab was independent of tumor EGFR expression levels in patients with metastatic colorectal cancer who have failed standard chemotherapy. These data were presented at the 42nd annual meeting of the American Society of Clinical Oncology.

"EGFR staining is an immunohistochemical test to determine the amount of that protein on the surface of cancer cells and has been used to try to figure out who will respond to drugs targeting the receptor," said J. Randolph Hecht, MD, director of the UCLA gastrointestinal oncology program, clinical professor of medicine, UCLA David Geffen School of Medicine, Los Angeles, and the lead investigator of one of the studies. "These findings—that responses can be seen to anti-EGFR drugs regardless of tumor EGFR staining levels—show that this test does not identify which patients are most likely to benefit from these targeted treatments. Clearly, we need better ways to decide which patients should get these drugs."

Study Designs

The first study examined metastatic colorectal cancer patients with either low or negative (less than 1% positive cells) levels of tumor EGFR staining (the 250 study), while the second evaluated patients with the disease and tumor EGFR levels of at least 10% (the 167 study). Both ongoing multicenter, open-label, phase II trials are examining antitumor activity of panitumumab in patients with metastatic colorectal cancer who have failed standard chemotherapy, including oxaliplatin(Drug information on oxaliplatin) (Eloxatin) and irinotecan(Drug information on irinotecan) (Camptosar). Patients in both studies receive panitumumab at 6 mg/kg every 2 weeks until disease progression or drug intolerability.

Tumor assessments are conducted by an independent central radiologic review board from week 8 until disease progression. The primary study endpoint is objective response at week 16, which is subsequently confirmed. Secondary endpoints include objective response rate throughout the study, duration of response, progression-free survival, overall survival, and safety.

Interim Analysis

At the time of the interim analysis, the 250 study had enrolled 88 patients, with 23 evaluable for response. Thirteen percent (3/23) who received panitumumab monotherapy had a partial response, including two patients with tumor cells negative for EGFR staining. Stable disease was observed in 30% (7/23) of patients, for a total disease control rate (partial response plus stable disease) of 43%. The median progression-free survival time was 13.3 weeks. The study plans to enroll 150 patients.

Study 167 had enrolled 91 patients, and 39 were evaluable for response at the time of interim analysis. At week 16, 8% of patients (3/39) demonstrated a partial response, 21% (8/39) had stable disease, and 49% (19/39) had disease progression. The median progression-free survival time was 7.6 weeks. The study plans to enroll 300 patients.

The clinical trial protocols did not require premedication or a loading dose for administration of panitumumab, and the incidence of infusion reactions was low: 3% (3/88) grade 1 or 2 in the 250 study; 1% (1/88), and 1% (1/91) grade 3 (1 of which led to panitumumab discontinuation), in the 250 and 167 studies, respectively. There were no grade 4 or 5 infusion reactions. The most common reported adverse events associated with panitumumab were skin toxicities, fatigue, abdominal pain, nausea, and diarrhea. Grade 3 or 4 hypomagnesemia was observed in 8% (7/88) and 12% (11/91) of patients, respectively.