Presurgical test predicts breast cancer response to erlotinib

March 13, 2008

NEW YORK (Reuters Health) - A short-term presurgical trial of erlotinib (Tarceva) in patients with stage 1 to IIIA breast cancer may predict which patients will respond to erlotinib treatment after tumor resection.

In a multicenter study report in the February 20th issue of the Journal of Clinical Oncology, investigators found that estrogen receptor (ER)-positive cancers responded to this presurgical testing, but other breast cancers failed to respond to erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.

This strategy of identifying which cancer patients are good candidates for a certain treatment may speed a drug's approval process, the investigators add.

Dr. Marcia Guix of Vanderbilt University School of Medicine in Nashville, Tennessee, and colleagues administered erlotinib, 150 mg orally for 6-14 consecutive days until the day before surgery, to 41 patients with stage I-IIIA invasive breast cancer. Erlotinib plasma levels and drug-induced changes in tumor cell proliferation and apoptosis were assessed in pre- and post-surgical breast tissue.

The researchers found that "5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis...The inhibition of proliferation occurred in ER-positive but not in human epidermal growth factor receptor 2 (HER-2)-positive or triple-negative cancers."

The primary adverse effects of erlotinib therapy were diarrhea and rash, which were not severe.

Dr. Guix and associates write that "this pre-surgical study supports the feasibility of testing novel therapies during the pre-approval process to investigate a tumor profile of potential use in subsequent clinical studies that address drug efficacy."

"We speculate that this approach may expedite the drug development process by potentially informing the exclusion of non-responsive patients who will dilute the net signal of clinical activity of a drug or a combination. In the case of erlotinib, these patients would be those with HER-2-positive and the triple-negative cancers."

In an accompanying editorial, Dr. Tufia C. Haddad and Dr. Douglas Yee of the University of Minnesota Cancer Center in Minneapolis note that one of the main strengths of this study is that it used patients -- not mice -- to test tumor response to a new drug.

"The idea that EGFR inhibitors should be tested in triple-negative breast cancer is supported by the preclinical data, but not by this study," the editorialists comment. "The mice helped, but plans went awry, and they could not substitute for a well-designed clinical trial."

The investigators enrolled "all-comers," Drs. Haddad and Yee note. "By not pre-selecting patients, they provided important data necessary to design the next generation of erlotinib studies. Moreover, they showed how a small neoadjuvant study with built-in tissue acquisition could provide strategies to optimize erlotinib use in breast cancer."