SAN FRANCISCO—Early results with a regimen of gemcitabine(Drug information on gemcitabine) (Gemzar), cisplatin(Drug information on cisplatin) (Platinol), and trastuzumab(Drug information on trastuzumab) (Herceptin) in advanced non-small-cell lung cancer (NSCLC) patients overex-pressing HER-2 are encouraging, according to a presentation at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 1307).
The current standard-of-care chemotherapeutic agents used in NSCLC are relatively similar in their ability to improve survival, quality of life, and symptom relief. "So if we can find a way to improve these by adding Herceptin in a practical manner, then patients will benefit," principal investigator Ralph G. Zinner, MD, assistant professor of medicine at M.D. Anderson Cancer Center, told ONI in an interview.
Co-investigator is Roy Herbst, MD, PhD, assistant professor of medicine and cancer biology.
The current phase II study addresses several issues, primarily efficacy vs historical controls. Dr. Zinner said that chemotherapy response rates in three phase III NSCLC trials of the cisplatin/gemcitabine combination have been around 35% (40.6%, 31%, and 40%). "We felt that achieving a 55% response rate by adding Herceptin would be good evidence of benefit," Dr. Zinner stated.
He noted, however, that use of historical controls who did not receive trastuzumab as part of their chemotherapy regimen is complicated by the absence of response data in patients identified as having HER-2 overexpression. This is important, he said, since HER-2 overexpression may predict either better or worse response to standard chemotherapy.
Assessment of HER-2 overexpression was another area of study interest. Dr. Zinner pointed out that fluorescence in situ hybridization (FISH) was not used because in NSCLC (unlike in breast cancer), DNA amplification is not the usual mechanism of overexpression. Through poorly understood mechanisms, within the subset of lung cancer tumor tissues that overexpress HER-2, only a small percentage have such DNA amplification detectable through FISH.
Immunohistochemistry (IHC), however, does detect the HER-2 protein gene product in lung cancer. Dr. Zinner said that preclinical studies have shown antibodies against HER-2 to have antipro-liferative effects even without DNA amplification.
