Herceptin erases survival difference between HER2- patients

ABSTRACT: Use of trastuzumab levels the playing field for HER2-positive stage IV breast cancer patients, compared with HER2-negative patients.

CHICAGO-The addition of trastuzumab (Herceptin) to the arsenal of breast cancer agents has elevated the prognosis of HER2-positive patients to that of HER2-negative patients, according to an institutional review from M.D. Anderson Cancer Center.

The retrospective study included 2,091 women with stage IV or recurrent breast cancer who were diagnosed between 1991 and 2007. Patients were classified as having HER2-negative disease (85%), HER2-positive disease treated with first-line trastuzumab (9%), and HER2-positive disease without first-line trastuzumab (6%). At a median follow-up of 18 months, for the whole study population, median survival was nearly 29 months, 1-year survival was 76%, and 2-year survival was 55%.

Outcomes were best for HER2-positive patients receiving trastuzumab (see Table 1). In a multivariate analysis, HER2-positive patients receiving trastuzumab had a 44% reduction in risk of death, compared with HER2-positive patients not receiving trastuzumab (P < .0001). Compared with HER2-negative patients, HER2-positive patients receiving trastuzumab had absolute increases in survival of nearly 12% at 1 year and 8% at 2 years, she emphasized.

“The introduction of trastuzumab has altered the natural history of HER2-positive breast cancer,” said Shaheenah Dawood, MD, who presented the study at ASCO 2008 (abstract 1018).

Commenting to ONI, Clifford Hudis, MD, chief of breast cancer medicine at Memorial Sloan-Kettering Cancer Center, pointed out that CALGB9840 also found that HER2-positive patients receiving trastuzumab had outcomes as good as HER2-negative patients, and that adjuvant trastuzumab studies suggest the same. “The M.D. Anderson study is a large single-institution trial that is confirmatory,” he said.

Initial nonresponders may benefit

Investigators from the National Cancer Institute of Italy in Milan also found that giving trastuzumab in the metastatic setting greatly increases survival, including continuing it upon progression or re-starting it even in patients who initially lacked response (ASCO abstract 1062).

The observational Demetra Study of 440 consecutive metastatic patients from 22 Italian centers found a response rate of 55%, and overall survival of 34 months among patients receiving trastuzumab. For 272 patients who progressed during treatment, 57% continued trastuzumab while 43% discontinued it, which produced significant survival differences at 3 years (36.6% vs 14.8%, respectively). Trastuzumab in combination with taxanes offered the best outcomes, Sylvie Menard, MD, reported.

Initial nonresponders doubled their median survival time from 12 to 24 months, Dr. Menard said.

“If you respond first-line, you have an incredible improvement in survival. But even if you do not respond initially, there is benefit in continuing trastuzumab, indicating that resistance to trastuzumab may be an inappropriate concept as new biological drugs are considered,” she suggested.

Dr. Menard recently led a retrospective study that aimed to reevaluate the role of HER2 in 1,795 newly diagnosed breast carcinomas.

They found that HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, but HER2 2+ only in node positive. Dr. Menard’s group suggested that these tumors are distinct diseases with specific features and outcomes (Annals of Oncology online, June 9, 2008).