“Where do current findings leave us in terms of anti-HER2 therapy options?” asked Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Center, Boston, who moderated the Best of ASCO Boston meeting. New drugs are joining trastuzumab (Herceptin) and lapatinib (Tykerb), and there will be some juggling for position, though the FDA-indicated labeling is guiding their use at this point, he said.

New Options and Current Standards

In the first-line setting for metastatic disease, docetaxel/trastuzumab/pertuzumab (Perjeta) was recently approved (weekly paclitaxel can be used instead of docetaxel), but Dr. Burstein has economic concerns with this regimen. The estimated wholesale cost of pertuzumab is $5,900 a month; when paired with trastuzumab at $4,500 a month, this means that a typical 18-month course of treatment exceeds $187,000.

In the second-line and refractory settings, T-DM1 is expected to receive FDA approval. “Its side-effect profile and possible quality-of-life advantages will make it an appealing first-line option, but this will not be the labeled indication.”

In the third and subsequent lines, chemotherapy plus trastuzumab or lapatinib plus capecitabine (Xeloda) remain the standards. Trials are examining whether ongoing pertuzumab treatment might be clinically valuable here. At least one early-phase trial has examined the triplet of T-DM1, pertuzumab, and paclitaxel in heavily pretreated patients, which Dr. Burstein called “the most expensive treatment regimen in all of medical oncology.” While it appears reasonably well tolerated, with a response rate of about 40% it seems no better than single-agent T-DM1, he noted. 

Impact of ALLTO

In the neoadjuvant setting, dual HER2 inhibition with trastuzumab plus lapatinib yields the highest pathologic complete response rates but has not been adopted in clinical practice. For one thing, lapatinib has not been shown to alter the natural history of the disease, an issue that is being studied in the adjusted Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALLTO) trial.

Last fall, ALLTO discontinued the single-agent lapatinib arm due to lack of benefit, and is continuing to study single-agent trastuzumab, trastuzumab followed by lapatininb, and trastuzumab plus lapatinib. The results of ALLTO may change the way lapatinib will be used (or not used) moving forward, including its role in neoadjuvant treatment. Meanwhile, the next generation of neoadjuvant studies is being built around drugs other than lapatinib, he said. ■