The ongoing ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trial, comparing adjuvant trastuzumab (Herceptin) with trastuzumab plus lapatinib, will offer important insight into the potential preventive value of lapatinib with respect to CNS relapse in early-stage HER2-positive disease, he wrote.
New Agents Also in Trials
Additional systemic and combination therapies representing a range of potential approaches are also under investigation, said Dr. Lin. These include the novel HER2-targeted therapies neratinib and afatinib, both of which are being evaluated in phase II trials, as well as cytotoxic agents targeting brain metastases specifically. The latter agents include the peptide-taxane conjugate GRN1005, the glutathione-pegylated liposomal doxorubicin 2B3-101, and the third-generation taxane TPI 287 – all three of which are being evaluated in phase I and II trials.
Also under investigation, she added, are PIK3CA inhibitors, mTOR (mammalian target of rapamycin) inhibitors, PARP (poly[ADP-ribose] polymerase) inhibitors, and VEGF (vascular endothelial growth factor)–targeting agents.
In order for research in this arena to bear fruit that translates into clinically effective strategies, the improvement of clinical trial availability and access should be a top priority, Dr. Lin stressed.
"Breast cancer patients with brain metastasis have been routinely excluded from clinical trials," which limits investigators’ ability to evaluate novel therapies, she said. "Our goal should be to increase and continue efforts to study novel agents in patients with brain metastases to establish better historical control data."
Dr. Lin disclosed financial relationships with GlaxoSmithKline, Genentech, Geron, Boehringer Ingelheim, Bayer, and Novartis.