New Standard of Care
The original studies of trastuzumab showed improved OS in late-stage (metastatic) breast cancer from 20.3 to 25.1 months, and in early-stage breast cancer, it reduced the risk of cancer returning after surgery by an absolute risk of 9.5% and the risk of death by an absolute risk of 3%.
New therapies directed at HER2 are being developed, among them pertuzumab, a humanized monoclonal antibody that binds HER2 at a different epitope of the HER2 extracellular domain (subdomain 2) than that at which trastuzumab binds. Pertuzumab prevents HER2 from dimerizing with other ligand-activated HER receptors, most notably HER3. Like trastuzumab, pertuzumab stimulates antibody-dependent, cell-mediated cytotoxicity. Because pertuzumab and trastuzumab bind to different HER2 epitopes and have complementary mechanisms of action, these 2 agents, when given together, provide a more comprehensive blockade of HER2 signaling and result in greater antitumor activity than does either agent alone in HER2-positive tumor models. 12 In phase 2 studies, a pertuzumab–trastuzumab regimen has shown activity in patients with HER2-positive metastatic breast cancer and in patients with early breast cancer. 13
In the phase 3 CLEOPATRA study, the combination of pertuzumab plus trastuzumab plus docetaxel, used as first-line treatment for HER2-positive metastatic breast cancer compared with placebo plus trastuzumab plus docetaxel, significantly prolonged PFS (18.5 months vs 12.4 months), with no increase in cardiac toxic effects. 12 In a recent updated follow-up of the CLEOPATRA study, the addition of pertuzumab to trastuzumab and docetaxel showed a significantly better median OS (56.5 months vs 40.8 months; hazard ratio, 0.68; P < .001). 14 From these results, this combination regimen is now considered a first-line therapy for patients with HER2-positive metastatic breast cancer.
However, the cost of cancer treatment has become a mounting concern during the past decade, as new therapies come down the pipeline with ever-increasing price tags. Trastuzumab costs about $4,500 a month, and the newer pertuzumab runs about 30% higher, at $6,000 a month. For a full course of treatment, the cost of the pertuzumab and trastuzumab combination could go as high as $195,000, depending on the duration of therapy and the choice of taxanes.
Conclusions
The landscape of therapeutic options in high-risk, young patients with early-stage breast cancer as well as patients with advanced or metastatic disease is changing rapidly.
Clinicians now have 2 new first-line options for the treatment of advanced hormone receptor-positive, HER2-negative breast cancer. A phase 3 trial demonstrated that fulvestrant monotherapy offers improved PFS and some improvement in OS compared with anastrazole in postmenopausal women. A phase 2 trial showed that palbociclib plus letrozole offers improved PFS in postmenopausal women. Based on the SOFT and TEXT trials, clinicians treating high-risk premenopausal women now have some data to inform the debate about whether ovarian suppression should be added to hormone therapy.
Based on the CLEOPATRA trial, clinicians can now consider combination pertuzumab and trastuzumab and docetaxel as first-line therapy for patients with HER2-positive metastatic breast cancer.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
