The updated statistics from the American Cancer Society show that the overall cancer death rate has declined continuously in the United States from 1991 to 2016 by a total of 27%. The 2019 estimates predict 217,270 new breast cancer cases in the US and 42,260 deaths. The overall mortality rate is improving for colon, lung, and breast cancer. This is great news for our patients!
Her2-positive breast cancer is a great example of how scientific discovery can translate into lives saved. We routinely test for expression of the Estrogen, Progesterone, and Her2 receptor on the surface of breast cancer cells. In the case of Estrogen or Progesterone Receptor positive breast cancer, blocking activation of the receptor with drugs such as Tamoxifen or the aromatase inhibitors lead to the death of the cancer cells and improvement in outcomes for patients. In the same way, blocking of the Her-2 receptor in cases where this receptor is over-expressed (20% of the breast cancer cases), leads to cancer cell death in the lab and improved outcomes in the clinic.
The sequence of approvals for drugs that block the Her2 pathway in breast cancer has been impressive and life-saving. I will first discuss the timeline of anti-Her2 drug approvals in the setting of locally advanced, non-metastatic breast cancer.
Locally advanced disease
2006 Herceptin (trastuzumab)
The first anti-Her2 monoclonal antibody used in patients, was added to chemotherapy regimens given after surgery. The 10-year survival rate improved significantly from 78% to 85% as seen in the BCIRG 006 study.
2013 Perjeta (pertuzumab)
An anti-Her2 monoclonal antibody that binds to the Her2 receptor in a different location. The addition of the Perjeta to Herceptin containing chemotherapy regimens led to further improvement in outcomes for high-risk patients.
2017 Nerlynx (neratinib)
is an oral inhibitor of Her2. Nerlynx is started after the completion of Herceptin and given for one year. Studies showed 94.2% of women who took Nerlynx were free of cancer recurrence or death, as compared to 91.9% of those who were not.
2019 Kadcyla (ado-trastuzumab emtansine)
the first monoclonal antibody against Her2 linked to a chemotherapy drug (emtansine). This drug allows for the delivery of the chemotherapy agent directly into Her2-positive cells. In 2019, Kadcyla was approved to for patients treated with anti-Her2 therapy, chemotherapy and surgery but were found to have residual tumor remaining in their surgical specimen.
As you can see, the additive effect of these drugs given together or in sequence, given before and/or after surgery, has dramatically improved the cure rates, over 90% in some studies.
What about metastatic disease?
While we cannot cure metastatic Her2-positive breast cancer, the addition of these new anti-Her2 drugs can improve survival. In a study updated in 2015, the addition of Perjeta and Herceptin to chemotherapy improved overall survival by an amazing 16 months! Just think of how important that extra time is for patients and their families.
A 2015 study showed that the addition of Perjeta to chemotherapy and Herceptin in metastatic cancer patients resulted in an extra cost of $472,688 per quality-adjusted life-years gained. The study concluded that Perjeta should be classified as not cost-effective, despite adding 16 months of survival?? The rationing of drugs based on cost is routinely done in countries with socialized medicine and several studies have shown that survival rates are lower in those countries. In the US, we should (and are) moving toward free-market solutions to reduce costs. Examples include replacing consolidated health systems with physician-owned practices and increasing the approval of biosimilars to provide competition for the more expensive biologic drugs such as Herceptin and Perjeta. Free market competition is improving the quality and cost of health care in Charlotte and across the country and, as physicians, we must act to prevent rationing, socialization, and corporate control of health care.