In my 10 years as a breast cancer specialist, I have to say that hands-down the most significant progress we have seen in breast cancer therapy has occurred in women with Her2 positive disease, about 20% of the breast cancer population. In fact, a recent 10 year follow up study of one of the trials that led to trastuzumab’s (Herceptin) approval in 2005 demonstrated a near 10% improvement in overall survival (84% survival at 10 years compared to 75%) in those women receiving trastuzumab along with chemotherapy compared to women receiving chemotherapy alone. That’s a lot of lives saved in a 10-year period! These numbers will surely continue to improve with the wealth of new agents developed to overcome trastuzumab resistance in the Her2 positive patient population.
I am now pleased to say that the same progress is coming to other breast cancer subtypes, as scientists are beginning to understand the pathways of resistance to standard therapies, including the commonly used hormonal therapies (i.e. tamoxifen and aromatase inhibitors such as anastrozole, letrozole and exemestane). This resistance is felt to be one of the reasons that some women with hormone receptor positive breast cancer end up having their breast cancer come back as much as 5, 10, or even up to 20 years after their initial diagnosis.
One such triumph in overcoming endocrine resistance is the development of a drug called palbociclib (to be marketed as Ibrance). The FDA recently announced its approval of palbociclib for treating postmenopausal women with hormone receptor positive advanced breast cancer. The initial data, presented at the San Antonio Breast Symposium in December 2012, really knocked the socks off the breast cancer specialist medical community, including myself, as we have not seen such results since the advent of trastuzumab, detailed above. This data and subsequent follow up of the women on this trial, led to the approval of palbociclib in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive, advanced breast cancer (i.e. Stage IV, metastatic) as first-line endocrine-based therapy.
So, what do we know about palbociclib?
- Palbociclib is part of a class of drugs that inhibits cyclin-dependent kinases (CDKs) 4 and 6. These kinases help facilitate cancer cell growth. Inhibiting them slows growth.
- Palbociclib is taken orally.
- It seems to be very well tolerated, with the following being the most common side effects:
- Lowering of the white blood cells, without an increased rate of fevers or infections.
The Phase II study, PALOMA-1, which led to palbociclib’s FDA approval, included 165 women with hormone receptor positive, Her2 negative, advanced breast cancer. These women were randomized to receive either letrozole (an aromatase inhibitor) or letrozole + palbociclib as their first endocrine-based therapy at the time they were diagnosed with metastatic disease (Stage IV disease). The results showed that women receiving palbociclib along with letrozole on average lived 20.2 months without progression of their disease, compared to 10.2 months for women on letrozole alone. It essentially doubled the time to progression! This was such a significant finding that the FDA decided to grant palbociclib accelerated approval, meaning the drug is now available. However, continued confirmatory studies will determine if it remains available for this indication.
This promising study has led to the development of several larger (Phase III) studies in advanced breast cancer and in earlier stage breast cancer as well. In addition, palbociclib is just one of several drugs and classes of drugs in development to address the problem of endocrine therapy resistance.
So, what’s the downside? Well, as usual, everything comes with its price. The Associated Press reported on February 3, 2015 that Pfizer said it would price palbociclib at $9850 for a month-long course of drug, totaling over $118K per year. Pfizer was quick to mention that this price is not the cost that most patients or payors pay, after discounts to health plans are negotiated. While we know that there is a lot of money invested in the development of a blockbuster drug, some of these costs will need to be addressed as these new classes of drugs might become the new standard of care for women with early and late stage hormone receptor positive breast cancer in the next 5 years or so. That’s a huge percentage of the breast cancer population (about 2 out of 3), and, cumulatively, a huge financial commitment for the breast cancer community.
That being said, the progress that is being made in breast cancer, specifically in targeted therapies for breast cancer, is incredibly exciting. These targeted therapies are minimizing side effects and maximizing efficacy. Ultimately, this progress will result not only in improved longevity, but also an improved quality of life for our breast cancer survivors. Priceless.