Yesterday researchers at the annual AACR meeting announced the results of a clinical trial of a new drug with activity in some forms of breast cancer. Palbociclib (PD-0332991), a pill developed by Pfizer, was tested in women with metastatic breast cancer cells with estrogen receptors and lacking Her2. These ER+/Her2- tumors represent the most common breast cancer subtype, which is one reason so many people are eying the results of this relatively small, randomized study.
The phase 2 trial, called PALOMA-1 included 165 post-menopausal women with advanced ER+/Her2 negative disease. The research subjects were assigned to take either Letrazole (Femara, an aromatase inhibitor, a drug that inhibits estrogen synthesis) alone, or Letrazole and also the experimental drug, Palbociclib. The study found a highly significant difference in progression free survival (PFS), the intended endpoint: the mean time until disease progressed was 20.2 months among women who took Palbociclib, as opposed to 10.2 months for those assigned to Letrazole alone. The p-value for the difference between the arms (1-sided) was 0.0004. That’s a powerful result.
But there was no statistically significant difference in overall survival between the two groups, a fact that was irksome to some observers, particularly in the biotech investment world, and to some who were reminded of the Avastin story and its fall-out. Most of the women lived for approximately 3 years after enrolling, with a trend of a few months favoring the Palbociclib arm. Another problem is that over half the patients were recruited to the study based on biomarker results, having to do with cyclin D1 amplification and/or loss of p16. So it could be the results are more relevant to breast cancer patients who have those particular changes. How those molecular features, enriched in the final study population, relate to Palbociclib’s usefulness in breast cancer and other tumor types warrants more evaluation, for sure.
My feeling is that this may prove to be a useful drug, not just in breast cancer. Any medication which interferes with cell growth by blocking cyclin-dependent kinases (enzymes) called CDK-4 and -6 could be useful in quite a few malignancies. The main side effect was suppression of the bone marrow (low blood cells). Some questions I’d like to ask the researchers, and which I hope they’ll address in the Phase III study, is if certain types of mets (e.g. lung vs. bone) or certain molecular subtypes are more tempered by this drug.
As for 10 months of PFS – if it pans out in a formal, published work, that’s valuable. Imagine that you’re 55 years old and living with metastatic breast cancer. A drug that is likely to delay, by most of 2 years, your tumor’s expansion into the lungs (causing shortness of breath), or bones (causing fractures and pain) or liver, and elsewhere can be worth a lot. It’s about the quality of life, whether or not it’s extended.
One final concern is that this study wasn’t blinded, so the doctors’ assessment of how the patients were doing, and the patients’ assessment of how they were feeling, may have been influenced by their knowing which arm they were on. Also, because this new drug is a pill, some insurance may not cover it – a policy issue that applies to many new cancer drugs.