On February 3, 2015, the U.S. Food and Drug Administration (FDA) approved a new drug for the treatment of ER+ (Estrogen-Receptor positive) and HER2- (Human Epidermal Growth Factor Receptor 2 –negative) breast cancers. The drug, called Ibrance (palbociclib) was granted FDA approval through the agency’s accelerated approval program, based on promising results from a Phase II clinical trial. Results from the trial were published in January in the journal Lancet.
According to those results, 165 participants, all post-menopausal women with ER+ or HER2-, advanced metastatic cancers, were randomly split into two groups: a cohort of 81 patients was treated with Letrozole, a common drug used for hormonally-responsive breast cancers (including ER+ and HER2- cancers); 84 patients were given Letrozole plus Ibrance. None of these women had received other treatment.
For women receiving both drugs, their progression free survival was, on average, nearly twice as long as women who received Letrozole alone (20.2 months vs. 10.2). “Progression free survival” refers to the amount of time, post-treatment, someone has a disease without worsening symptoms. A Phase III trial is currently underway and will, hopefully, provide insight on any benefits for overall mortality.
Interpretations and Implications
Ibrance is the first drug of its kind on the market. Known as a “CDK inhibitor”, it targets specific proteins (cyclin- dependent kinases or “CDKs”) in cancer cells that are responsible for triggering different phases of cell division. Years of research have suggested that problems with this process can sometimes lead to tumor growth through unrestricted cell division, resulting in rapid cancer cell growth and multiplication. But Ibrance is the first drug to specifically target this.
In addition to the results about progression-free survival, other study results have shown that, for some women, Ibrance actually reduces the size of tumors. In general the results are positive, though some have expressed concern that the results may have been biased given the trial’s design: apparently, the investigators in this clinical trial were aware of which patients had been given Ibrance. Generally “blind studies” are considered the gold standard in epidemiology; if a researcher is “blinded” and does not know which patients have received a certain treatment, he or she cannot be biased (consciously or unconsciously) by that knowledge.
Despite these concerns, and despite the fact that the 165 participants seems like a small number for a clinical trial, it is likely that the FDA will give fast-tracked approval as few treatments are effective at prolonging life among women with advanced metastatic disease. For women with advanced disease, any prolonging of life free of disease is a welcome outcome. The response of the scientific community remains guarded, given the small number and concerns about trial design, but the Phase III trial will provide more evidence related to the drug’s effect, if any, on mortality.
Source: Finn SR et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. The Lancet 2015, 26: 25-35.
