New results presented today at the American Society of Clinical Oncology annual Meeting in Chicago have shown that the addition of a drug called a cyclin inhibitor significantly increases the chance of survival for younger women with a particular type of aggressive breast cancer.
The international clinical trial, called MONALEESA-7, involved 672 women under the age of 59, who had a specific type of breast cancer called hormone receptor positive/HER2 negative. All of the women were given endocrine therapies to suppress estrogen, with some of the women then randomized on the trial to be given the new drug ribociclib, with the others given a placebo.
After 42 months, 70% of women who took the combination therapy with ribociclib were still alive, compared with just 46% of women who received the endocrine therapy only, a 29% reduced risk of death over the duration of the trial for the women taking the new drug.
“This is the first study to show improved survival for any targeted therapy when used with endocrine therapy as a first-line treatment for advanced breast cancer,” said lead study author Sara A. Hurvitz, MD, Director of the Breast Cancer Clinical Research Program at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.
Although advanced breast cancer is less common in younger women than older woman, it appears to be becoming more common. In the U.S., in women aged 20 to 39, the incidence has been rising by 2% each yearbetween 1978 and 2008. In women under 59, it is the leading cause of cancer death.
“There’s a clear difference in favor of adding this new drug to the regimen. The study confirms the value of the treatment approach in these younger women who have this aggressive type of breast cancer,” said J. Leonard Lichtenfeld, M.D., acting chief medical and scientific officer for the American Cancer Society.
Although extending survival for women with these often-incurable advanced breast cancers is certainly a big step, currently the use of cyclin inhibitors in cancer treatment is often not considered to be ‘curative,’ rather they are life-extending and often come with less harsh side-effects than many conventional chemotherapies.
“Increased survival is important, but the unfortunate reality in metastatic breast cancer, is that its unusual to ‘cure’ women with advanced breast cancer with any of our current therapies. But, the history of cancer treatment has generally been modest, incremental steps over time in contrast to blockbuster breakthroughs,” said Lichtenfeld.
Ribociclib, marketed by Novartis as Kisqali, is one of three FDA-approved cyclin inhibitors,which block proteins which control cell division. The first of these, palbociclib (Pfizer’s Ibrance), was approved by the FDA in 2015 and is currently authorized for use in several different cancer types, with $4.1 billion in sales in 2018, with ribociclib lagging behind with a meager $235 million.
Palbociclib has already been tested in a similar trial in younger women with advanced breast cancer, but didn’t show the same increases in overall survival as the recent research with ribociclib.
“Why haven’t we seen the same significant change in survival with other cyclin inhibitors? If you look at this study carefully, you’ll see that the authors did address this and declare that its not exactly the same patient population. The women treated in the other trial with palbociclib may have had more advanced disease and have had other treatments beforehand,” said Lichtenfeld.
It remains to be seen whether one of these drugs is indeed more effective in this patient population or whether differences between the patients in the two trial account for the differing results.
“The jury is still out. The only way to properly do this is to do a head to head trial on the exact same patients to see whether there are any differences, but I’m unsure whether this will happen. Its not appropriate to draw comparisons between these two drugs based on this new trial,” said Lichtenfeld.