By: Elaine Schattner
At the European Society for Medical Oncology (ESMO) Congress this week, investigators presented data for a new and potentially important drug, ribociclib (Novartis). This oral medication is clearly active in hormone receptor-positive (ER+ or PR+) breast cancer. The findings of the MONALEESA trial were published in the NEJM.
The main result is that for the most common form of advanced breast cancer, adding ribociclib to letrozole significantly improved progression-free survival (PFS), as compared to adding a placebo. After a year and a half (18 months) in this randomized, controlled clinical trial, PFS among women receiving ribociclib was 63.0%, vs. 42.2% in the placebo arm. That’s a big difference, when you consider that 99% of the patients on the study have stage 4, metastatic breast cancer.
One thing I like about the MONALEESA-2 trial is that the acronym stands for something: Mammary Oncology Assessment of LEE011’s Efficacy and Safety -2. LEE011 is an old name for ribociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6). The work was supported by Novartis.
Ribociclib is one of several CDK inhibitors being tried in breast cancer and other malignancies. In theory, it should be very similar to Pfizer’s Ibrance (palbociclib), about which I’ve written and which is already FDA-approved. Both ribociclib and palbociclib, along with Lilly’s investigational agent, abemaciclib, take aim at CDK-4 and -6, enzymes that may be overactive inside cancer cells.
My first question about Novartis’ new medication, ribociclib, is how it compares with palbociclib (Ibrance). Unfortunately, because these drugs have been evaluated in separate clinical trials, sponsored by independent pharmaceutical companies, by oncologists at distinct sets of medical centers, it’s hard to discern the differences.
Some facts emerge from the published MONALEESA-2 trial results. Ribociclib was more than a little (grade 3 or 4) toxic in 21% of patients, compared to 12% of those who got placebo, as reported. Among this drug’s common side effects are neutropenia (low white blood cells) and infection (often a consequence of low white blood cells). Neutropenia should be treatable, and to some extent is preventable, by prescribing filgrastim, a white cell growth factor that is available in generic form. Hair loss is frequent. Other problems with ribociclib are gut-related: diarrhea and nausea. Based on my discussions with patients who are taking these drugs, I know these side effects to be true. While diarrhea can be reduced by drugs like Imodium, it can be embarrassing, limiting out-of-home activities, and dehydrating, among other concerns. So we need patient-reported outcomes, and quality-of-life assessments.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.