- Women with a type of advanced breast cancer lived significantly longer when given Novartis' targeted therapy Kisqali in addition to standard hormone treatment, a first for a class of drugs that includes Pfizer's top-selling Ibrance and Eli Lilly's Verzenio.
- Three and a half years after beginning treatment, just over 70% of women who received Kisqali on top of hormone therapy were still alive compared to 46% of those given placebo instead of Novartis' drug, according to data presented Saturday at the annual meeting of the American Society of Clinical Oncology. Previous results had shown a benefit only on progression-free survival, or time until disease worsening or death.
- The Phase 3 study, called MONALEESA-7, focused on younger, pre- or perimenopausal women aged 18 to 59 whose cancers were hormone receptor positive but negative for a protein called HER2 that allows for treatment with drugs like Herceptin.
Breast cancer is highly treatable when detected early. For the estimated 250,000 women diagnosed with metastatic disease each year, however, five-year survival rates are low and little changed from two decades ago.
Standard treatment for hormone receptor positive tumors involves drugs that work by either blocking hormones like estrogen from fueling cancer growth, or by reducing hormone production altogether.
Recent years have seen the approval of targeted therapies designed to inhibit enzymes called cyclin-dependent 4/6 kinases, which are thought to promote cell cycle progression. Pfizer's Ibrance (palbociclib) was first, in early 2015, followed by Novartis' Kisqali (ribociclib) and Eli Lilly's Verzenio (abemaciclib).
Both Ibrance and Verzenio are OK'd for use with initial endocrine therapy in postmenopausal women only, while Kisqali is cleared for pre- and perimenopausal women as well. All three are aimed at HR+/HER2- advanced breast cancer.
Clinical trials have proved the drugs to be effective at lengthening progression-free survival but, until the MONALEESA-7 data disclosed Saturday, none had shown a survival benefit.
"I think it's a very high mark for us to actually cross this boundary and show [statistical] significance on this endpoint," said John Tsai, Novartis' chief medical officer, on a conference call with reporters before the ASCO meeting.
The study, results from which were also published in the New England Journal of Medicine Saturday, found patients on Kisqali and endocrine therapy were at a 29% lower risk of death than those on endocrine therapy alone — a benefit that began to emerge two years from initiation of treatment and widened through the study's stopping point of 42 months.
Treatment wasn't definitive, though. A roughly similar percentage of patients from each arm — 69% from the Kisqali group and 73% from the control group — went on to receive subsequent therapy.
Still, the clear improvement in survival will likely spur more doctors to consider Kisqali alongside initial endocrine therapy, especially given the lack of similar positive data supporting Verzenio and Ibrance.
"It's meaningful, at least for the population [studied], that we're seeing the survival advantage," said Debasish Tripathy, chair of the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, in an interview. Tripathy was a principal investigator in Novartis' study and has received funding from the company.
Still unanswered, though, is why MONALEESA-7 showed that advantage versus studies of its rival CDK 4/6 inhibitors, which didn't.
Novartis' Tsai credits the survival benefit to Kisqali's greater selectivity in binding to CDK4 rather than CDK6, but admitted the implications of such a difference aren't yet clear.
"The exact role of CDK4 versus CDK6 is unknown," he said. "We're generating some hypothesis and we're also looking at preclinical models to look at this in more detail."
Patient populations may also have played a role. Pfizer's PALOMA-3 study of Ibrance, for example, enrolled mostly postmenopausal women who were more heavily pretreated versus those in MONALEESA-7. Breast cancer is also thought to be more aggressive in premenopausal women.
"These differences may limit the applicability of cross-trial comparisons," the authors of the NEJM paper wrote.
For now, though, Novartis will likely enjoy a needed boost. Prescription data show Ibrance to hold a wide lead over both Kisqali and Verzenio, and Pfizer's first quarter sales of $1.1 billion for the drug tower over the the $91 million and $110 million earned by Novartis and Lilly, respectively, during the same period.
Kisqali's results also lift the Swiss pharma's efforts in breast cancer research. Just over a week ago the Food and Drug Administration approved Novartis' Piqray (alpelisib) for HR+/HER2- advanced breast cancer with a specific mutation known as PI3KCA, making it the first such drug ever cleared for use in the U.S.
Novartis forecasts both drugs to eventually earn more than $1 billion in peak annual sales. The company expects it will take time for physicians to adopt testing for PI3KCA and envisions the drugs could be used before or after each other.