Novartis’ breast cancer drug Kisqali already has two clinical wins under its belt showing a survival benefit over traditional treatment. Now, the company hopes a third, first-of-its-kind victory in newly diagnosed patients could give it a better shot at challenging Pfizer’s market-leading Ibrance.
In postmenopausal women with HR-positive, HER2-negative breast cancer with no prior systemic treatment for advanced disease, the addition of Kisqali to Novartis’ aromatase inhibitor Femara reduced the risk of death by 24%, Novartis unveiled at the European Society for Medical Oncology 2021 virtual congress.
Kisqali is now the first CDK4/6 inhibitor to demonstrate a statistically significant life extension benefit in the front-line treatment of this patient group. The phase 3 win is also important because Kisqali extended the time patients lived by over a year, the study's lead investigator, Gabriel Hortobagyi, M.D. of the MD Anderson Cancer Center, noted during an interview.
Patients who took Kisqali lived a median 63.9 months, compared with 51.4 months for those on Femara alone. At the six-year mark, 44.2% of Kisqali takers were still alive, versus 32% in the control group. Kisqali also pared down the risk for first next-line chemotherapy use by 26%.
Showing a statistically significant extension in survival for first-line breast cancer therapy is difficult, Hortobagyi explained in a statement, “because due to the development of resistance, patients receive four to 15 different types of treatment over the course of their disease and these dilute the effect of the first therapy.”
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The MONALEESA-2 trial at hand marks the third time a survival advantage has been reported for Kisqali in a late-stage study. The MONALEESA-3 trial returned a 28% reduction in the risk of death for the combination of Kisqali and AstraZeneca’s selective estrogen receptor degrader (SERD) Faslodex over solo Faslodex in a group of front- and second-line postmenopausal patients. The pairing of Kisqali and endocrine therapy demonstrated a 29% reduction of death in premenopausal women.
“It’s important to create the evidence for Kisqali’s benefit no matter which patient population, whether it’s first- or second-line setting, no matter which combination partner in terms of endocrine therapy; the data are very significant [and] set a new standard of care in metastatic breast cancer,” Myriam Mendila, head of medical at Novartis’ oncology department, said in a separate interview.
While MONALEESA-2 is the most important Kisqali readout to date, “putting the three MONALEESA studies together provides a very powerful image of what this particular CDK4/6 inhibitor can achieve,” Hortobagyi said.
But sales figures show a different story. Since the survival readout from MONALEESA-3 in the fall of 2019, Kisqali’s sales growth, especially in the U.S., didn’t really match the drug’s transformative nature the company has touted. In the second quarter, sales of Kisqali in the U.S. only came in at $83 million. While a recovery from a COVID-related slowdown in the first quarter, it wasn’t that different from the $79 million recorded for the same period in 2020.
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By comparison, Pfizer’s first-to-market CDK inhibitor Ibrance pulled in U.S. sales of $862 million in the second quarter. Though the number was down 7% year over year—which Pfizer blamed on more patient assistance program enrollees—the drug still maintained a huge lead, with 73% share, in first-line new patient starts.
Ibrance achieved that solid performance despite having flopped several late-stage trials, and the phase 2 PALOMA-1 trial for the Ibrance-Femara combo also failed to show a significant overall survival advantage.
Ibrance has enjoyed leader status because it entered the market one year ahead of Kisqali, and that’s a big advantage as physicians have gotten used to prescribing it, Hortobagyi explained. He pointed to the example of aromatase inhibitors, noting that even though many consider Femara a better drug, AstraZeneca’s Arimidex remains the most prescribed among three available options because it came to market first.
