New data from Novartis AG and Eli Lilly and Co. in separate studies have shown that women with a specific type of advanced breast cancer live longer when treated earlier with a class of drugs known as CDK4/6 inhibitors, or cyclin-dependent kinase inhibitor, and AstraZeneca PLC's Faslodex.
Overall survival in women with hormone receptor-positive, or HR+, and human epidermal growth factor 2-negative, or HER2-, advanced breast cancer increased in the Monarch 2 and the Monaleesa-3 studies, despite the fact that the trials included different patient populations, and differing CDK4/6 medications at varying stages of treatment.
Monarch 2 evaluated Eli Lilly and Co.'s Verzenio, also known as abemaciclib, plus Faslodex in patients with advanced breast cancer after endocrine therapy has failed and regardless of menopausal status. Monaleesa-3 study investigated Novartis AG's Kisqali, known as ribociclib, plus Faslodex as first-or second-line only in postmenopausal women.
Monaleesa-3 results showed that treatment with Kisqali and Faslodex significantly improves overall survival versus Faslodex alone in postmenopausal patients with HR+ HER2-advanced breast cancer, in first and second-line treatment. At 42 months, estimated rates of survival were 58% for the combination therapy and 46% for Faslodex alone.
The treatment's benefits were observed in women not previously treated with hormonal therapy, as well as in those who had become resistant to endocrine therapy.
"This is a significant, practice-changing report, in that we are now saying that patients with advanced breast cancer will have an overall survival benefit if they get [Kisqali] upfront at the time of their recurrence, even if they have not had any prior endocrine therapy at the time of presenting with metastatic disease," said Dennis Slamon, a professor at the University of California Los Angeles.
"The data from Monaleesa-3 clearly show that if postmenopausal patients receive this right up front there is a very significant benefit, not only in progression-free survival which had already been published, but now with this new report in overall survival — which is the hardest endpoint to reach, and the most important one in terms of making an impact on the disease," Slamon, who is the lead author of the study, said at the news conference.
"This is the first time we have seen improved overall survival with a combination of a CDK4/6 inhibitor plus [Faslodex] in first line," said Matteo Lambertini, a doctor at Italy's IRCCS Policlinico San Martino Hospital, University of Genoa. Uniquely, Monaleesa-3 is the only trial with a CDK4/6 inhibitor to include patients with endocrine sensitive as well as those with endocrine-resistant disease, he said in the news conference.
Separately, the Monarch 2 trial showed statistically and clinically meaningful improvement in overall survival with Eli Lilly's Verzenio plus AstraZeneca's Faslodex in women before, during and after menopause with HR+ HER2- advanced breast cancer that is resistant to hormonal therapy.
Previously released results from the Monarch 2 study showed significant improvement in progression-free survival for patients treated with the combination of abemaciclib plus Faslodex compared to Faslodex alone.
"Now, with further follow-up we have overall survival data showing a statistically significant and clinically meaningful improvement in overall survival with the combination," said George Sledge, a professor at Stanford University School of Medicine in the U.S.
"The main take-home message from this study — and from other similar studies — is that CDK4/6 inhibitors significantly prolong the time patients remain in remission and significantly improve overall survival. Therefore it is very reasonable to think of these as standard of care options for patients with metastatic breast cancer," he said at the news conference.
Nadia Harbeck, a professor at the University of Munich in Germany, said in the news conference that the results of Monarch 2 nicely complement those reported in Monaleesa-3 and strengthen the argument that treatment in the metastatic setting with a CDK4/6 inhibitor and endocrine therapy should start earlier because these drugs substantially improve patient outcomes.
Still, she noted that the studies were powered for progression-free survival and not for overall survival.
"This combined with Monaleesa 7 trial which we released at ASCO earlier in the year … these two have shown unparalleled consistent overall survival evidence," Novartis head of research and development John Tsai told reporters on a conference call ahead of the presentation. "It's a great advancement in terms of overall survival for patients with advanced breast cancer."
"With overall survival in two studies now — in Monaleesa 3 and Monaleesa 7 — including postmenopausal and peri-menopausal women, the evidence is clear in terms of understanding the full effects of overall survival balanced with the safety," Tsai said. "That's the key element we're trying to communicate here."
The European Society for Medical Oncology is holding its 2019 scientific meeting in Barcelona, where more than 3,900 study abstracts have been submitted for review by oncology professionals from around the world.
