MONALEESA-7 highlights survival benefit of ribociclib in premenopausal women with HR+ HER2- breast cancer
The addition of the CDK* 4/6 inhibitor ribociclib to endocrine therapy significantly extended overall survival (OS) in premenopausal women with HR+ HER2- advanced breast cancer, as evidenced in the phase III MONALEESA-7** trial.
“Ribociclib plus endocrine therapy resulted in a statistically significant longer OS compared with endocrine therapy alone,” said study author Dr Sara Hurvitz from the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, California, US.
These findings, in addition to the previous progression-free survival (PFS) findings, suggest a “substantial clinical benefit of ribociclib plus endocrine therapy as compared with endocrine therapy alone”, said Hurvitz and co-authors. [Lancet Oncol 2018;19:904-915; N Engl J Med 2019;doi:10.1056/NEJMoa1903765]
Study participants were 672 premenopausal or perimenopausal women (age <60 years) with HR+ HER2- advanced breast cancer who had received up to one prior line of chemotherapy but no prior endocrine therapy. They were randomized 1:1 to receive either ribociclib (600 mg/day on a 3-weeks-on, 1-week-off schedule) or placebo in addition to goserelin and a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole) or tamoxifen. Median treatment duration was about 2 years in the ribociclib arm and about 1 year in the placebo arm.
At a median follow up of 34.6 months, there was a 29 percent relative reduction in the risk of death among ribociclib compared with placebo recipients (median OS, not reached vs 40.9 months, hazard ratio [HR], 0.712, 95 percent confidence interval [CI], 0.535–0.948; p=0.00973). [ASCO 2019, abstract LBA1008]
Landmark analysis showed that OS at 36 months was 71.9 percent among ribociclib recipients compared with 64.9 percent among placebo recipients, while estimated OS at 42 months was 70.2 and 46.0 percent, respectively.
The OS results were consistent in a subgroup analysis which assessed the 495 patients who had received NSAI therapy (median OS, not reached vs 40.7 months, HR, 0.699, 95 percent CI, 0.501–0.976). Landmark analysis showed a 36-month OS of 72.2 and 64.6 percent, respectively, among ribociclib and placebo recipients, and an estimated 42-month OS of 69.7 and 43.0 percent, respectively.
The proportion of patients who received subsequent therapy was comparable between ribociclib and placebo recipients (69 percent vs 73 percent), with 10 and 19 percent of patients who discontinued ribociclib and placebo, respectively, receiving subsequent CDK 4/6 inhibitors.
Ribociclib recipients also had a longer time to receipt of first subsequent chemotherapy than placebo recipients (median, not reached vs 36.9 months, HR, 0.596), as well as a longer time to progression on subsequent therapy or death (PFS2; median, not reached vs 32.3 months, HR, 0.692).
More patients on ribociclib than placebo experienced grade 3–4 neutropenia (63.5 percent vs 4.5 percent) and hepatobiliary toxicity (11 percent vs 6.8 percent).
Safety remained consistent with the known tolerability profile of the drug, said Hurvitz.
“This is the first time a statistically significant improvement in OS has been observed with a CDK 4/6 inhibitor in combination with endocrine therapy in patients with HR+ HER2- advanced breast cancer,” said Hurvitz. “The benefit of ribociclib extends beyond initial treatment based on time to subsequent chemotherapy and PFS2.”
“Given the side effect profile being so manageable, it’s really a great day for women to know this drug can actually improve how long they are going to live,” she said.
“I think these data really are very supportive of our standard practice to utilize ribociclib in the front-line setting for patients with HR+ HER2- metastatic breast cancer and it provides the largest data set of premenopausal and perimenopausal women in this age group who have higher risk disease,” she told The Asco Post.
“I think it’s important data and hopefully will allow the therapy to be available globally in areas where treatments are not approved or available unless they have met OS benefit,” concluded Hurvitz.