Two New Studies Report Significant Benefit With CDK4/6 Inhibitors in Advanced Breast Cancer


Treatment with a CDK4/6 inhibitor plus fulvestrant found to improve overall survival in women with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer.

Treatment with a CDK4/6 inhibitor plus fulvestrant (Faslodex) was found to improve overall survival (OS) in women with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer, according to new data from 2 studies reported at the EMSO Congress 2019.

The 2 studies included various patient populations as well as different CDK4/6 inhibitors used as multiple lines of therapy: MONARCH 2 evaluated abemaciclib (Verzenio) plus fulvestrant in patients with advanced breast cancer after failure of endocrine therapy and regardless of menopausal status; the MONALEESA-3 study investigated ribociclib (Kisqali) plus fulvestrant as first- or second-line only in postmenopausal patients.

The results give the treating physician the full spectrum of choice of CDK4/6 inhibitor for each individual patient, although the 2 CDK4/6 inhibitors have slightly different management requirements and toxicity profiles.


First-line, as well as second-line, treatment with the CDK4/6 inhibitor ribociclib plus fulvestrant significantly improved OS in postmenopausal patients with HR+ HER2- advanced breast cancer compared with fulvestrant alone, according to results from the study. The benefits with ribociclib plus fulvestrant were seen in women previously untreated with hormonal therapy as well as in those who had become resistant to endocrine therapy.

According to Dennis J Slamon, MD, PhD, the combined data set of MONALEESA-3 and -7, which total approximately 1400 patients, represents the largest body of evidence of OS benefit for any CDK4/6 inhibitor.

“These data demonstrate a consistent, meaningful prolongation of survival with ribociclib with multiple endocrine therapy partners, regardless of menopausal status,” Dr Slamon said.

According to Dr Slamon, if postmenopausal patients receive this therapy right up front there is a very significant benefit, not only in progression free survival (PFS), but with OS.

MONALEESA-3 is the only trial with a CDK4/6 inhibitor to include patients with endocrine sensitivity as well as those with endocrine-resistant disease.


MONARCH 2 showed statistically and clinically meaningful improvement in OS with the CDK4/6 inhibitor abemaciclib plus fulvestrant in pre- and peri-, as well as in postmenopausal women with HR+, HER2- advanced breast cancer resistant to hormonal therapy.

Results of this study presented 2 years ago showed significant improvement in PFS for patients treated with the combination of abemaciclib plus fulvestrant compared with fulvestrant alone. In this follow-up, the OS data show a statistically significant and clinically meaningful improvement in OS with the combination.

The study, which was presented by lead author George W. Sledge Jr, MD, showed a median OS benefit of 9.4 months. This benefit was consistent across subgroups, including patients with poor prognostic factors, sch as visceral metastasis and primary endocrine therapy resistance, Dr Sledge reported.

Additionally, 17% of patients in the abemaciclib arm remained on treatment versus 4% in the placebo arm after a median follow-up of 47.7 months at the time of analysis.

Based on an exploratory anaylsis, Sledge also noted that the addition of abemaciclib significantly delayed the need for subsequent chemotherapy.

Follow-up of the study will further characterize OS benefit and exploratory efficacy endpoints, Sledge concluded.

Commenting on the relevance of the new studies, Nadia Harbeck, MD, PhD, professor at University of Munich, Germany, said, “The results of MONARCH 2 nicely complement those reported in MONALEESA-3. Abemaciclib is the third CDK4/6 inhibitor to show an overall survival benefit in advanced HR+ HER2- breast cancer. Together with the data we have seen before with palbociclib and ribociclib, these new data strengthen the argument that we should start treatment in the metastatic setting with a CDK4/6 inhibitor plus endocrine therapy because these drugs substantially improve patient outcomes compared to anti-hormonal treatment alone.”


  • LBA6_PR- MONARCH 2: Overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2- advanced breast cancer. Presented by George W. Sledge Jr, MD at ESMO Congress 2019. September 29, 2019. Barcelona, Spain.
  • LBA7_PR- Overall survival results from the phase 3 MONALEESA-3 study of fulvestrant ± ribociclib in postmenopausal patients with HR+/HER2- advanced breast cancer. Presented by Dennis J. Slamon at ESMO Congress 2019. September 29, 2019. Barcelona, Spain.

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