First-line ribociclib and endocrine therapy

The phase III placebo-controlled MONALEESA-2 trial (NCT01958021) randomly assigned 668 patients to receive either first-line ribociclib plus letrozole or placebo plus letrozole.[12,13]

The phase III placebo-controlled MONALEESA-2 trial (NCT01958021) randomly assigned 668 patients to receive either first-line ribociclib plus letrozole or placebo plus letrozole.[12,13]

The primary end point (investigator-assessed PFS) was met. A preplanned interim analysis was performed after 243 patients had disease progression or died, and median duration of follow-up was 15.3 months. After 18 months, the PFS rate was 63.0% (95% CI, 54.6%–70.3%) in the ribociclib group and 42.2% (95% CI, 34.8%–49.5%) in the placebo group.[12]

The phase III placebo-controlled MONALEESA-2 trial (NCT01958021) randomly assigned 668 patients to receive either first-line ribociclib plus letrozole or placebo plus letrozole.[12,13]

OS was a secondary end point. A protocol-specified final analysis of OS was published after 400 deaths and a median follow-up of 6.6 years. Patients who received ribociclib plus letrozole had a significant OS benefit compared with patients who received placebo plus letrozole. Median OS was 63.9 months in the ribociclib group and 51.4 months in the placebo group (HRdeath, 0.76; 95% CI, 0.63–0.93; two-sided P = .008).[14][Level of evidence A1]

The phase III placebo-controlled MONALEESA-2 trial (NCT01958021) randomly assigned 668 patients to receive either first-line ribociclib plus letrozole or placebo plus letrozole.[12,13]

Grade 3 to 4 neutropenia occurred in 63.8% of patients in the ribociclib group and 1.2% of patients in the placebo group. Grade 1 to 2 nausea, infection, fatigue, and diarrhea were also noted. Grade 3 to 4 hepatobiliary toxic effects occurred in 14.4% of patients who received ribociclib and 4.8% of patients who received placebo. Prolonged QTcF interval occurred in 4.5% of patients in the ribociclib group and 2.1% of patients in the placebo group.

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15]

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15]

The primary end point (investigator-assessed PFS) was met. At the time of final analysis for PFS, the median PFS for the ribociclib group was 20.5 months versus 12.8 months in the placebo group (HR, 0.593; 95% CI, 0.480–0.732; P < .001).[15][Level of evidence B1]

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15]

OS was superior in the ribociclib group (HR, 0.724; 95% CI, 0.568–0.924; P = .004). The result crossed the prespecified stopping boundary (P = .011) for superior efficacy. Results were similar in all subgroups.[16][Level of evidence A1]

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15]

Adverse events were similar to those in other studies of CDK4/6 inhibitors.

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15] › Adverse events were similar to those in other studies of CDK4/6 inhibitors.

Grade 3 to 4 neutropenia occurred in 53.4% of patients in the ribociclib group and 0.0% of patients in the placebo group.

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15] › Adverse events were similar to those in other studies of CDK4/6 inhibitors.

The rate of febrile neutropenia was 1.0% in the ribociclib group and 0% in the placebo group.

Ribociclib has also been tested in combination with fulvestrant in postmenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer. The MONALEESA-3 trial (NCT02422615) included patients receiving first-line or second-line therapy. This phase III, placebo-controlled trial randomly assigned 726 patients in a 2:1 ratio to receive ribociclib plus fulvestrant or placebo plus fulvestrant.[15] › Adverse events were similar to those in other studies of CDK4/6 inhibitors.

An increase in QTcF interval of more than 60 milliseconds from baseline was observed in 6.5% of patients in the ribociclib arm and 0.4% in the placebo arm.

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo.

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo.

The primary end point (investigator-assessed PFS) was met. At the time of final analysis for PFS, the median PFS for the ribociclib group was 23.8 months versus 13.0 months in the placebo group (HR, 0.55; 95% CI, 0.44–0.69; P < .0001).[17][Level of evidence A3]

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo.

OS was a secondary end point. The combination of ribociclib plus endocrine therapy was associated with longer OS than was endocrine therapy alone (42-month OS, 70.2% vs. 46%; HRdeath, 0.71; 95% CI, 0.54−0.95; P = .01).[18][Level of evidence A1] The survival benefit was observed both in patients who received an AI plus goserelin and in those who received tamoxifen, but it was not statistically significant in the much-smaller tamoxifen group.

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo.

Adverse events were similar to those in other studies of CDK4/6 inhibitors.

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo. › Adverse events were similar to those in other studies of CDK4/6 inhibitors.

Grade 3 to 4 neutropenia occurred in 61% of patients in the ribociclib group and 4% of patients in the placebo group.

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo. › Adverse events were similar to those in other studies of CDK4/6 inhibitors.

The rate of febrile neutropenia was 2.0% in the ribociclib group and 1.0% in the placebo group.

Ribociclib was also assessed in the first-line setting in a study conducted solely in premenopausal or perimenopausal women receiving either tamoxifen or a nonsteroidal aromatase inhibitor (AI) plus goserelin.[17] In the MONALEESA-7 trial (NCT02278120), 672 premenopausal patients with HER2-negative hormone receptor–positive, recurrent or metastatic breast cancer, who had not received endocrine therapy for advanced disease, were randomly assigned in a 1:1 ratio to ribociclib or placebo. › Adverse events were similar to those in other studies of CDK4/6 inhibitors.

An increase in QTcF interval of more than 60 milliseconds from baseline was observed in 10.0 % of patients in the ribociclib arm and 2.0% in the placebo arm. Sixty-millisecond increases were more common in patients receiving tamoxifen (16% on ribociclib and 7% on placebo).