Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) approved an expanded indication for Verzenio® (abemaciclib), in combination with endocrine therapy (ET), for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at a high risk of recurrence.

VERZENIO® is a kinase inhibitor indicated…in combination with an aromatase inhibitor as initial endocrine based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer…combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy…as monotherapy for the treatment of adult patients with HR positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Eli Lilly Canada Inc. (Lilly Canada) is pleased to announce the availability of VERZENIO (abemaciclib). VERZENIO is indicated for the treatment of estrogen and/or progesterone hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (mBC): in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy; in combination with fulvestrant for women with disease progression following endocrine therapy; and as a single agent for women with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Abemaciclib (Verzenios) is accepted for use within NHSScotland...for the treatment of women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor* as initial endocrine-based therapy, or in women who have received prior endocrine therapy...

Verzenios is indicated for the treatment of women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy.

The National Institute for Health and Care Excellence (NICE) on Friday recommended Eli Lilly's Verzenio (abemaciclib) be available to certain breast cancer patients in England following surgery. In a final draft guidance, NICE recommended Verzenio combined with hormone therapy for patients with hormone receptor-positive, HER2-negative, node-positive early-stage breast cancer who are at a high risk of recurrence following surgical tumor resection.

The Panel also recommends...abemaciclib for two years plus ET for ≥5 years may be offered to the broader intent-to-treat population of patients with resected, HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence, defined as having > 4 positive axillary lymph nodes, or as having 1-3 positive axillary lymph nodes and one or more of the following features: histologic grade 3 disease, tumor size > 5 cm, or Ki-67 index > 20%.

Abemaciclib plus fulvestrant is recommended as an option for treating hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer in adults who have had endocrine therapy only if...exemestane plus everolimus is the most appropriate alternative to a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor...

Two years of adjuvant abemaciclib in combination with endocrine therapy can be considered in patients with HR+/HER2-negative, high-risk breast cancer...HER2 Negative Breast Cancer: Invasive Breast Cancer…SYSTEMIC THERAPY FOR ER - AND/OR PR - POSITIVE RECURRENT OR STAGE IV (M1) DISEASE…HER2-Negative and Postmenopausal or Premenopausal Receiving Ovarian Ablation or Suppression…Preferred Regimens...Fulvestrant+ CDK4/6 inhibhitor ( Abemaciclib, palbociclib or ribociclib) (Category 1)

We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib….HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials...With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%.

Median OS (45.8m vs 37.2m; A vs P; HR: 0.784; 0.644-0.955) and OS rates (5yr: 41.2% vs 29.2%; 6yr: 34.7% vs 23.7%; A vs P) showed significant benefit for A….The results show significant OS and CFS benefits of abemaciclib therapy for ABC are confirmed and maintained and provide assurance of the safety of abemaciclib with longer-term use.

At median follow-up of 42 months, a numerically favorable IDFS effect was observed in both the <65 (270 vs 414 events; HR = 0.646, 95% CI: 0.554, 0.753) and ≥65 (66 vs 85 events; HR = 0.767, 95% CI: 0.556, 1.059) groups for abemaciclib + ET vs ET alone....In pts with high-risk EBC, adjuvant abemaciclib + ET showed treatment benefit across age subgroups with a manageable safety profile.

Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer.

...patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer...The median OS was 45.8 months in the abemaciclib arm and 37.2 months in the placebo arm (HR: 0.784; 95% CI: 0.644-0.955)….At the prespecified final OS analysis of the MONARCH 2 trial, with a median follow-up of 6.5 years, the statistically significant benefit previously demonstrated was confirmed and maintained.

Efficacy data from Cohort 1 demonstrate substantial evidence of benefit for adjuvant abemaciclib+ET in patients with HR+, HER2- early breast cancer at high risk of recurrence (ClinicalTrials.gov: NCT03155997 [monarchE]).

Consistent with the subgroup analysis of the East Asian population at primary cutoff, this analysis continues to show an improved PFS with the addition of abemaciclib to fulvestrant. Median PFS was 21.2 months in the abemaciclib arm...In conclusion, the survival benefit and the lower risk of death in the abemaciclib group indicated the clinical benefit of the regimen in East Asian patients with HR+, HER2− ABC.

In this subgroup, treatment with abemaciclib and ET demonstrated clinically meaningful benefit in IDFS (hazard ratio, 0.61; 95% CI, 0.47-0.80) and DRFS (hazard ratio, 0.61; 95% CI, 0.46-0.81), which corresponded with an absolute improvement of 6.6% in 2-year IDFS rates and 6.7% in 2-year DRFS rates....In the randomized clinical trial monarchE, treatment with adjuvant abemaciclib combined with ET demonstrated a clinically meaningful improvement in IDFS and DRFS for patients with HR+, ERBB2−, node-positive, high-risk early breast cancer who received NAC before trial enrollment.

Abemaciclib+ET demonstrated a clinically meaningful benefit in reducing the risk of developing an IDFS event by 32% (absolute benefit of 5.7% at 3Y) and a DFRS event by 33% (4.5% absolute benefit at 3Y)(Table). Within C1, consistent treatment benefit in IDFS and DRFS was seen in subgroups of patient and disease characteristics. C1 data demonstrate substantial evidence of the benefit of adjuvant abemaciclib+ET in patients with HR+, HER2- EBC at high risk of recurrence...

Patient (Pts) with HR+, HER2- tumors....For preM pts, abemaciclib + ET resulted in a 42.7% and 40.8% reduction in risk of developing an IDFS and DRFS event, respectively….Abemaciclib + ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS vs. ET alone regardless of menopausal status, with a numerically greater benefit in the preM population.

At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]....Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer...

This global, phase 3, open-label trial, randomized (1:1) 5637 patients to adjuvant ET for ≥5 years +/- abemaciclib for 2 years....At the PO analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event (HR=0.71, 95% CI: 0.58, 0.87; nominal p=0.0009).... Abemaciclib+ET significantly improved IDFS in patients with HR+, HER-, node-positive, high risk EBC...

Abemaciclib plus fulvestrant in participants with HR+/HER2- advanced breast cancer: A pooled analysis of the endocrine therapy naïve (EN) participants in MONARCH 2...In the pooled EN cohort, confirmed ORR was 59.1% (95% CI 49.9-68.3)….The primary analysis of confirmed ORR compares favorably with previously reported ORR for fulvestrant monotherapy in participants with a similar disease state.

...median PFS was 28.6 months in the abemaciclib plus fulvestrant arm compared with 10.26 months in the placebo plus fulvestrant arm (HR 0.477; 95% CI 0.302-0.755). A numerical OS benefit was observed with abemaciclib plus fulvestrant compared to fulvestrant alone (HR 0.689; 95% CI 0.379-1.252, median, not reached vs 47.3 months). Improvements were also observed for the exploratory outcomes of PFS2 (HR 0.599), TTC (HR 0.674), and CFS (HR 0.642) with the addition of abemaciclib to fulvestrant...use of abemaciclib plus fulvestrant (with ovarian suppression) as an effective treatment option for premenopausal patients with HR+, HER2- ABC who are ET-resistant.

...The addition of abemaciclib to ET resulted in an improvement in distant relapse-free survival (DRFS) (HR: 0.609, 95% CI: 0.459, 0.809), with 2-year DRFS rates of 89.5% and 82.8%, respectively. Safety profile was similar to the overall safety population.Patients with HR+, HER2- EBC who received NAC were noted to be at a higher risk of recurrence. In this subgroup, abemaciclib combined with ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS, which was numerically greater than in the ITT population. Safety data were consistent with abemaciclib safety profile.

...The addition of abemaciclib to ET resulted in an improvement in distant relapse-free survival (DRFS) (HR: 0.609, 95% CI: 0.459, 0.809), with 2-year DRFS rates of 89.5% and 82.8%, respectively. Safety profile was similar to the overall safety population.Patients with HR+, HER2- EBC who received NAC were noted to be at a higher risk of recurrence. In this subgroup, abemaciclib combined with ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS, which was numerically greater than in the ITT population. Safety data were consistent with abemaciclib safety profile.

Eli Lilly and Company...today announced additional data from a pre-planned primary outcome analysis from the Phase 3 monarchE trial that showed Verzenio® (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) decreased the risk of breast cancer recurrence by 28.7 percent compared to standard adjuvant ET alone for people with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high risk early breast cancer (HR: 0.713; 95% CI: 0.583, 0.871; p = 0.0009)...

We report age-specific outcomes from exploratory subgroup analyses of the MONARCH 2 and 3 trials in HR+, HER2- ABC...A consistent PFS benefit was observed with abemaciclib+ET vs PBO+ET across all subgroups in both studies...

ITT population, updated PFS was 28.2 vs 14.8 months (HR [95% CI]: 0.525 [0.415, 0.665]; p< .0001) in the abemaciclib vs placebo arms...Addition of abemaciclib to AI prolonged PFS2 and TCT in the ITT population and all prognostic subgroups...

Abemaciclib plus ET demonstrated superior IDFS versus ET alone (P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively….Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.

...Abemaciclib plus ET demonstrated a statistically significant improvement in IDFS versus ET alone (p=.0096, HR: 0.747, 95% CI: 0.598, 0.932), corresponding to a 25.3% reduction in the risk of an IDFS event. The 2-year IDFS rates were 92.2% vs 88.7%, respectively....Abemaciclib when combined with ET is the first CDK4 & 6 inhibitor to demonstrate a statistically significant improvement in IDFS in patients with HR+, HER2-, high risk EBC.

Subgroup analyses showed no statistically significant difference of PFS among three CDKi: palbociclib vs ribociclib (HR 0.55, 95% CI 0.49-0.60, P = 0.34), palbociclib vs abemaciclib (HR 0.53, 95% CI, 0.47-0.59, P = 0.61), and ribociclib vs abemaciclib (HR 0.56, 95% CI, 0.51-0.62, P = 0.72). CDKi combined with ET can significantly prolong PFS and improve the ORR, CBR and OS in patients with HR+/HER2- ABC. However, the advantage of different CDKi has not been established.

In the MONARCH 2 trial (NCT02107703), 669 women without prior chemotherapy for ABC received abemaciclib (or placebo) + fulvestrant + goserelin. Among all patients, 59% and 38% had 0 and 1 prior lines of ET for metastatic disease. In premenopausal women (abemaciclib, n = 72; placebo, n = 42), abemaciclib prolonged PFS...safety and efficacy established in the MONALEESA-7 trial of premenopausal women and premenopausal subsets of the PALOMA-3 and MONARCH 2 trials support using CDK4/6 inhibitor combination therapy in these patients.

Treatment with abemaciclib plus fulvestrant resulted in a statistically significant and clinically meaningful median OS improvement of 9.4 months for patients with HR-positive, ERBB2-negative ABC who progressed after prior ET regardless of menopausal status.

The ORR was 61.0% in the abemaciclib arm versus 45.5% in the placebo arm (measurable disease, p = .003). The median duration of response was longer in the abemaciclib arm (27.39 months) compared to the placebo arm (17.46 months).

Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

...Have a diagnosis of HR+, HER2- breast cancer...

...The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases...

Of the patients where response data were available (n = 51), rw intracranial clinical benefit rate (CBR; complete response [CR]/partial response [PR]/stable disease [SD]≥24 weeks of abemaciclib initiation) was 62.7%....In this real-world study, most patients with brain metastases secondary to HR+/HER2- MBC who initiated abemaciclib treatment received SRS or WBRT prior to or concurrent with abemaciclib initiation. While the clinical outcomes, rwPFS and intracranial CBR were encouraging...

This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2− mBC receiving abemaciclib in US-based community oncology settings...The CBR for the overall population was 53%, with 48% achieving stable disease....The median PFS was 329 days (95% CI 266, 386).

A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included….With a median follow-up of 15.5 months, abemaciclib + endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598–0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively.

Finally, data from a cohort of 52 patients indicated that patients with HR-positive/HER2-negative MBC who progressed on palbociclib-containing regimens can exhibit a meaningful overall clinical benefit from abemaciclib-based therapy when administered after palbociclib. These findings provide the rationale for clinical trials evaluating the benefit of abemaciclib treatment following progression on a prior CDK4/6i.

Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%)....For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%)….Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients.

Patients from 12 referral Italian hospitals with HR+/HER2- aBC who received abemaciclib were included….Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively....Efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in elderly population and patients with comorbidities.

To describe abemaciclib use in patients with hormone receptor-positive, human epidermal growth factor receptor-negative (HR+/HER2−) metastatic breast cancer (mBC) who participated in the Named Patient Use program (NPU) in Spain....A CR was achieved in 2.3% of patients receiving abemaciclib monotherapy and 11.8% of patients receiving combination therapy, with a PR in 23.3% and 23.5%, respectively. ORR at the end of follow-up was 25.6% and 35.3% for the monotherapy and combination therapy groups, respectively.

Evaluation of tumor response was available for 171 patients, 30.4% of whom had complete/partial response. Median PFS was 13.0 months (95% CI 10.1-15.8 months)….In a routine clinical practice setting in Japan, patients with HR + , HER2- MBC appear to benefit from abemaciclib treatment in terms of treatment response and median PFS, with the results broadly reflecting the evidence demonstrated in clinical trials.

A multicenter retrospective observational chart review was undertaken of women in the United Kingdom (UK) with HR+, HER2- ABC/MBC treated with ABE-containing regimens...Best tumor response (136 patients); 0.7% had complete response, 27.9% had partial response, 59.6% had stable disease and 11.8% had disease progressed.

Consistent with reported results for the overall ITT population, abemaciclib combined with ET demonstrated clinically meaningful and sustained IDFS and DRFS benefits among Chinese pts with HR+, HER2-, high risk EBC and continued separation of the IDFS and DRFS curves. The OS data remain immature and follow-up is ongoing.

The clinically meaningful benefit of adjuvant abemaciclib added to ET in HR+, HER2-, node-positive, high-risk EBC persists beyond completion of abemaciclib therapy, yielding an increase in absolute IDFS and DRFS benefit at 4 yrs.

We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2- EBC in monarchE....Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates….Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population.

IDFS and DRFS data illustrate a sustained benefit beyond the treatment period. In the ITT population, the HR for IDFS was 0.664 (95% CI: 0.578, 0.762) and DRFS was 0.659 (95% CI: 0.567, 0.767)…there was a lower number of deaths observed in the abemaciclib plus ET arm compared to the ET alone arm (157 [5.6%] vs 173 [6.1%], HR 0.929 [95% CI: 0.748, 1.153], p = 0.503), suggesting that the robust benefit in IDFS and DRFS began to translate into a numerically favorable OS HR....The clinically meaningful benefit of adjuvant abemaciclib added to ET in HR+, HER2-, node- positive, high-risk EBC persists beyond completion of abemaciclib therapy, yielding an increase in absolute IDFS and DRFS benefit at 4 yrs.

Median OS was 24.2 months in the A + T arm, 20.8 months in A-150, and 17.0 months in A-200 (A + T versus A-200: HR 0.62; 95%CI [0.40, 0.97], P = 0.03...The addition of tamoxifen to abemaciclib demonstrated greater OS benefit than monotherapy. This study confirmed the single-agent activity of abemaciclib in heavily pretreated women with endocrine-refractory HR + , HER2– MBC, as well as the previously reported primary PFS and ORR results...

To assess the safety profile and clinical outcomes of a consecutive cohort of HR+/HER2- MBC patients treated with abemaciclib...The median progression-free survival (PFS) was 6 months (95%CI 3.5 – 10). 5 patients still continue on abemaciclib. Of these, 1 patient with hepatic metastases achieved complete response. Clinical benefit rate (CBR) at 24 weeks was seen in 5 patients out of 8 evaluable patients...Abemaciclib may result an effective and safe treatment option in MBC patients previously treated with palbociclib or ribociclib.

A total of 839 patients received a documented second-line therapy after progression on first-line CDK4/6i treatment....Continuation of the CDK4/6i was associated with improved rwPFS (HR 0.48, 95% CI 0.43-0.53, P < .0001) and OS (HR 0.30, 95% CI 0.26-0.35, P < .0001) compared to chemotherapy....While prospective data are needed, analysis of real-world data suggests a survival benefit for continuation of a CDK4/6i beyond frontline progression for patients with HR+/Her2- MBC.

Sixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15)....Abemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC.

At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01)….Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2− node positive EBC.

Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease....Abemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC.

We retrospectively identified HR-positive, HER2-negative ABC patients who received abemaciclib...Abemaciclib produced clinical benefit rate of 82.8% and overall response rate of 47.2% in 163 patients assessed. Overall, median progression-free survival (PFS) was 6.4 months (95% confidence interval [CI] 4.4-7.8) and median overall survival (OS) was 8.8 months (95% CI 7.6-10.6).

The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2- BC....subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59-29.61, p < 0.001; palbociclib: OR = 7.39, 95% CI = 1.26-43.40, p = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41-20.11, p < 0.001).

In MONARCH 3, continuous dosing of abemaciclib with an aromatase inhibitor (AI) conferred significant clinical benefit to postmenopausal women with HR+, HER2- advanced breast cancer...In the intent-to-treat population, after median follow-up of approximately 39 months, the updated PFS was 28.2 versus 14.8 months (hazard ratio [HR], 0.525; 95% confidence interval, 0.415-0.665) in abemaciclib versus placebo arms, respectively.

There was also a numerical improvement in distant relapse free survival (DRFS) [HR (95% CI) = 0.758 (0.455, 1.264)], with 2-year DRFS rates of 94.4% vs 91.7%. The median txt duration of abemaciclib was 17.7 months. In the abemaciclib arm, the most frequent adverse event (AE) was diarrhea (89.5%), most were G1/2 (55.8%/28.7%). More G≥3 AEs and serious AEs were observed with abemaciclib+ET vs ET (53.5% vs 10.5% and 12.1% vs 6.3%), with neutropenia (31.5%) being the most frequent G≥3 AE. Interstitial lung disease occurred in 6.6% pts, G≥3 in 0.3% pts. G≥3 ALT and AST increases occurred in 4.2% and 3.1% pts, respectively.14.5% of abemaciclib-treated pts discontinued abemaciclib or all txt due to AEs.In pts from Asia with HR+, HER2-, high-risk EBC, abemaciclib plus standard adjuvant ET led to a clinically meaningful improvement in IDFS and DRFS, consistent with benefits demonstrated in the ITT population. Safety was consistent with the known safety profile of abemaciclib. Abemaciclib is the first CDK4 & 6 inhibitor to demonstrate effective and tolerable txt in pts with high-risk EBC

Patients with HR+/HER2- metastatic breast cancer treated with abemaciclib in combination with ET...were identified.... In patients with measurable disease, ORR was 55.7%, significantly higher in first line compared to second line (70.5% vs 17.7%, p<0.001)....abemaciclib was associated with a meaningful rate of objective response, with a favourable safety profile.

....the PFS treatment benefit [HR (95% CI)] of abemaciclib (vs comparators) was 0.75 (0.57-1.0)...patients diagnosed with HR+/HER2- advanced breast cancer treated with abemaciclib...had a smaller PFS benefit from abemaciclib (vs comparator) than patients with intermediate/high physical function.

HR+/HER-2- ABC patients treated with CDK4/6 inhibitors combined with ET had significantly prolonged progression-free survival (PFS) and improved objective response rate (ORR) and clinical benefit rate (CBR)....the patients in experimental intervention groups were treated with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib)...groups treated with CDK4/6 inhibitors (palbociclib, ribociclib or abemaciclib) combined with ET had a prolonged PFS compared with the endocrine monotherapy groups (HR = 0.55, 95% CI: 0.50–0.60, p < 0.001...

We identified 87 patients with HR+ MBC from 6 medical centers in the United States who received abemaciclib after prior progression on a palbociclib- or ribociclib-containing regimen in the metastatic setting….Median PFS on abemaciclib-based therapy in the 87 patients was 5.3 months (95% CI, 3.5–7.8 months; Figure 1A).

nextMONARCH was a multicenter, randomized, open-label phase II trial of abemaciclib in women with heavily pretreated HR+, HER2- MBC whose disease progressed on or after ET and chemotherapy. Patients were randomized 1:1:1 to abemaciclib 150 mg + tamoxifen 20 mg (A+T), or abemaciclib 150 mg (A-150) or abemaciclib 200 mg plus prophylactic loperamide (A-200)....Median OS was 24.2 months in the A+T arm, compared to 20.8 months in A-150, and 17.0 months in A-200 (A+T vs. A-150: HR 0.620 (95% CI [0.397, 0.969] p=0.034); A-150 vs. A-200: HR 0.956 (95% CI [0.635, 1.438] p=0.832))....Addition of tamoxifen to abemaciclib provided a statistically significant median OS improvement compared to abemaciclib monotherapy in this heavily pretreated HR+, HER2- MBC patient population.

Abemaciclib was associated with an iCBR of 24% in patients with heavily pretreated HR+, HER2- MBC.

Adding abemaciclib/palbociclib/ribociclib to AI (HR: 0.55, 95% CI 0.48-0.64) or abemaciclib/palbociclib to fulvestrant (HR: 0.49, 95% CI 0.37-0.63) improved significantly the PFS of metastatic HR+ Her 2- breast cancers regardless menopausal status and site of metastasis.

Patients (pts) in 6 cohorts received abemaciclib 150-200 mg every 12 hours (Q12H) with letrozole 2.5 mg/d (Part A), anastrozole 1 mg/d (Part B), tamoxifen 20 mg/d (Part C), exemestane 25 mg/d (Part D), exemestane 25 mg/d + everolimus 5 mg/d (Part E)...Combinations of abemaciclib with endocrine therapies demonstrate manageable safety and early clinical evidence of antitumor activity.

A total of 132 patients with HR+/HER2− MBC were enrolled….Abemaciclib demonstrated single-agent activity with 26 of 132 patients achieving a confirmed PR for an ORR of 19.7% (95% CI, 13.3–27.5; 15% not excluded)...

We report a case of a postmenopausal woman with HR-positive and HER2-negative advanced BC...We then tried abemaciclib in the 11th-line setting, where it induced a response that lasted 16 months.

We report the case of a 72‒year‒old woman with ER(+), PgR(+), HER2(-)metastatic breast cancer...She was subsequently switched to abemaciclib(150 mg twice/daily po)with fulvestrant as third‒line therapy, resulting in a decrease in the same liver lesions. She has continued treatment for 12 months. Based on this case, abemaciclib may be clinically useful for breast cancer.

A 73- year-old woman was diagnosed by chance with late recurrence of HR+ breast cancer 21 years…she was on a year- long administration of anastrozole and an optimal dose of abemaciclib(100 mg bid)...1 year of treatment, she could only maintain the treatment for up to 13 months. After then, no recurrence has been detectable for 6 months so far.