In HR+, HER2- MBC
Verzenio: The ONLY CDK4 & 6 inhibitor to achieve significant OS improvement in combination with fulvestrant regardless of menopausal status1,2
9.4 months increase in median OS with Verzenio plus fulvestrant vs fulvestrant alone1
OS IN ITT POPULATION1,3
- Results are based on a preplanned interim analysis and considered to be definitive due to the occurrence of 77% (338/441) of the planned OS events needed for the final analysis1,4
- The percentage of deaths at the time of analysis was 47.3% (n=211) and 57.0% (n=127) in the Verzenio plus fulvestrant and fulvestrant alone arms, respectively1,4
- Primary endpoint of median PFS was met: 16.4 months (95% CI: 14.4-19.3) with Verzenio + fulvestrant vs 9.3 months (95% CI: 7.4-12.7) with fulvestrant alone (HR=0.553; 95% CI: 0.449-0.681; P<0.0001)3
- The percentage of events at the time of PFS analysis was 49.8% (n=222) and 70.4% (n=157) in the Verzenio plus fulvestrant and fulvestrant alone arms, respectively3
In HR+, HER2- MBC
Even women with visceral disease achieved overall survival results consistent with the overall study population1

Anna has visceral disease*
*Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).5
OS IN PATIENTS WITH VISCERAL DISEASE
- Prespecified subgroup analyses of PFS and OS were performed for stratification factors of disease site, including visceral disease
- Risk reduction reflective of the median. Analyses were not adjusted for multiplicity, and the study was not powered to test the effect of Verzenio plus fulvestrant among subgroups
Verzenio reduced risk of death by 33% in women with visceral disease1
In HR+, HER2- MBC
Even women with primary ET resistance achieved overall survival results consistent with the overall study population1

Pam has primary ET resistance
In MONARCH 2, primary ET resistance was defined as3:
- Relapse within 2 years of adjuvant ET
- Progressive disease within 6 months of first-line ET for MBC
OS IN PATIENTS WITH PRIMARY ET RESISTANCE1
- Prespecified subgroup analyses of PFS and OS were performed for the stratification factor of endocrine resistance (including primary ET resistance)
- Risk reduction reflective of the median. Analyses were not adjusted for multiplicity, and the study was not powered to test the effect of Verzenio plus fulvestrant among subgroups
Verzenio reduced risk of death by 31% in women with primary ET resistance1
Select Important Safety Information
Diarrhea occurred in 81% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 90% of patients receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 20% of patients receiving Verzenio alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection.
Diarrhea incidence was greatest during the first month of Verzenio dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1.
Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.
In HR+, HER2- MBC
Verzenio delayed time to chemotherapy1,6
EXPLORATORY ANALYSIS: TIME TO CHEMOTHERAPY (IN ITT POPULATION)1,6
- Time to chemotherapy: time from randomization to initiation of first post-discontinuation chemotherapy. Patients who died prior to receiving chemotherapy (n=111) did not contribute an event to this analysis1
- This analysis was not controlled for type I error, and the study was not powered to test this endpoint1
- Risk reduction reflective of the median
Verzenio reduced risk of progression to chemotherapy by 38% in the ITT population1
In HR+, HER2- MBC
Verzenio significantly improved median PFS in the ITT population7
PFS IN ITT POPULATION3
- The percentage of events at the time of PFS analysis was 49.8% (n=222) and 70.4% (n=157) in the Verzenio plus fulvestrant and fulvestrant alone arms, respectively3
Verzenio reduced risk of progression or death by 45% in the ITT population7
In HR+, HER2- MBC
Even women with visceral disease achieved improved median PFS consistent with the overall study population7,8
PREPLANNED SUBGROUP ANALYSIS: PFS IN WOMEN WITH VISCERAL DISEASE8
- The percentage of events at the time of PFS analysis in the ITT population was 49.8% (n=222) and 70.4% (n=157) in the Verzenio plus fulvestrant and fulvestrant alone arms, respectively3
- Prespecified subgroup analyses of PFS were performed for the stratification factor of disease site, including visceral disease7,8
- Risk reduction reflective of the median. Analyses were not adjusted for multiplicity and the study was not powered to test the effect of Verzenio plus fulvestrant among subgroups8
Verzenio reduced risk of progression or death by 52% in women with visceral disease8
In HR+, HER2- MBC
Even women with primary resistance achieved improved median PFS consistent with the overall study population7,8
PREPLANNED SUBGROUP ANALYSIS: PFS IN WOMEN WITH PRIMARY RESISTANCE8
- The percentage of events at the time of PFS analysis in the ITT population was 49.8% (n=222) and 70.4% (n=157) in the Verzenio plus fulvestrant and fulvestrant alone arms, respectively3
- Prespecified subgroup analyses of PFS were performed for the stratification factor of endocrine resistance7,8
- Risk reduction reflective of the median. Analyses were not adjusted for multiplicity and the study was not powered to test the effect of Verzenio plus fulvestrant among subgroups8
Verzenio reduced risk of progression or death by 55% in women with primary ET resistance7
MONARCH 2 trial design
MONARCH 2 included women with worse prognoses1,3,9*
All patients in the trial had prior endocrine therapy7§:
- 59% had ET in the adjuvant or neoadjuvant setting and had progressed from early-stage disease to metastatic7
- 38% had ET in the first-line metastatic setting and had progressed on first-line treatment7
*Patients with disease progression following ET who were at "higher risk" (defined as the presence of visceral disease† or primary ET resistance‡, which are associated with decreased overall survival) were included in the MONARCH 2 clinical trial.1,7,10-12
†Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).5
‡Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.3
§ET history was not available for 12 patients in the Verzenio arm and 5 patients in the placebo arm.7
Verzenio + fulvestrant: Phase III, randomized, double-blind, placebo-controlled trial (N=669)3,7
MONARCH 2 was a phase III, randomized, double-blind, placebo-controlled trial that enrolled 669 patients with HR+, HER2- MBC who progressed on or after ET. Pre/perimenopausal women (17%) were rendered postmenopausal prior to the study. Patients had received no chemotherapy and no more than 1 prior ET in the metastatic setting. Patients were randomized 2:1 to Verzenio + fulvestrant (n=446) or placebo + fulvestrant (n=223). Verzenio and placebo were dosed PO BID on a continuous dosing schedule until disease progression or unacceptable toxicity. 500 mg fulvestrant was administered by IM injection on days 1, 15, and 29 of the first month and once monthly thereafter. The primary endpoint was PFS. Key secondary endpoints were ORR, OS, and DoR.
References: 1. Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor–positive, ERBB2-negative breast cancer that progressed on endocrine therapy—MONARCH 2: a randomized clinical trial [published online September 29, 2019]. JAMA Oncol. 2020;6(1):116-124. doi:10.1001/jamaoncol.2019.4782. 2. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018;379:1926-1936. 3. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020. 4. Data on file. Lilly USA, LLC. DOF-AL-US-0088. 5. Data on file. Lilly USA, LLC. ONC20171128a. 6. Supplement to: Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor–positive, ERBB2-negative breast cancer that progressed on endocrine therapy—MONARCH 2: a randomized clinical trial [published online September 29, 2019]. JAMA Oncol. 2020;6(Suppl2):1-7. doi:10.1001/jamaoncol.2019.4782. 7. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35:2875-2884. 8. Data on file. Lilly USA, LLC. ONC20180103a. 9. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638-3646. 10. Yamamura J, Kamigaki S, Fujita J, Osato H, Komoike Y. The difference in prognostic outcomes between de novo stage IV and recurrent metastatic patients with hormone receptor-positive, HER2-negative breast cancer. In Vivo. 2018;32(2):353-358. 11. Gong Y, Liu Y-R, Ji P, Hu X, Shao ZM. Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study. Sci Rep. 2017;7:45411. 12. Wang R, Zhu Y, Liu X, et al. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19:1091.