Verzenios ® (abemaciklib)

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Verzenios® ▼ (abemaciclib): MONARCH 2 - Användning i combination med fulvestrant i avancerad bröstcancer

Abemaciclib i kombination med fulvestrant demonstrerar effekt med en progressionsfri överlevnad på 16,4 månader i abemaciclib-armen jämfört med 9,3 månader i placebo-armen.

Results of the MONARCH 2 Trial

Efficacy

The median relative dose intensity was 97.7% for the abemaciclib arm and 99.8% for the placebo arm.1 Dose reductions due to an adverse reaction occurred in 43% of patients in the abemaciclib arm.2 Median follow-up was 47.7 months.3

The efficacy analysis is presented in Table 1 and Table 2.

Table 1. Investigator-Assessed Efficacy ITT Analysis in MONARCH 23

 

Abemaciclib + Fulvestrant

Placebo + Fulvestrant

Progression-free survival

N=446

N=223

Median, months

16.9

9.3

Hazard ratio (95% CI)

0.536 (0.445, 0.645) 

P value

<.001

Overall survival

N=446

N=223

Median, months

46.7

37.3

Hazard ratio (95% CI)

0.757 (0.606, 0.945)

P value

.01

Abbreviation: ITT = intent-to-treat.

Table 2.  Investigator-Assessed Objective Response ITT Analysis in MONARCH 22


Abemaciclib + Fulvestrant

Placebo + Fulvestrant

Objective response for ITT population

N=446

N=223

Objective response rate, %

35.2

16.1

Complete response, %

3.1

0.4

Clinical benefit rate, %

72.2

56.1

Objective response for patients with measurable disease

N=318

N=164

Objective response rate, %

48.1

21.3

Complete response, %

3.5

0

Clinical benefit rate, %

73.3

51.8

Abbreviation: ITT = intent-to-treat.

Overall survival in the ITT population is presented in Figure 1.

Figure 1. Overall Survival ITT Population in MONARCH 23

Abbreviations: ITT = intent-to-treat; OS = overall survival.
Note: 9.4 month OS benefit.

The median duration of response was 22.8 months in the abemaciclib arm vs 13.9 months in the placebo arm.1

Abemaciclib plus fulvestrant demonstrated improved PFS across all patient subgroups analyzed and is presented in Figure 2 and Figure 3.2,4,5

Figure 2. Progression-Free Survival by Patient Subgroup (1 of 2)2

Abbreviations: ET = endocrine therapy; HR = hazard ratio; PgR = progesterone receptor.
Note: HR is for abemaciclib vs placebo; HRs are indicated by diamonds and are proportional to patient subgroup size; HRs are unstratified, except overall which is stratified by metastatic site and ET resistance; interaction p value is from a model with arm, the subgroup variable and arm x subgroup interaction term.

Figure 3. Progression-Free Survival by Patient Subgroup (2 of 2)2

Abbreviations: ECOG PS = Eastern Cooperative Oncology Group performance status; HR = hazard ratio.
Note: HR is for abemaciclib vs placebo; HRs are indicated by diamonds and are proportional to patient subgroup size; HRs are unstratified, except overall which is stratified by metastatic site and ET resistance; interaction p value is from a model with arm, the subgroup variable and arm x subgroup interaction term.

While all subpopulations benefited from the addition of abemaciclib to ET regardless of prognosis, in a subgroup analysis of patients in MONARCH 2 and MONARCH 3, substantial benefit of abemaciclib (characterized by large increases in PFS [HRs = 0.4 - 0.5] and ORR [>30%]) was observed in poor prognosis subgroups with liver metastases, progesterone receptor-negative tumors, and high-grade tumors.5

Abemaciclib plus fulvestrant provided a statistically significant improvement in OS. The OS benefit was consistent across subgroups, including patients with poor prognostic factors such as visceral metastasis (HR=0.675) and primary ET resistance (HR=0.686).3

Results of OS by metastatic site can be seen in Figure 4.

Figure 4. Overall Survival by Metastatic Site3,6

Abbreviations: NR = not reached; OS = overall survival.
Note: Interaction p value=.424.
Site of Metastases: visceral: lung, liver, pleural, or peritoneal (in the presence or absence of bone metastases); bone only: only in bone; other: other soft tissue sites (in the presence or absence of bone metastases).

Primary ETR and secondary ETR OS data is presented in Figure 5.

Figure 5. Overall Survival by Resistance to Endocrine Therapy3,6