Science - USA (2022-01-14)

Fasslet al.,Science 375 , eabc1495 (2022) 14 January 2022 10 of 19

CDK4/6inhibitor

Trial name

Trial details

Treatment

Patients

Outcome

Ref.

Other outcomes

..............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................Abemaciclib

MONARCH 1

Phase 2 trial

Abemaciclib as asingle agent

Women with HR

+/HER2

• 
  

metastatic breast cancerwho had progressed on orafter prior endocrine therapyand had 1 or 2 chemotherapyregimens in the metastaticsetting

Abemaciclib exhibited promising activityin these heavily pretreated patientswith poor prognosis; medianPFS was 6.0 months and overallsurvival 17.7 months

(^136

)

The most common adverse eventswere diarrhea, fatigue, andnausea (

136

)

...............................................................................................................................................................................................................................................................................................................................................................................................................................................Abemaciclib

MONARCH 2

Double-blindphase 3

Abemaciclib incombinationwith fulvestrant

Women with HR

+/HER2

• breast

cancer who had progressedwhile receiving endocrinetherapy, or while receivingfirst-line endocrine therapy formetastatic disease

Addition of abemaciclib significantlyincreased PFS from 9.3 months inthe placebo-fulvestrant to 16.4 inthe abemaciclib-fulvestrant group;median overall survival was alsoextended from 37.3 monthsto 46.7 months

(^129

,^134

)

...............................................................................................................................................................................................................................................................................................................................................................................................................................................Abemaciclib MONARCH 3

Randomizedphase 3double-blind

Abemaciclib plusan aromataseinhibitor(anastrozoleor letrozole)

Postmenopausal womenwith advanced HR

+/HER2

• 
  

breast cancer who hadno prior systemic therapyin the advanced setting

Addition of abemaciclib prolongedPFS from 14.8 months (inthe placebo-aromataseinhibitor group) to 28.2 months(abemaciclib-aromataseinhibitor group)

(^130

,^131

)

...............................................................................................................................................................................................................................................................................................................................................................................................................................................Abemaciclib MonarchE

Phase 3 study Endocrine with

or withoutabemaciclib

Patients with HR

+/HER2

• 
  

lymph node

• positive,

high-risk earlybreast cancer

Preliminary analysis indicates thataddition of abemaciclib resultedin a significant improvement ofinvasive disease-free survivaland of distant relapse-free survival

(^137

)

...............................................................................................................................................................................................................................................................................................................................................................................................................................................Trilaciclib

Randomizedphase 2 study

Chemotherapy alone(gemcitabine andcarboplatin),versus concurrentadministration oftrilaciclib pluschemotherapy,versusadministration oftrilaciclib prior tochemotherapy(to mitigate thecytotoxic effect ofchemotherapy onbone marrow)

Patients with recurrent ormetastatic triple-negativebreast cancer who had nomore than two previouslines of chemotherapy

Addition of trilaciclib did not offerdetectable myeloprotection, butresulted in increased overallsurvival (from 12.8 months in thechemotherapy-only group to20.1 months in the concurrenttrilaciclib and chemotherapygroup and 17.8 months in trilaciclibbefore chemotherapy group)

(^162

)

The most common adverse events wereneutropenia, thrombocytopenia,and anemia (

162

)

...............................................................................................................................................................................................................................................................................................................................................................................................................................................

RESEARCH | REVIEW