Verzenios® ▼ (abemaciklib): Patientrapporterade resultat

Detailed Information

Patient-reported outcomes were measured using paper versions of 4 self-administered questionnaires across MONARCH 3 and MONARCH 2.¹ The questionnaires are summarized in Table 1.

The analysis for each scale included all treated patients who completed the baseline assessment followed by at least 1 postbaseline assessment. The reason and number of missing or incomplete questionnaires were collected and summarized for each study.¹

Table 1. Patient-Reported Outcomes Questionnaires Administered in MONARCH 3 and MONARCH 2¹

Abbreviation	Definition	Description	MONARCH 3	MONARCH 2
mBPI-sf	Modified Brief Pain Inventory – short form	Pain intensity and pain assessment	NA	X
EORTC-QLQ-C30	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30	Health-related quality of life for general cancer	X	X
EORTC-QLQ-BR23	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast 23	Health-related quality of life for breast cancer	X	X
EQ-5D-5L	EuroQol 5-Dimension 5 Level	Self-reported health status	X	X

Abbreviation: NA = not applicable.

Phase 3 Study of Anastrozole or Letrozole Plus Abemaciclib or Placebo in MBC (MONARCH 3)

MONARCH 3 was a randomized, double-blind, placebo-controlled, phase 3 study of abemaciclib or placebo with an NSAI (anastrozole or letrozole) in 493 postmenopausal women with HR+, HER2- advanced or MBC with no prior systemic treatment in this setting.²

Patient-reported outcomes were collected at

• baseline

• every second cycle starting with cycle 2 through 19

• every third cycle after cycle 19, and

• short-term post-discontinuation follow-up.^2,3

Patient compliance rate for scheduled PROs was high and balanced between treatment arms with completion rates of

• ≥96% at baseline

• ≥88% for the duration of abemaciclib treatment, and

• ≥70% at follow-up.³

The most common reason for noncompletion during treatment was "study site failed to administer."³

The prespecified threshold for clinical meaningfulness was set at a difference of ≥10 points on a 0 to 100 scale. Patient-reported outcome scores for diarrhea in the abemaciclib arm showed a clinically (18.68 points) and statistically significant (p<.001) increase. However, diarrhea scores returned to near-baseline levels post therapy.³

Statistically, but not clinically, significant differences were seen in

• fatigue (4.96 ± 1.72; p=.004)

• systemic therapy side effects (4.48 ± 1.20; p<.001)

• appetite loss (4.03 ± 1.89; p=.03), and

• nausea/vomiting (2.77 ± 1.12; p=.01).³

Differences deemed to be clinically meaningful in terms of global health status or functional scores were not observed. These results were consistent with the investigator-reported TEAEs.³

Phase 3 Study of Fulvestrant With or Without Abemaciclib in MBC (MONARCH 2)

MONARCH 2 was a randomized, double-blind, placebo-controlled, phase 3 trial of abemaciclib or placebo plus fulvestrant in 669 women with HR+, HER2- advanced breast cancer with disease progression following ET.⁴

Patient-reported outcomes were assessed at

• baseline

• cycle 2

• every second cycle starting with cycle 3 through 13

• every third cycle after cycle 13, and

• once 30 days postdiscontinuation.⁵

Patient compliance rate for PROs was high and balanced between treatment arms with completion rates

• ≥95% at baseline

• ≥85% on-therapy, and 

• ≥77% at follow-up.⁵

The most common reason for noncompletion throughout treatment was “study site failed to administer questionnaire.”⁵

A prespecified analysis of time to worsening of pain, indicated by ≥2 point increase of “worst pain” or ≥1 level increase of WHO analgesic class, showed a numerically but not statistically significant benefit for abemaciclib plus fulvestrant compared with placebo plus fulvestrant (16.8 vs 11.9 months; HR=0.900; p=.400), based on mBPI-sf data.⁵

Most of the symptom and function scores (EORTC QLQ-C30 and EORTC-BR23) and mBPI-sf were stable and similar between the 2 treatment arms during the on-therapy and short-term follow-up study periods with no observed statistical or clinical significance. Four outcomes statistically (p<.001) favored the placebo plus fulvestrant arm over time including

• appetite loss

• nausea and/or vomiting

• diarrhea, and

• systemic therapy side effects.⁵

The diarrhea score was the only clinically meaningful (>10 points on a 100 scale) difference in the abemaciclib plus fulvestrant arm.⁵

These health-related QoL results are consistent with the previously disclosed safety profile. For all symptoms, the burden was reported during early study visits and returned to baseline or near-baseline levels for most patients.⁵

References

1. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646. https://doi.org/10.1200/jco.2017.75.6155

3. Goetz MP, Martin M, Tokunaga E, et al. Health-related quality of life in MONARCH 3: abemaciclib plus an aromatase inhibitor as initial therapy in HR+, HER2- advanced breast cancer. Oncologist. 2020;25(9):e1346-e1354. https://doi.org/10.1634/theoncologist.2020-0084

4. Sledge GW, 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(25):2875-2884. http://dx.doi.org/10.1200/JCO.2017.73.7585

5. Kaufman PA, Toi M, Neven P, et al. Health-related quality of life in MONARCH 2: abemaciclib plus fulvestrant in hormone receptor-positive, HER2-negative advanced breast cancer after endocrine therapy. Oncologist. 2020;25(2):e243-e251. https://doi.org/10.1634/theoncologist.2019-0551

Glossary

EORTC = European Organisation for Research and Treatment of Cancer

EORTC QLQ-BR23 = European Organisation for Research and Treatment of Cancer quality of life questionnaire – Breast 23

EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer quality-of-life questionnaire

ET = endocrine therapy

HER2- = human epidermal growth factor receptor 2-negative

HR = hazard ratio

HR+ = hormone receptor-positive

MBC = metastatic breast cancer

mBPI-sf = Modified Brief Pain Inventory – short form

NSAI = nonsteroidal aromatase inhibitor

PD = progressive disease

PR = partial response

PRO = patient-reported outcome

QoL = quality of life

SD = stable disease

TEAE = treatment-emergent adverse event

WHO = World Health Organization

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.