Experts present data
Quality of life with ribociclib plus aromatase inhibitor vs abemaciclib plus aromatase inhibitor as first-line treatment of HR+/HER2− advanced breast cancer, assessed via matching-adjusted indirect comparison (MAIC)
Rugo HS, O'Shaughnessy J, Jhaveri K, et al.
Background and methods1-3
- KISQALI and abemaciclib are known to have differences in safety profiles related to differences in target inhibition
- Many AEs, even mild, can significantly impact QoL; thus, patient-reported outcomes can help inform treatment decisions
- An anchored MAIC of QoL in MONARCH-3 and MONALEESA-2 was performed for KISQALI + AI vs abemaciclib + AI
- While cross-trial comparisons have inherent limitations due to differences in study designs and patient populations, MAIC helps to correct for some of these differences, unlike an unadjusted indirect comparison
Results1
KISQALI + AI was numerically favored over abemaciclib + AI for time to sustained deterioration (TTSD) in multiple functional domains
KISQALI + AI was associated with better symptom-related QoL vs abemaciclib + AI
TTSD analysis significantly favored KISQALI + AI in 4 symptom scales: appetite loss, diarrhea, fatigue, and arm symptoms
Abemaciclib was not significantly favored over KISQALI in any functional or symptom scale.
See QoL data with KISQALI across 3 phase III clinical trials
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KISQALI + ET demonstrated significant PFS benefit following progression on CDK4/6 inhibitor + ET
A randomized phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or metastatic hormone receptor positive, HER2 negative breast cancer: MAINTAIN trial
Kalinsky K, Accordino MK, Chiuzan C, et al.
Background and methods4
- The efficacy of fulvestrant or exemestane with or without KISQALI was evaluated in a randomized phase II trial in patients whose cancer previously progressed on any CDK4/6 inhibitor + any ET in HR+/HER2– mBC
- The majority of patients (87%) received prior palbociclib, while 12% received prior KISQALI
Results4
KISQALI + ET significantly improved median PFS by 2.5 months, with more than a 40% decrease in risk of progression or death
- KISQALI demonstrated improved clinical benefit rate over placebo (43% vs 25%)
- This is the first trial to show an efficacy benefit with KISQALI and switching endocrine therapy after progression on a CDK4/6 inhibitor + ET
View significant OS data for KISQALI
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Matching adjusted indirect comparison of PFS & OS comparing ribociclib + letrozole vs palbociclib + letrozole as first-line treatment of HR+/HER2− ABC: Analysis based on updated PFS & final OS results of MONALEESA-2 & PALOMA-2
Jhaveri K, O’Shaughnessy J, Fasching PA, et al.
Background and methods5
- Currently, there are no head-to-head studies of CDK4/6 inhibitors in the treatment of HR+/HER2− advanced breast cancer
- An anchored MAIC of PFS and OS in MONALEESA-2 and PALOMA-2 was performed to estimate relative effectiveness of 1L KISQALI + letrozole vs 1L palbociclib + letrozole
MATCHED AND UNMATCHED BASELINE PATIENT AND DISEASE CHARACTERISTICS
Some MONALEESA-2 ITT patients were removed to match PALOMA-2 reported baseline data categories.
PALOMA-2 used “disease-free interval” (DFI) to refer to TFI, defined as time from end of (neo)adjuvant treatment to recurrence.
Results5
- No significant difference in PFS: HR was 0.80 (95% CI: 0.58-1.11; P=0.187) for KISQALI + letrozole vs palbociclib + letrozole
- OS significantly favored KISQALI + letrozole over palbociclib + letrozole: HR was 0.68 (95% CI: 0.48-0.96; P=0.031) for KISQALI + letrozole vs palbociclib + letrozole
- While MAIC analyses provide an estimate for differences between 2 trials in the absence of head-to-head clinical studies, they do not serve as a replacement for a clinical trial to confirm or refute a true difference
View significant OS data for KISQALI
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Primary results from the randomized phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2− advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy.
Lu YS, Mahidin EIBM, Azim H, et al.
Background and methods6
- Combination chemotherapy has traditionally been used for urgent disease control in aggressive advanced breast cancer
- Aggressive disease features included symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic nonvisceral disease
- This is the first trial comparing a CDK4/6 inhibitor + ET vs combination chemotherapy in this patient population
- The randomized phase II RIGHT Choice trial investigated the efficacy and safety of first-line KISQALI + ET vs chemotherapy in pre/perimenopausal patients with aggressive HR+/HER2− advanced breast cancer
- Approximately half the patients were in visceral crisis (52.3%) and two-thirds had symptomatic visceral metastases (67.6%)
Results6
Statistically significant PFS benefit of ~1 year for KISQALI + ET vs combination chemotherapy
HR=0.54 (95% CI: 0.36-0.79; P=0.0007)
- OS data were immature at data cutoff
- The ORR was similar for KISQALI + ET vs chemotherapy (65.2% vs 60.0%)
- No new safety signals were observed in patients with KISQALI
- Lower rates of treatment-related serious AEs (1.8% vs 8.0%) and lower rates of discontinuation due to treatment-related AEs (7.1% vs 23.0%) were seen with KISQALI + ET vs chemotherapy
View significant OS data for KISQALI
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KISQALI + ET as first-line therapy enhances outcomes of subsequent therapy
Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer in the MONALEESA-2, -3, and -7 studies
Hamilton E, Spring L, Fasching PA, et al.
Background and methods7
- Significant OS and PFS benefit were shown with 1L KISQALI + ET in patients with pre/peri and postmenopausal advanced breast cancer in the MONALEESA trials
- A pooled analysis of data from patients receiving 1L therapy in the MONALEESA trials evaluated subsequent therapy after progression
- Three groups of subsequent therapies were assessed: ET only, chemotherapy, and targeted therapy
Results7
Fewer patients in the KISQALI arm received subsequent chemotherapy compared with placebo
Regardless of the type of the first subsequent therapy, the durations of both the study treatment and the first subsequent therapy were generally longer for patients treated with KISQALI vs placebo
- Among patients on 1L KISQALI + ET, subsequent CDK4/6 inhibitor use was associated with the longest mOS (84 months [95% CI: 84-NE]), followed by ET only (60 months [95% CI: 51-68]), then a non–CDK4/6 inhibitor targeted therapy (52 months [95% CI: 43-72]); post-progression chemotherapy was associated with the shortest mOS (37 months [95% CI: 32-48])
- These findings confirm that upfront treatment with KISQALI does not worsen patient outcomes