Correlative analysis of overall survival by intrinsic subtype across the MONALEESA-2, -3, and -7 studies of ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer
Carey LA, Solovieff N, André F, et al.
Background and methods
- KISQALI + ET demonstrated a statistically significant PFS and OS benefit in 3 phase III clinical trials (MONALEESA-2, -3, and -7) in patients with HR+/HER2− advanced breast cancer1-6
- A pooled analysis of patients in the MONALEESA trials previously demonstrated a significant PFS benefit with KISQALI + ET vs placebo + ET in the luminal A (HR=0.63; P=0.0007), luminal B (HR=0.52; P<0.0001), and HER2E (HR=0.39; P<0.0001) subtypes7
- In order to evaluate the association of intrinsic subtype with OS, this retrospective exploratory analysis used tumor samples pooled from the MONALEESA-2, -3, and -7 trials8,9
- 997 tumor samples (71% primary) from patients enrolled in the MONALEESA-2 (n=318), -3 (n=414), and -7 (n=265) trials underwent subtyping
- Subtype distribution was consistent across treatment arms (KISQALI arm, n=585; placebo arm, n=412)
Subtype distribution in the pooled MONALEESA dataset8
- Luminal A: 54.4%
- Luminal B: 27.9%
- HER2E: 14.7%
- Basal-like: 3.0%
Results
KISQALI demonstrated a consistent OS benefit among the most common intrinsic subtypes9,10
- Intrinsic subtype was prognostic for and predictive of OS outcomes in both the KISQALI and placebo arms9
- The greatest relative reduction in risk of death was observed in the HER2E subtype, which is commonly associated with endocrine resistance and a very poor prognosis compared with luminal disease9
OVERALL SURVIVAL BY INTRINSIC SUBTYPE | KISQALI + ET9
- The only subtype in which an OS benefit was not observed was the basal-like subtype7,9
- The investigators warned the results should be interpreted with caution due to small sample size (3% in each arm)
- From a clinical and biological perspective, the basal-like subtype is more similar to triple-negative breast cancer than to HR+/HER2– breast cancer, including its association with poor outcomes
View expert perspectives on OS results among intrinsic subtypes in the MONALEESA trial program
See more in-depth information about intrinsic subtypes and the MONALEESA trials>
Download the presentation slides
PAM50 was the genetic microarray used in the pooled analysis to identify subtypes by analyzing the expression of 50 genes9,10
Click below to view recent findings for KISQALI in several areas
OS subgroup analysis by metastatic site in postmenopausal patients
KISQALI showed consistent OS benefit across subgroups, regardless of number of metastatic sites, baseline location, or prior (neo)adjuvant chemotherapy or endocrine therapy
Overall survival subgroup analysis by metastatic site from the phase 3 MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2− advanced breast cancer
O’Shaughnessy J, Stemmer S, Burris H, et al.
Background and methods
- The phase III, randomized, double-blind MONALEESA-2 trial recently reported a statistically significant overall survival benefit with first-line KISQALI + letrozole vs placebo + letrozole in postmenopausal patients with HR+/HER2– advanced breast cancer1,11
- A prespecified exploratory analysis of patient subgroups by location of metastases, number of metastatic sites, and prior therapy in the MONALEESA-2 trial demonstrated consistent overall survival benefits, as demonstrated below12
Results
- This analysis was exploratory and not powered for statistical significance12
- OS benefit in subgroups was consistent with that in the ITT population of the MONALEESA-2 trial13
- Consistent improvement in long-term survival at 5 and 6 years with KISQALI observed in all subgroups12
SUBGROUP ANALYSES BY METASTATIC SITE12
PFS and OS data from 2 subgroup analyses
De novo vs late relapse metastatic presentation was not prognostic for disease outcomes, while prior CT exposure was associated with poorer PFS and OS in the MONALEESA-3 trial
Analysis of first-line (1L) patients (pts) with de novo disease vs late relapse and all pts with vs without prior chemotherapy (CT) in the MONALEESA-3 (ML-3) trial
De Laurentiis M, Lambertini M, Chia S, et al.
Background and methods
- The phase III MONALEESA-3 trial demonstrated a significant OS benefit with KISQALI + fulvestrant vs placebo + fulvestrant as 1L or 2L therapy in postmenopausal patients with prior ET ([neo]adjuvant or ≤1 prior ET for aBC) and no CT for aBC14
- Prior treatment ([neo]adjuvant or advanced setting) may impact subsequent therapy outcomes, including OS15
- This analysis was conducted to better understand the potential effect of prior treatment on OS outcomes based on 2 subgroup analyses from the MONALEESA-3 trial15:
- 1L patients with de novo disease vs late relapse (those who relapsed >12 months from completion of [neo]adjuvant ET with no prior treatment for aBC)
- All patients who received prior (neo)adjuvant chemotherapy vs those without prior (neo)adjuvant chemotherapy
Results
KISQALI + FULVESTRANT DEMONSTRATED CONSISTENT PFS AND
OS BENEFITS ACROSS ALL SUBGROUPS OF THE ANALYSIS15
- Metastatic presentation (de novo vs late relapse) was not prognostic for disease outcomes; however, prior chemotherapy exposure, even in the (neo)adjuvant setting, was associated with poorer PFS and OS15
- The addition of KISQALI showed consistent PFS and OS benefit across all subgroups and a decrease in relative risk of death by 24% in patients with prior exposure to chemotherapy15
View significant postmenopausal OS with KISQALI + fulvestrant>
Pooled findings about the importance of QoL and its assessment in clinical practice
QoL discussions from 2 angles: differing views from HCPs compared with the patients they treat
Assessment of quality of life (QoL) in patients with advanced breast cancer (ABC) in clinical practice: a real-world multi-country survey
Cardoso F, Rihani J, Aubel D, et al.
Background and methods
- Patient quality of life is a key factor in the treatment of advanced breast cancer. This survey evaluated the importance of quality of life, its impact on treatment decisions, and how it is discussed in a clinical setting16
- Data from 277 oncologists, 225 oncology nurses, and 467 patients were collected from July 2020 to May 202116
Results
The survey found disparities in how QoL is assessed and discussed in real-world clinical practice.
- Asking about quality of life at follow-up appointments16:
- Most HCPs, 88% of oncologists and 96% of oncology nurses, reported doing so
-
Patients reported a lower frequency of these discussions (oncologists, 64%; oncology nurses, 43%)
- Reporting side effects16:
- 40% of patients who experienced a side effect agreed that they did not share the information because their HCP did not ask about it
- 28% of patients agreed that they did not report a side effect for fear of their oncologist changing their treatment
- “I have enough time to discuss quality of life with my patients”16:
- 81% of HCPs did not completely agree with the above statement
See QoL data with KISQALI across 3 phase III clinical trials>