Y. Lu (Taipei City, Taiwan)
Author Of 2 Presentations
Anti-angiogenesis therapy for breast cancer with brain or leptomeningeal mets (ID 13)
93MO - Overall survival (OS) results by age subgroup from the phase III MONALEESA-7 (ML-7) trial of premenopausal patients (pts) with HR+/HER2? advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB) (ID 257)
Abstract
Background
RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), significantly prolonged OS in pre- or perimenopausal pts with HR+/HER2− ABC in ML-7 with updated results (median, 58.7 vs 48.0 mo for RIB + ET vs placebo [PBO] + ET; HR, 0.76 [95% CI, 0.61-0.96]; NCT02278120). Younger pts with HR+/HER2− ABC tend to have a poorer prognosis. We conducted an exploratory analysis to characterize outcomes in pts <40 vs ≥40 y of age.
Methods
Pre- or perimenopausal pts with HR+/HER2− ABC with no prior CDK4/6i or ET for ABC were randomized 1:1 to receive RIB or PBO plus goserelin and a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen. OS and other efficacy endpoints were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods.
Results
The median follow-up time was 53.5 mo (data cutoff, 29 June 2020). In the RIB vs PBO arm, 98 vs 88 pts were <40 y and 237 vs 249 pts were ≥40 y. Median age (range) in RIB vs PBO was 35 y (25-39 y) vs 36 y (29-39 y) in pts <40 y, and 45 y (40-58 y) vs 46 y (40-58 y) in pts ≥40 y. In pts <40 y, RIB + ET demonstrated an OS benefit vs PBO + ET (median, 51.3 vs 40.5 mo; HR, 0.65; 95% CI, 0.43-0.98). RIB had a longer median OS vs PBO in pts ≥40 y (median, 58.8 vs 51.7 mo; HR, 0.81; 95% CI, 0.62-1.07). Similar trends were observed for OS in NSAI-treated pts and in all pts for PFS2, time to chemotherapy (CT), and CT-free survival (Table). In pts who discontinued, subsequent antineoplastic therapies were received by 77.3% vs 75.0% of pts age <40 y in RIB vs PBO arms, respectively, and 77.2% vs 79.2% of pts ≥40 y. Subsequent CDK4/6i were received in 16.0% vs 27.5% of pts age <40 y and 11.6% vs 25.7% of pts ≥40 y in RIB vs PBO arms. Adverse events were consistent with the known safety profile of ML-7. ITT, intent to treat; NR, not reached. aIn ITT.
Age <40 y Age ≥40 y RIB + ET PBO + ET RIB + ET PBO + ET OS in NSAI cohort n=78 n=66 n=170 n=181 Events, n (%) 36 (46.2) 39 (59.1) 71 (41.8) 81 (44.8) Median, mo 50.2 40.7 58.7 54.1 HR (95% CI) 0.66 (0.42-1.05) 0.85 (0.61-1.16) PFS2a n=98 n=88 n=237 n=249 Events, n (%) 54 (55.1) 60 (68.2) 123 (51.9) 161 (64.7) Median, mo 46.0 25.5 43.6 32.7 HR (95% CI) 0.59 (0.40-0.86) 0.71 (0.56-0.89) Time to first CTa n=98 n=88 n=237 n=249 Events, n (%) 40 (40.8) 43 (48.9) 104 (43.9) 130 (52.2) Median, mo NR 36.6 50.2 36.8 HR (95% CI) 0.65 (0.42-1.01) 0.69 (0.53-0.90) CT-free survivala n=98 n=88 n=237 n=249 Events, n (%) 53 (54.1) 63 (71.6) 137 (57.8) 173 (69.5) Median, mo 46.5 22.7 41.5 27.6 HR (95% CI) 0.58 (0.40-0.85) 0.68 (0.54-0.85)
Conclusions
In ML-7, RIB prolonged OS and improved post-progression outcomes in HR+/HER2− ABC, particularly in younger pts, who have a substantial unmet need.
Clinical trial identification
NCT02278120.
Editorial acknowledgement
This abstract was developed with editorial assistance provided by Chris Carter, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
Y-S. Lu: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Speaker Bureau/Expert testimony: Eisai. N.S. El Saghir: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. S.A. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Bimarin; Research grant/Funding (institution): Cascadian; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GSK; Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Seattle Genetics. D. Tripathy: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Polyphor; Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Leadership role: OncoPep; Advisory/Consultancy: Sellas Life Sciences Group. F. Cardoso: Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eisai; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GSK; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Prime; Honoraria (institution): Roche. M.A. Colleoni: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy: OBI Pharma; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Celldex. S. Campos-Gomez: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. C. Wang, Y. Wang, J.P. Zarate, A. Chakravartty: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S-A. Im: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MediPacto; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Daewoong. All other authors have declared no conflicts of interest.
Presenter Of 2 Presentations
Anti-angiogenesis therapy for breast cancer with brain or leptomeningeal mets (ID 13)
93MO - Overall survival (OS) results by age subgroup from the phase III MONALEESA-7 (ML-7) trial of premenopausal patients (pts) with HR+/HER2? advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB) (ID 257)
Abstract
Background
RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), significantly prolonged OS in pre- or perimenopausal pts with HR+/HER2− ABC in ML-7 with updated results (median, 58.7 vs 48.0 mo for RIB + ET vs placebo [PBO] + ET; HR, 0.76 [95% CI, 0.61-0.96]; NCT02278120). Younger pts with HR+/HER2− ABC tend to have a poorer prognosis. We conducted an exploratory analysis to characterize outcomes in pts <40 vs ≥40 y of age.
Methods
Pre- or perimenopausal pts with HR+/HER2− ABC with no prior CDK4/6i or ET for ABC were randomized 1:1 to receive RIB or PBO plus goserelin and a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen. OS and other efficacy endpoints were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods.
Results
The median follow-up time was 53.5 mo (data cutoff, 29 June 2020). In the RIB vs PBO arm, 98 vs 88 pts were <40 y and 237 vs 249 pts were ≥40 y. Median age (range) in RIB vs PBO was 35 y (25-39 y) vs 36 y (29-39 y) in pts <40 y, and 45 y (40-58 y) vs 46 y (40-58 y) in pts ≥40 y. In pts <40 y, RIB + ET demonstrated an OS benefit vs PBO + ET (median, 51.3 vs 40.5 mo; HR, 0.65; 95% CI, 0.43-0.98). RIB had a longer median OS vs PBO in pts ≥40 y (median, 58.8 vs 51.7 mo; HR, 0.81; 95% CI, 0.62-1.07). Similar trends were observed for OS in NSAI-treated pts and in all pts for PFS2, time to chemotherapy (CT), and CT-free survival (Table). In pts who discontinued, subsequent antineoplastic therapies were received by 77.3% vs 75.0% of pts age <40 y in RIB vs PBO arms, respectively, and 77.2% vs 79.2% of pts ≥40 y. Subsequent CDK4/6i were received in 16.0% vs 27.5% of pts age <40 y and 11.6% vs 25.7% of pts ≥40 y in RIB vs PBO arms. Adverse events were consistent with the known safety profile of ML-7. ITT, intent to treat; NR, not reached. aIn ITT.
Age <40 y Age ≥40 y RIB + ET PBO + ET RIB + ET PBO + ET OS in NSAI cohort n=78 n=66 n=170 n=181 Events, n (%) 36 (46.2) 39 (59.1) 71 (41.8) 81 (44.8) Median, mo 50.2 40.7 58.7 54.1 HR (95% CI) 0.66 (0.42-1.05) 0.85 (0.61-1.16) PFS2a n=98 n=88 n=237 n=249 Events, n (%) 54 (55.1) 60 (68.2) 123 (51.9) 161 (64.7) Median, mo 46.0 25.5 43.6 32.7 HR (95% CI) 0.59 (0.40-0.86) 0.71 (0.56-0.89) Time to first CTa n=98 n=88 n=237 n=249 Events, n (%) 40 (40.8) 43 (48.9) 104 (43.9) 130 (52.2) Median, mo NR 36.6 50.2 36.8 HR (95% CI) 0.65 (0.42-1.01) 0.69 (0.53-0.90) CT-free survivala n=98 n=88 n=237 n=249 Events, n (%) 53 (54.1) 63 (71.6) 137 (57.8) 173 (69.5) Median, mo 46.5 22.7 41.5 27.6 HR (95% CI) 0.58 (0.40-0.85) 0.68 (0.54-0.85)
Conclusions
In ML-7, RIB prolonged OS and improved post-progression outcomes in HR+/HER2− ABC, particularly in younger pts, who have a substantial unmet need.
Clinical trial identification
NCT02278120.
Editorial acknowledgement
This abstract was developed with editorial assistance provided by Chris Carter, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
Y-S. Lu: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Speaker Bureau/Expert testimony: Eisai. N.S. El Saghir: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. S.A. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Bimarin; Research grant/Funding (institution): Cascadian; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GSK; Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Seattle Genetics. D. Tripathy: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Polyphor; Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Leadership role: OncoPep; Advisory/Consultancy: Sellas Life Sciences Group. F. Cardoso: Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eisai; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GSK; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Prime; Honoraria (institution): Roche. M.A. Colleoni: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy: OBI Pharma; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Celldex. S. Campos-Gomez: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. C. Wang, Y. Wang, J.P. Zarate, A. Chakravartty: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S-A. Im: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MediPacto; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Daewoong. All other authors have declared no conflicts of interest.