Live introduction (ID 256)
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.
94MO - Quality of life (QoL) with fulvestrant (FUL)/palbociclib (PAL) versus FUL/placebo (PBO) in postmenopausal women with hormone receptor (HR)+/HER2- endocrine sensitive advanced breast cancer (ABC): results from GEICAM/2014-12 (FLIPPER) study (ID 258)
Abstract
Background
In the FLIPPER trial, FUL/PAL significantly improved progression-free survival (PFS) compared to FUL/PBO as first-line in patients (pts) with HR+/HER2- endocrine sensitive ABC. Here we present patient-reported outcome (PRO) results including health-related QoL (HRQoL).
Methods
Pts were randomized (1:1); 94 FUL/PAL, 95 FUL/PBO. PROs were evaluated at baseline (BL), every three cycles and at end of treatment using the EORTC QLQ-C30 and QLQ-BR23 questionnaires; 178 pts (94.2%) completed BL and ≥1 post-BL PROs. For functional and global health status (GHS)/QoL scales, higher scores represent better level of functioning or QoL and for symptom scales, worse symptoms. Time to deterioration (TTD) in GHS/QoL score considered ≥ 10points. Changes from BL and TTD were analysed using linear mixed-effect and Cox regression models, respectively.
Results
Questionnaire completion rates were high (>95%) for the first 22 cycles. BL scores were comparable between the two treatment arms. Significant between-arm differences were observed in overall change from BL of GHS/QoL, appetite loss, constipation and systemic therapy side effect scores favouring FUL/PBO. No other statistically significant differences were found between arms for the remaining functional and symptom scales. Median TTD in GHS/QoL was delayed in FUL/PBOL [30.3 months (mo)] vs. FUL/PAL (11.1 mo) [adjusted HR (aHR) 1.57, 95% CI 1.03-2.39, p=0.036]; TTD in GHS/QoL was delayed in PBO-treated pts without progressive disease (PD) (aHR 2.0, 95% CI 1.1-3.8, p=0.023) but not in pts with PD (aHR 1.2, 95% CI 0.6-2.2, p=0.658). No statistically significant differences in TTD were found for the other QLQ-C30 and QLQ-BR23 scales.
Conclusions
The TTD in GHS/QoL was prolonged with FUL/PBO, however, GHS/QoL was improved numerically in both arms. The overall HRQoL differences favouring FUL/PBO were clinically meaningful only for appetite loss. These results together with the improvement of PFS observed with FUL/PAL make of this a beneficial therapeutic option for these patients.
Clinical trial identification
NCT02690480.
Legal entity responsible for the study
GEICAM Breast Cancer Group.
Funding
GEICAM Spanish Breast Cancer Group.
Disclosure
A. Tibau: Honoraria (institution): Roche. M. Ramos: Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Novartis; Honoraria (institution): Roche. L. de la Cruz-Merino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD-Merck; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers-Squibb; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Celgene. A. Santaballa: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Research grant/Funding (institution): Pfizer. N. Martinez-Jañez: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Eisai. F. Moreno: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca. I. Fernandez-Perez: Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (institution): Pfizer; Honoraria (institution): Novartis; Honoraria (institution): Clovis. J. Alarcón: Honoraria (institution), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK; Honoraria (institution), Speaker Bureau/Expert testimony: Clovis; Honoraria (institution), Speaker Bureau/Expert testimony: Roche; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (institution), Advisory/Consultancy: MSD. J. de la Haba-Rodríguez: Honoraria (institution): AstraZeneca; Honoraria (institution): Pfizer; Honoraria (institution): Novartis; Honoraria (institution): Lilly. C. Bueno: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: Pfizer. J. Albanell: Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo. All other authors have declared no conflicts of interest.
Invited Discussant 93MO and 94MO (ID 259)
Q&A and live discussion (ID 260)
LBA3 - Atezolizumab with carboplatin as immune induction in metastatic lobular breast cancer: first results of the GELATO-trial (ID 320)
Abstract
Background
Invasive lobular breast cancer (ILC) is a special histological breast cancer subtype for which endocrine treatment is effective, but options thereafter are limited. ILC appears to be a different disease entity than invasive breast cancer of no special type. Translational data suggested that a subgroup of ILC has high expression of immune-related genes. Preclinical data revealed that this subtype may be responsive to combined platinum and immune checkpoint blockade. Here we present the first results of a single-arm phase II trial of atezolizumab (atezo) after immune induction with carboplatin in metastatic (m)ILC.
Methods
In the single-arm, multicenter GELATO-trial (NCT03147040), patients with mILC were treated with 12 cycles of carboplatin q1w (AUC 1.5 mg/mL·min) and atezo (1200 mg) q3w starting from the third cycle of carboplatin and continuing until progression or intolerability. Patients had received a maximum of 2 lines of palliative chemotherapy and were endocrine refractory in case of ER-positive tumors. The primary endpoint was progression-free survival at 24 weeks according to RECIST1.1. Following a Simon’s two-stage design, 22 patients, receiving at least 1 cycle of atezo, needed to be included in the first stage, of whom at least 3 patients had to be free of progression after 24 weeks to warrant further investigation in the second stage.
Results
Among 23 included evaluable patients, 4 patients were free of progression at 24 weeks, meeting the primary endpoint of the first stage of the trial. 1 patient has an ongoing response and 2 patients have started treatment but have not yet reached an endpoint. 4 out of these 21 patients had a partial response resulting in an objective response rate of 19% and 2 patients had stable disease, resulting in a clinical benefit rate of 29%. 4 of the patients with clinical benefit had triple negative (TN)-ILC, whereas in total 5 out of 23 patients had TN-ILC. Stromal tumor-infiltrating lymphocytes were not associated with clinical benefit. PD-L1 and CD8 will be presented at the meeting.
Conclusions
This is the first clinical immunotherapy trial executed exclusively in mILC. We show a clear efficacy signal of PDL1-blockade in combination with carboplatin in mILC, mainly in patients with TN-ILC.
Clinical trial identification
NCT03147040.
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Roche.
Disclosure
H. Horlings: Advisory/Consultancy: SlideScore.com; Advisory/Consultancy: Ellogen.ai. R.F. Salgado: Research grant/Funding (institution): Breast Cancer Research Foundation. G.S. Sonke: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche. K. de Visser: Research grant/Funding (institution): Roche; Advisory/Consultancy: Third Rock Ventures. T.N. Schumacher: Advisory/Consultancy: Adaptive Biotechnologies; Advisory/Consultancy, Shareholder/Stockholder/Stock options: AIMM Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Allogene Therapeutics; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merus; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Neon Therapeutics; Advisory/Consultancy: Scenic Biotech; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol-Myers-Squibb; Research grant/Funding (institution): Merck KGaA. C.U. Blank: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers-Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy: GSK; Advisory/Consultancy: GenMab; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Third Rock Venture; Research grant/Funding (institution): NanoString Technologies; Shareholder/Stockholder/Stock options: Immagene B.V. C.P. Schroder: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): SNS Oncology; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Synthon; Research grant/Funding (institution): CytoMx Therapeutics. V. Tjan-Heijnen: Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Honoraria (institution), Research grant/Funding (institution): E. Lilly. S.C. Linn: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eurocept- Pharmaceuticals; Advisory/Consultancy: Cergentis; Advisory/Consultancy: IBM; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Immunomedics. M. Kok: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers-Squib; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): AstraZeneca.