Abstract 329P
Background
ET resistance is a challenge in the treatment of pts with ABC. RIB + ET demonstrated significant overall survival (OS) benefit vs. placebo (PBO) in postmenopausal (ML-3; hazard ratio [HR], 0.71; P = .00973; Slamon et al. N Engl J Med. 2020) and pre- and perimenopausal (ML-7; HR, 0.72; P = .00455; Im et al. N Engl J Med. 2019) pts with HR+/HER2− ABC. We report outcomes (including 6-mo progression-free survival [PFS] rate and OS) associated with RIB + ET in pts with ET-resistant disease in ML-3 and -7.
Methods
Pts in ML-3 (≤ 1 ET for ABC) were randomized 2:1 to RIB or PBO (both + fulvestrant). Pts in ML-7 (no prior ET for ABC) were randomized 1:1 to RIB or PBO (both + ET + goserelin; only pts treated with a nonsteroidal aromatase inhibitor were included in this analysis). ET resistance was defined as relapse within the first 2 y of (neo)adjuvant ET (in ML-3 and -7) or progressive disease within the first 6 mo of 1L ET for ABC while on ET (in ML-3). Efficacy in this patient subgroup was calculated with the 6-mo PFS rate and median PFS and OS to assess patterns of response to ET.
Results
In ML-3, 53 pts with RIB vs. 25 with PBO had ET resistance; in ML-7, 44 vs. 41 pts had ET resistance, respectively. Baseline characteristics of these pts were balanced between RIB and PBO arms in both trials. In ML-3, the 6-mo PFS rate was 67% vs. 46% with RIB vs. PBO. Median PFS among pts with ET resistance was 13.4 vs. 5.7 mo (HR, 0.62; 95% CI, 0.37-1.05); median OS was 37.5 vs. 31.7 mo (HR, 0.70; 95% CI, 0.37-1.33). In ML-7, the 6-mo PFS rate was 74% vs. 46% with RIB vs. PBO. Median PFS among pts with ET resistance was 14.5 vs. 5.6 mo (HR, 0.56; 95% CI, 0.34-0.92); median OS was not estimable vs. 32.7 mo (HR, 0.59; 95% CI, 0.30-1.14).
Conclusions
Among pts with ET resistance in ML-3 and -7, RIB demonstrated a greater estimated 6-mo PFS rate than PBO. Survival benefits were consistent with those in the overall study populations. In both trials, the median PFS in pts with ET resistance treated with RIB was more than twice as long compared with PBO. In ML-3 and -7, RIB treatment led to a 30% and 41% relative reduction in the risk of death in pts with ET resistance.
Clinical trial identification
NCT02422615 (September 19, 2018); NCT02278120 (February 26, 2019).
Editorial acknowledgement
Medical writing support was provided by William Ho, PhD, at MediTech Media, Ltd, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceutical Corporation.
Disclosure
S.A. Hurvitz: Research grant/Funding (institution), Research Grant: Ambryx; Research grant/Funding (institution), Research Grant: Amgen; Research grant/Funding (institution), Research Grant: Bayer; Research grant/Funding (institution), Research Grant: OBI Pharma; Research grant/Funding (institution), Research Grant: Bimarin; Research grant/Funding (institution), Research Grant: Cascadian; Research grant/Funding (institution), Research Grant: Daiichi Sankyo; Research grant/Funding (institution), Research Grant: Dignitana; Research grant/Funding (institution), Research Grant: Genentech; Research grant/Funding (institution), Research Grant: Glaxo-Smith Kline; Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Grant; Travel Support: Eli Lilly; Research grant/Funding (institution), Research Grant: Macrogenics; Research grant/Funding (institution), Research Grant: Medivation; Research grant/Funding (institution), Research Grant: Merrimack; Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Grant; Travel Support: Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Grant; Travel Support: OBI Pharma; Research grant/Funding (institution), Research Grant: Pfizer; Research grant/Funding (institution), Research Grant: Pieris; Research grant/Funding (institution), Research Grant: Puma; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: Seattle Genetics. S.C. Lee: Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: ACT Genomics; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Funding; Advisory Board/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Funding; Advisory Board/Consultancy; Travel Support: Pfizer; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Roche; Research grant/Funding (institution), Research Funding: Taiho Pharmaceutical; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Amgen. G. Jerusalem: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, Research Grant; Advisory Board/Consultancy; Non-Financial Support: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, Research Grant; Advisory Board/Consultancy; Non-Financial Support: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, Research Grant; Advisory Board/Consultancy; Non-Financial Support: Pfizer; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: Eli Lilly; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: Amgen; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: AstraZeneca; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: AbbVie; Non-remunerated activity/ies, Non-Financial Support: MedImmune; Non-remunerated activity/ies, Non-Financial Support: Merck. S-A. Im: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: MediPacto; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Eli Lilly; Research grant/Funding (institution), Research Grant: Daewoong. S.K.L. Chia: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Hoffman LaRoche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Eli Lilly. S. Campos: Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: Roche; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: MSD; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Advisory Board/Consultancy; Non-Financial Support: Bristol-Myers Squibb. G.S. Sonke: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Steering Committee Advisory: Novartis; Research grant/Funding (institution), Research Grant: Merck; Research grant/Funding (institution), Research Grant: AstraZeneca; Research grant/Funding (institution), Research Grant: Roche. A. Lteif: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. H. Hu: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. Y. Wang: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. K. Rodriguez-Lorenc: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. Y-S. Lu: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy; Clinical Trial Study Fee: Novartis; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: Merck Sharpe and Dohme; Research grant/Funding (institution), Research Grant: Pfizer; Speaker Bureau/Expert testimony, Speaker Bureau: Eisai.