Abstract P4-13-07: SEQUERPLUS: A multicenter real practice observational study investigating the endocrine-based (E) therapies sequential approach in hormonal receptor positive (HR+) HER2 negative (-) metastatic breast cancer (MBC)
Authors: Fabi A , Giannarelli D , Botticelli A , Scagnoli S , Pellegrino A , Fabbri A , Corsi D , Magri V , Pizzuti L , Paris I , Bruni V , Pace R , Lanzetta G , Stani S , Moscetti L , Marchetti P , Piesco G , Cognetti F , Rossi V 
Published: May 2019

Abstract
Background: Despite the sequential E therapy is recognized as the preferred approach for HR+/HER2- MBC, no data from clinical trials support the choice between the different sequential strategies.
Methods: In this retrospective study descriptive statistics are reported using the median (Interquartile range, IQR) or frequency. Progression Free Survival (PFS) curves were estimated with the Kaplan-Meier method and compared with the log-rank test. Analysis were performed by SPSS version 21.0 (SPSS Inc., Chicago, IL).
Results: From January 2006 to December 2017, 240 patients (pts) with HR+/HER2- MBC receiving at least two consecutive E therapies as first approach were selected from 12 italian cancer centers. The median age at the time of metastasis onset was 63.5 (IQR: 55-72.5) years; 184 (76.7%) pts were in menopausal status; 38 (16%) had de novo stage IV disease and the remaining 202 (84%) had recurrent BC with a median time of 78 months (5-396 months). At the beginning of MBC diagnosis, 148 (62%) pts had a single site of distant disease, 108 (45%) of whom had bone only disease and 45 (18.8%) presented visceral involvement too. The aromatase inhibitor (AI) was chosen as I-line therapy in 146 (60.9%) pts, followed by Fulvestrant (F) in 62 (25.8%) pts; the alternative I-line options were everolimus-exemestane (Eve-Exe), tamoxifene (T), Palbociclib (P)+AI and F+AI in 13 (5.4%), 14 (5.8%), 1 (0.4%) and 4 (1.7%) pts, respectively. The most favourite II-line option resulted F for 111 (46.2%) pts while the Eve-Exe combination was chosen in 70 (29.2%) pts, AI in 30 (12.5%) pts; T, AI+F, P+F and antiprogestincwere administered in 4 (1.7%), 4 (1.7%), 19 (7.9%) and 2 (0.8%) pts, respectively. For I and II-line, the AI followed by F (40%) and F followed by Eve-Exe (18%) were the most common sequential therapeutic approaches; the several alternative options were scanty used (in less than 10%). The median Progression-Free Survival (PFS) from first and second-line E therapies resulted 15.7 (95% CI 13.3-18.1) and 10.3 months (95% CI 8.7-11.9), respectively. Among 194 pts with disease progression after second-line E therapy, 87 (44.8%) received further E therapies with a median PFS 9.4 months (95% CI 7.9-10.9). The remaining 70 (29.2%) pts was treated with palliative chemotherapy. Interestingly, the median Overall Survival (OS) was even longer for pts receiving more lines of E therapies compared to the group with earlier introduction of chemotherapy (204.3 vs 92.8; p=0.007).
Finally, in the subgroup analyses a longer PFS benefit was observed in pts with disease recurrence over 12 months from initial diagnosis (38.1 vs 30.3 months p=0.04) and limited sites of disease involvement at the time of MBC diagnosis (37.6 vs 28.3 months, p=0.03)
Conclusions: The sequential use in first and second-line setting of E therapies for HR+/HER2- MBC improves median PFS up to 32.3 months. According to real practice experience the optimal sequences could be AIs followed by F and F followed by Eve-Exe. A role for these compounds should be redefined in the light of recently introduction of CDK 4/6 inhibitors in combination with AIs or F for the first or later lines.
Citation Format: Fabi A, Giannarelli D, Botticelli A, Scagnoli S, Pellegrino A, Fabbri A, Corsi D, Magri V, Pizzuti L, Paris I, Bruni V, Pace R, Lanzetta G, Stani S, Moscetti L, Marchetti P, Piesco G, Cognetti F, Rossi V. SEQUERPLUS: A multicenter real practice observational study investigating the endocrine-based (E) therapies sequential approach in hormonal receptor positive (HR+) HER2 negative (-) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-07.