Skip to main content
Top

04-05-2024 | Everolimus | Research

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: a real-world evidence cohort

Authors: Rodrigo Sánchez-Bayona, Alfonso Lopez de Sa, Yolanda Jerez Gilarranz, Ana Sanchez de Torre, Manuel Alva, Isabel Echavarria, Fernando Moreno, Pablo Tolosa, Blanca Herrero Lopez, Alicia de Luna, Laura Lema, Salvador Gamez Casado, Ainhoa Madariaga, Sara López-Tarruella, Luis Manso, Coralia Bueno-Muiño, Jose A. Garcia-Saenz, Eva Ciruelos, Miguel Martin

Published in: Breast Cancer Research and Treatment

Login to get access

Abstract

Purpose

Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(−) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4–6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce.

Methods

A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan–Meier method were used for survival estimates.

Results

One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1–56 months). The median age at diagnosis was 49 years (range: 35–90 years). The estimated mPFS was 6.0 months (95%CI 5.3–7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6–11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8–10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9–8.4 months).

Conclusion

This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.
Literature
1.
go back to reference Malmgren JA, Mayer M, Atwood MK et al (2018) Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990–2010. Breast Cancer Res Treat 167(2):579–590CrossRefPubMed Malmgren JA, Mayer M, Atwood MK et al (2018) Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990–2010. Breast Cancer Res Treat 167(2):579–590CrossRefPubMed
2.
go back to reference Pan H, Gray R, Braybrooke J et al (2017) 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377(19):1836–1846CrossRefPubMedPubMedCentral Pan H, Gray R, Braybrooke J et al (2017) 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377(19):1836–1846CrossRefPubMedPubMedCentral
3.
go back to reference Gennari A, André F, Barrios CH, Cortés J, de Azambuja E, DeMichele A, Dent R, Fenlon D, Gligorov J, Hurvitz SA, Im SA, Krug D, Kunz WG, Loi S, Penault-Llorca F, Ricke J, Robson M, Rugo HS, Saura C, Schmid P, Singer CF, Spanic T, Tolaney SM, Turner NC, Curigliano G, Loibl S, Paluch-Shimon S, Harbeck N, ESMO Guidelines Committee (2021) ESMO clinical practice guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol 32(12):1475–1495. https://doi.org/10.1016/j.annonc.2021.09.019CrossRefPubMed Gennari A, André F, Barrios CH, Cortés J, de Azambuja E, DeMichele A, Dent R, Fenlon D, Gligorov J, Hurvitz SA, Im SA, Krug D, Kunz WG, Loi S, Penault-Llorca F, Ricke J, Robson M, Rugo HS, Saura C, Schmid P, Singer CF, Spanic T, Tolaney SM, Turner NC, Curigliano G, Loibl S, Paluch-Shimon S, Harbeck N, ESMO Guidelines Committee (2021) ESMO clinical practice guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol 32(12):1475–1495. https://​doi.​org/​10.​1016/​j.​annonc.​2021.​09.​019CrossRefPubMed
4.
go back to reference Turner NC, Ro J, André F et al (2015) Palbociclib in hormone-receptor- positive advanced breast cancer. N Engl J Med 373(3):209–219CrossRefPubMed Turner NC, Ro J, André F et al (2015) Palbociclib in hormone-receptor- positive advanced breast cancer. N Engl J Med 373(3):209–219CrossRefPubMed
5.
go back to reference Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O’Shaughnessy J (2022) Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med 386(10):942–950. https://doi.org/10.1056/NEJMoa2114663CrossRefPubMed Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O’Shaughnessy J (2022) Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med 386(10):942–950. https://​doi.​org/​10.​1056/​NEJMoa2114663CrossRefPubMed
6.
go back to reference Goetz MP, Toi M, Campone M et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 35(32):3638–3646CrossRefPubMed Goetz MP, Toi M, Campone M et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 35(32):3638–3646CrossRefPubMed
10.
go back to reference Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529. https://doi.org/10.1056/NEJMoa1109653CrossRefPubMed Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529. https://​doi.​org/​10.​1056/​NEJMoa1109653CrossRefPubMed
11.
go back to reference Kornblum N, Zhao F, Manola J, Klein P, Ramaswamy B, Brufsky A et al (2018) Randomized phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy: results of PrE0102. J Clin Oncol 36(16):1556–1563. https://doi.org/10.1200/JCO.2017.76.9331CrossRefPubMedPubMedCentral Kornblum N, Zhao F, Manola J, Klein P, Ramaswamy B, Brufsky A et al (2018) Randomized phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy: results of PrE0102. J Clin Oncol 36(16):1556–1563. https://​doi.​org/​10.​1200/​JCO.​2017.​76.​9331CrossRefPubMedPubMedCentral
14.
go back to reference Kalinsky K, Accordino MK, Chiuzan C, Mundi PS, Sakach E, Sathe C et al (2023) Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN Trial. J Clin Oncol 41(24):4004–4013. https://doi.org/10.1200/JCO.22.02392CrossRefPubMed Kalinsky K, Accordino MK, Chiuzan C, Mundi PS, Sakach E, Sathe C et al (2023) Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN Trial. J Clin Oncol 41(24):4004–4013. https://​doi.​org/​10.​1200/​JCO.​22.​02392CrossRefPubMed
15.
go back to reference Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F et al (2022) Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol 40(28):3246–3256. https://doi.org/10.1200/JCO.22.00338CrossRefPubMedPubMedCentral Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F et al (2022) Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol 40(28):3246–3256. https://​doi.​org/​10.​1200/​JCO.​22.​00338CrossRefPubMedPubMedCentral
16.
go back to reference Oliveira M, Pominchuk D, Nowecki Z, Hamilton E, Kulyaba Y, Andabekov T et al (2023) GS3-02 camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: results of the randomized, multi-dose phase 2 SERENA-2 trial. Cancer Res 83(5):GS3-02. https://doi.org/10.1158/1538-7445.SABCS22-GS3-02CrossRef Oliveira M, Pominchuk D, Nowecki Z, Hamilton E, Kulyaba Y, Andabekov T et al (2023) GS3-02 camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: results of the randomized, multi-dose phase 2 SERENA-2 trial. Cancer Res 83(5):GS3-02. https://​doi.​org/​10.​1158/​1538-7445.​SABCS22-GS3-02CrossRef
17.
go back to reference Dhakal A, Antony Thomas R, Levine EG et al (2020) Outcome of everolimus- based therapy in hormone-receptor-positive metastatic breast cancer patients after progression on palbociclib. Breast Cancer (Auckl) 14:1178223420944864PubMed Dhakal A, Antony Thomas R, Levine EG et al (2020) Outcome of everolimus- based therapy in hormone-receptor-positive metastatic breast cancer patients after progression on palbociclib. Breast Cancer (Auckl) 14:1178223420944864PubMed
22.
go back to reference Turner NC, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez Moreno HL, Hu X, Jhaveri K, Krivorotko P, Loibl S, Morales Murillo S, Okera M, Park YH, Sohn J, Toi M, Tokunaga E, Yousef S, Zhukova L, de Bruin EC, Grinsted L, Schiavon G, Foxley A, Rugo HS, CAPItello-291 Study Group (2023) Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med 388(22):2058–2070. https://doi.org/10.1056/NEJMoa2214131CrossRefPubMed Turner NC, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez Moreno HL, Hu X, Jhaveri K, Krivorotko P, Loibl S, Morales Murillo S, Okera M, Park YH, Sohn J, Toi M, Tokunaga E, Yousef S, Zhukova L, de Bruin EC, Grinsted L, Schiavon G, Foxley A, Rugo HS, CAPItello-291 Study Group (2023) Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med 388(22):2058–2070. https://​doi.​org/​10.​1056/​NEJMoa2214131CrossRefPubMed
24.
go back to reference André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D, SOLAR-1 Study Group (2019) Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 380(20):1929–1940. https://doi.org/10.1056/NEJMoa1813904CrossRefPubMed André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D, SOLAR-1 Study Group (2019) Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 380(20):1929–1940. https://​doi.​org/​10.​1056/​NEJMoa1813904CrossRefPubMed
25.
go back to reference Lawson M, Cureton N, Ros S, Cheraghchi-Bashi-Astaneh A, Urosevic J, D’Arcy S, Delpuech O, DuPont M, Fisher DI, Gangl ET, Lewis H, Trueman D, Wali N, Williamson SC, Moss J, Montaudon E, Derrien H, Marangoni E, Miragaia RJ, Gagrica S, Morentin Gutierrez P, Moss T, Maglennon GA, Sutton D, Polanski R, Rosen A, Cairns J, Zhang P, Sánchez-Guixé M, Serra V, Critchlow SE, Scott JS, Lindemann JPO, Barry ST, Klinowska T, Morrow CJ, Carnevalli LS (2023) The next-generation oral selective estrogen receptor degrader camizestrant (AZD9833) suppresses ER+ breast cancer growth and overcomes endocrine and CDK4/6 inhibitor resistance. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-23-0694CrossRefPubMedPubMedCentral Lawson M, Cureton N, Ros S, Cheraghchi-Bashi-Astaneh A, Urosevic J, D’Arcy S, Delpuech O, DuPont M, Fisher DI, Gangl ET, Lewis H, Trueman D, Wali N, Williamson SC, Moss J, Montaudon E, Derrien H, Marangoni E, Miragaia RJ, Gagrica S, Morentin Gutierrez P, Moss T, Maglennon GA, Sutton D, Polanski R, Rosen A, Cairns J, Zhang P, Sánchez-Guixé M, Serra V, Critchlow SE, Scott JS, Lindemann JPO, Barry ST, Klinowska T, Morrow CJ, Carnevalli LS (2023) The next-generation oral selective estrogen receptor degrader camizestrant (AZD9833) suppresses ER+ breast cancer growth and overcomes endocrine and CDK4/6 inhibitor resistance. Cancer Res. https://​doi.​org/​10.​1158/​0008-5472.​CAN-23-0694CrossRefPubMedPubMedCentral
27.
go back to reference Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J (2020) Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol 31(11):1526–1535. https://doi.org/10.1016/j.annonc.2020.08.2098CrossRefPubMed Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J (2020) Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol 31(11):1526–1535. https://​doi.​org/​10.​1016/​j.​annonc.​2020.​08.​2098CrossRefPubMed
29.
go back to reference Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G et al (2012) Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol 30(22):2718–2724. https://doi.org/10.1200/JCO.2011.39.0708CrossRefPubMed Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G et al (2012) Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol 30(22):2718–2724. https://​doi.​org/​10.​1200/​JCO.​2011.​39.​0708CrossRefPubMed
31.
32.
go back to reference Dowsett M, Kilburn L, Rimawi MF, Osborne CK, Pogue-Geile K, Liu Y, Jacobs SA, Finnigan M, Puhalla S, Dodson A, Martins V, Cheang M, Perry S, Holcombe C, Turner N, Swift C, Bliss JM, Johnston S, PALLET trialists (2022) Biomarkers of response and resistance to palbociclib plus letrozole in patients with ER+/HER2− breast cancer. Clin Cancer Res 28(1):163–174. https://doi.org/10.1158/1078-0432.CCR-21-1628CrossRefPubMed Dowsett M, Kilburn L, Rimawi MF, Osborne CK, Pogue-Geile K, Liu Y, Jacobs SA, Finnigan M, Puhalla S, Dodson A, Martins V, Cheang M, Perry S, Holcombe C, Turner N, Swift C, Bliss JM, Johnston S, PALLET trialists (2022) Biomarkers of response and resistance to palbociclib plus letrozole in patients with ER+/HER2− breast cancer. Clin Cancer Res 28(1):163–174. https://​doi.​org/​10.​1158/​1078-0432.​CCR-21-1628CrossRefPubMed
35.
go back to reference Jhaveri KL, Im SA, Saura C, Juric D, Loibl S, Kalinsky K, et al (2023) Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis. Presented at SABCS 2023. December 5–9, 2023. San Antonio, TX. Abstract GS03-13 Jhaveri KL, Im SA, Saura C, Juric D, Loibl S, Kalinsky K, et al (2023) Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis. Presented at SABCS 2023. December 5–9, 2023. San Antonio, TX. Abstract GS03-13
36.
go back to reference Turner N, Huang-Bartlett C, Kalinsky K, Cristofanilli M, Bianchini G, Chia S, Iwata H, Janni W, Ma CX, Mayer EL, Park YH, Fox S, Liu X, McClain S, Bidard FC (2023) Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol 19(8):559–573. https://doi.org/10.2217/fon-2022-1196CrossRefPubMed Turner N, Huang-Bartlett C, Kalinsky K, Cristofanilli M, Bianchini G, Chia S, Iwata H, Janni W, Ma CX, Mayer EL, Park YH, Fox S, Liu X, McClain S, Bidard FC (2023) Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol 19(8):559–573. https://​doi.​org/​10.​2217/​fon-2022-1196CrossRefPubMed
38.
go back to reference Lüftner D, Hartkopf AD, Lux MP, Overkamp F, Tesch H, Titzmann A, Pöschke P, Wallwiener M, Müller V, Beckmann MW, Belleville E, Janni W, Fehm TN, Kolberg HC, Ettl J, Wallwiener D, Schneeweiss A, Brucker SY, Fasching PA (2021) Challenges and opportunities for real-world evidence in metastatic luminal breast cancer. Breast Care (Basel). 16(2):108–114. https://doi.org/10.1159/000515701CrossRefPubMedPubMedCentral Lüftner D, Hartkopf AD, Lux MP, Overkamp F, Tesch H, Titzmann A, Pöschke P, Wallwiener M, Müller V, Beckmann MW, Belleville E, Janni W, Fehm TN, Kolberg HC, Ettl J, Wallwiener D, Schneeweiss A, Brucker SY, Fasching PA (2021) Challenges and opportunities for real-world evidence in metastatic luminal breast cancer. Breast Care (Basel). 16(2):108–114. https://​doi.​org/​10.​1159/​000515701CrossRefPubMedPubMedCentral
Metadata
Title
Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: a real-world evidence cohort
Authors
Rodrigo Sánchez-Bayona
Alfonso Lopez de Sa
Yolanda Jerez Gilarranz
Ana Sanchez de Torre
Manuel Alva
Isabel Echavarria
Fernando Moreno
Pablo Tolosa
Blanca Herrero Lopez
Alicia de Luna
Laura Lema
Salvador Gamez Casado
Ainhoa Madariaga
Sara López-Tarruella
Luis Manso
Coralia Bueno-Muiño
Jose A. Garcia-Saenz
Eva Ciruelos
Miguel Martin
Publication date
04-05-2024
Publisher
Springer US
Published in
Breast Cancer Research and Treatment
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-024-07324-8
Live Webinar | 01-10-2024 | 12:30 (CEST)

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live: Tuesday 1st October 2024, 12:30-14:00 (CEST)

In this live webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts will discuss the very latest data on the safety, efficacy and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL, as presented at ASH 2023, EU CAR-T 2024, and EHA 2024. 

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by: Novartis Pharma AG

Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare