Skip to main content
Erschienen in: Breast Cancer Research and Treatment 3/2020

27.07.2020 | Epidemiology

The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer

verfasst von: Sudpreeda Chainitikun, James P. Long, Ruben Rodriguez-Bautista, Toshiaki Iwase, Debu Tripathy, Takeo Fujii, Naoto T. Ueno

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2− metastatic breast cancer (MBC). When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. The purpose of this study was to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC.

Methods

We conducted a retrospective study of patients with HR+/HER2− MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999 to 2017. We collected baseline clinicopathological and all treatment data. Primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC.

Results

For the 1258 patients analyzed, mean age was 55.3 years (range 21–91). Previous treatment with targeted therapy was recorded for 390 patients (31%): 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 treated with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (28.6%). After adjustment for all factors in a multivariate model, previous treatment with a CDK4/6 inhibitor had the strongest negative effect on TTF regardless of ET duration (hazard ratio [HR] 1.84; 95%CI 1.49–2.27; p < 0.001). Conversely, capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in primary setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55–0.75; p < 0.001).

Conclusions

Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, Andre F, Harbeck N, Aguilar Lopez B, Barrios CH, Bergh J, Biganzoli L, Boers-Doets CB, Cardoso MJ, Carey LA, Cortes J, Curigliano G, Dieras V, El Saghir NS, Eniu A, Fallowfield L, Francis PA, Gelmon K, Johnston SRD, Kaufman B, Koppikar S, Krop IE, Mayer M, Nakigudde G, Offersen BV, Ohno S, Pagani O, Paluch-Shimon S, Penault-Llorca F, Prat A, Rugo HS, Sledge GW, Spence D, Thomssen C, Vorobiof DA, Xu B, Norton L, Winer EP (2018) 4th ESO-ESMO International consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol 29(8):1634–1657. https://doi.org/10.1093/annonc/mdy192CrossRefPubMed Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, Andre F, Harbeck N, Aguilar Lopez B, Barrios CH, Bergh J, Biganzoli L, Boers-Doets CB, Cardoso MJ, Carey LA, Cortes J, Curigliano G, Dieras V, El Saghir NS, Eniu A, Fallowfield L, Francis PA, Gelmon K, Johnston SRD, Kaufman B, Koppikar S, Krop IE, Mayer M, Nakigudde G, Offersen BV, Ohno S, Pagani O, Paluch-Shimon S, Penault-Llorca F, Prat A, Rugo HS, Sledge GW, Spence D, Thomssen C, Vorobiof DA, Xu B, Norton L, Winer EP (2018) 4th ESO-ESMO International consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol 29(8):1634–1657. https://​doi.​org/​10.​1093/​annonc/​mdy192CrossRefPubMed
3.
Zurück zum Zitat Rugo HS, Rumble RB, Macrae E, Barton DL, Connolly HK, Dickler MN, Fallowfield L, Fowble B, Ingle JN, Jahanzeb M, Johnston SR, Korde LA, Khatcheressian JL, Mehta RS, Muss HB, Burstein HJ (2016) Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 34(25):3069–3103. https://doi.org/10.1200/JCO.2016.67.1487CrossRefPubMed Rugo HS, Rumble RB, Macrae E, Barton DL, Connolly HK, Dickler MN, Fallowfield L, Fowble B, Ingle JN, Jahanzeb M, Johnston SR, Korde LA, Khatcheressian JL, Mehta RS, Muss HB, Burstein HJ (2016) Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 34(25):3069–3103. https://​doi.​org/​10.​1200/​JCO.​2016.​67.​1487CrossRefPubMed
4.
Zurück zum Zitat Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva-Vazquez R, Jung KH, Chakravartty A, Hughes G, Gounaris I, Rodriguez-Lorenc K, Taran T, Hurvitz S, Tripathy D (2019) Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med 381(4):307–316. https://doi.org/10.1056/NEJMoa1903765CrossRefPubMed Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva-Vazquez R, Jung KH, Chakravartty A, Hughes G, Gounaris I, Rodriguez-Lorenc K, Taran T, Hurvitz S, Tripathy D (2019) Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med 381(4):307–316. https://​doi.​org/​10.​1056/​NEJMoa1903765CrossRefPubMed
5.
Zurück zum Zitat Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke E-M, Conte P, Lu Y, Barriga S, Hurt K, Frenzel M, Johnston S, Llombart-Cussac A (2019) The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor–positive, erbb2-negative breast cancer that progressed on endocrine therapy MONARCH 2: a randomized clinical trial. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.4782CrossRefPubMedPubMedCentral Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke E-M, Conte P, Lu Y, Barriga S, Hurt K, Frenzel M, Johnston S, Llombart-Cussac A (2019) The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor–positive, erbb2-negative breast cancer that progressed on endocrine therapy MONARCH 2: a randomized clinical trial. JAMA Oncol. https://​doi.​org/​10.​1001/​jamaoncol.​2019.​4782CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat 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
7.
Zurück zum Zitat Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A (2017) MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35(25):2875–2884. https://doi.org/10.1200/JCO.2017.73.7585CrossRefPubMed Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A (2017) MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35(25):2875–2884. https://​doi.​org/​10.​1200/​JCO.​2017.​73.​7585CrossRefPubMed
11.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC, American Society of Clinical Oncology, Oncology College of American Pathologists (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134(7):e48–e72. https://doi.org/10.1043/1543-2165-134.7.e48CrossRef Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC, American Society of Clinical Oncology, Oncology College of American Pathologists (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134(7):e48–e72. https://​doi.​org/​10.​1043/​1543-2165-134.​7.​e48CrossRef
13.
Zurück zum Zitat Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Andre F, Puyana Theall K, Huang X, Giorgetti C, Huang Bartlett C, Cristofanilli M (2018) Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med 379(20):1926–1936. https://doi.org/10.1056/NEJMoa1810527CrossRefPubMed Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Andre F, Puyana Theall K, Huang X, Giorgetti C, Huang Bartlett C, Cristofanilli M (2018) Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med 379(20):1926–1936. https://​doi.​org/​10.​1056/​NEJMoa1810527CrossRefPubMed
14.
Zurück zum Zitat Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17(4):425–439. https://doi.org/10.1016/S1470-2045(15)00613-0CrossRefPubMed Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17(4):425–439. https://​doi.​org/​10.​1016/​S1470-2045(15)00613-0CrossRefPubMed
15.
Zurück zum Zitat Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS (2011) Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol 29(34):4498–4504. https://doi.org/10.1200/JCO.2010.33.9101CrossRefPubMed Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS (2011) Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol 29(34):4498–4504. https://​doi.​org/​10.​1200/​JCO.​2010.​33.​9101CrossRefPubMed
16.
Zurück zum Zitat Harbeck N, Saupe S, Jager E, Schmidt M, Kreienberg R, Muller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Luck HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE, Investigators P (2017) A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat 161(1):63–72. https://doi.org/10.1007/s10549-016-4033-3CrossRefPubMed Harbeck N, Saupe S, Jager E, Schmidt M, Kreienberg R, Muller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Luck HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE, Investigators P (2017) A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat 161(1):63–72. https://​doi.​org/​10.​1007/​s10549-016-4033-3CrossRefPubMed
17.
Zurück zum Zitat Talbot DC, Moiseyenko V, Van Belle S, O'Reilly SM, Alba Conejo E, Ackland S, Eisenberg P, Melnychuk D, Pienkowski T, Burger HU, Laws S, Osterwalder B (2002) Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines. Br J Cancer 86(9):1367–1372. https://doi.org/10.1038/sj.bjc.6600261CrossRefPubMedPubMedCentral Talbot DC, Moiseyenko V, Van Belle S, O'Reilly SM, Alba Conejo E, Ackland S, Eisenberg P, Melnychuk D, Pienkowski T, Burger HU, Laws S, Osterwalder B (2002) Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines. Br J Cancer 86(9):1367–1372. https://​doi.​org/​10.​1038/​sj.​bjc.​6600261CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Oshaughnessy JA, Blum J, Moiseyenko V, Jones SE, Miles D, Bell D, Rosso R, Mauriac L, Osterwalder B, Burger HU, Laws S (2001) Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12(9):1247–1254. https://doi.org/10.1023/a:1012281104865CrossRefPubMed Oshaughnessy JA, Blum J, Moiseyenko V, Jones SE, Miles D, Bell D, Rosso R, Mauriac L, Osterwalder B, Burger HU, Laws S (2001) Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12(9):1247–1254. https://​doi.​org/​10.​1023/​a:​1012281104865CrossRefPubMed
Metadaten
Titel
The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer
verfasst von
Sudpreeda Chainitikun
James P. Long
Ruben Rodriguez-Bautista
Toshiaki Iwase
Debu Tripathy
Takeo Fujii
Naoto T. Ueno
Publikationsdatum
27.07.2020
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05837-6

Weitere Artikel der Ausgabe 3/2020

Breast Cancer Research and Treatment 3/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.