Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer

Francesco Perrone, Michelino De Laurentiis, Sabino De Placido, Michele Orditura, Saverio Cinieri, Ferdinando Riccardi, Angela Stefania Ribecco, Carlo Putzu, Lucia Del Mastro, Emanuela Rossi, Vincenza Tinessa, Anna Maria Mosconi, Francesco Nuzzo, Francesca Di Rella, Adriano Gravina, Giovanni Iodice, Gabriella Landi, Carmen Pacilio, Valeria Forestieri, Rossella Lauria & 12 others Agnese Fabbri, Toni Ibrahim, Ermelinda De Maio, Sandro Barni, Stefania Gori, Vittorio Simeon, Laura Arenare, Gennaro Daniele, Maria Carmela Piccirillo, Nicola Normanno, Andrea de Matteis, Ciro Gallo

Research output: Contribution to journalArticle

Abstract

Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022)
Original languageEnglish
JournalEuropean Journal of Cancer
DOIs
Publication statusPublished - 2019

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zoledronic acid
letrozole
Breast Neoplasms
Triptorelin Pamoate
Disease-Free Survival
Confidence Intervals
Second Primary Neoplasms
Tamoxifen
Patient Safety
Survival Analysis
Compliance
Neoplasms
Breast
Hormones
Recurrence

Keywords

  • Adjuvant endocrine treatment
  • Aromatase inhibitors
  • Breast cancer
  • Phase 3
  • Premenopausal patients
  • Zoledronic acid

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Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer. / Perrone, Francesco; De Laurentiis, Michelino; De Placido, Sabino; Orditura, Michele; Cinieri, Saverio; Riccardi, Ferdinando; Ribecco, Angela Stefania; Putzu, Carlo; Del Mastro, Lucia; Rossi, Emanuela; Tinessa, Vincenza; Mosconi, Anna Maria; Nuzzo, Francesco; Di Rella, Francesca; Gravina, Adriano; Iodice, Giovanni; Landi, Gabriella; Pacilio, Carmen; Forestieri, Valeria; Lauria, Rossella; Fabbri, Agnese; Ibrahim, Toni; De Maio, Ermelinda; Barni, Sandro; Gori, Stefania; Simeon, Vittorio; Arenare, Laura; Daniele, Gennaro; Piccirillo, Maria Carmela; Normanno, Nicola; de Matteis, Andrea; Gallo, Ciro.

In: European Journal of Cancer, 2019.

Research output: Contribution to journalArticle

Perrone, F, De Laurentiis, M, De Placido, S, Orditura, M, Cinieri, S, Riccardi, F, Ribecco, AS, Putzu, C, Del Mastro, L, Rossi, E, Tinessa, V, Mosconi, AM, Nuzzo, F, Di Rella, F, Gravina, A, Iodice, G, Landi, G, Pacilio, C, Forestieri, V, Lauria, R, Fabbri, A, Ibrahim, T, De Maio, E, Barni, S, Gori, S, Simeon, V, Arenare, L, Daniele, G, Piccirillo, MC, Normanno, N, de Matteis, A & Gallo, C 2019, 'Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer', European Journal of Cancer. https://doi.org/10.1016/j.ejca.2019.05.004
Perrone, Francesco ; De Laurentiis, Michelino ; De Placido, Sabino ; Orditura, Michele ; Cinieri, Saverio ; Riccardi, Ferdinando ; Ribecco, Angela Stefania ; Putzu, Carlo ; Del Mastro, Lucia ; Rossi, Emanuela ; Tinessa, Vincenza ; Mosconi, Anna Maria ; Nuzzo, Francesco ; Di Rella, Francesca ; Gravina, Adriano ; Iodice, Giovanni ; Landi, Gabriella ; Pacilio, Carmen ; Forestieri, Valeria ; Lauria, Rossella ; Fabbri, Agnese ; Ibrahim, Toni ; De Maio, Ermelinda ; Barni, Sandro ; Gori, Stefania ; Simeon, Vittorio ; Arenare, Laura ; Daniele, Gennaro ; Piccirillo, Maria Carmela ; Normanno, Nicola ; de Matteis, Andrea ; Gallo, Ciro. / Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer. In: European Journal of Cancer. 2019.
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title = "Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer",
abstract = "Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4{\%}, 93.2{\%} and 93.3{\%} with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95{\%} confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95{\%} CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95{\%} CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3{\%}, 7.3{\%} and 16.6{\%} patients, and in the safety population, grade 3–4 side-effects were reported in 4.2{\%}, 6.9{\%} and 9.1{\%} patients treated with T, L or ZL, respectively. Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022)",
keywords = "Adjuvant endocrine treatment, Aromatase inhibitors, Breast cancer, Phase 3, Premenopausal patients, Zoledronic acid",
author = "Francesco Perrone and {De Laurentiis}, Michelino and {De Placido}, Sabino and Michele Orditura and Saverio Cinieri and Ferdinando Riccardi and Ribecco, {Angela Stefania} and Carlo Putzu and {Del Mastro}, Lucia and Emanuela Rossi and Vincenza Tinessa and Mosconi, {Anna Maria} and Francesco Nuzzo and {Di Rella}, Francesca and Adriano Gravina and Giovanni Iodice and Gabriella Landi and Carmen Pacilio and Valeria Forestieri and Rossella Lauria and Agnese Fabbri and Toni Ibrahim and {De Maio}, Ermelinda and Sandro Barni and Stefania Gori and Vittorio Simeon and Laura Arenare and Gennaro Daniele and Piccirillo, {Maria Carmela} and Nicola Normanno and {de Matteis}, Andrea and Ciro Gallo",
year = "2019",
doi = "10.1016/j.ejca.2019.05.004",
language = "English",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer

AU - Perrone, Francesco

AU - De Laurentiis, Michelino

AU - De Placido, Sabino

AU - Orditura, Michele

AU - Cinieri, Saverio

AU - Riccardi, Ferdinando

AU - Ribecco, Angela Stefania

AU - Putzu, Carlo

AU - Del Mastro, Lucia

AU - Rossi, Emanuela

AU - Tinessa, Vincenza

AU - Mosconi, Anna Maria

AU - Nuzzo, Francesco

AU - Di Rella, Francesca

AU - Gravina, Adriano

AU - Iodice, Giovanni

AU - Landi, Gabriella

AU - Pacilio, Carmen

AU - Forestieri, Valeria

AU - Lauria, Rossella

AU - Fabbri, Agnese

AU - Ibrahim, Toni

AU - De Maio, Ermelinda

AU - Barni, Sandro

AU - Gori, Stefania

AU - Simeon, Vittorio

AU - Arenare, Laura

AU - Daniele, Gennaro

AU - Piccirillo, Maria Carmela

AU - Normanno, Nicola

AU - de Matteis, Andrea

AU - Gallo, Ciro

PY - 2019

Y1 - 2019

N2 - Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022)

AB - Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022)

KW - Adjuvant endocrine treatment

KW - Aromatase inhibitors

KW - Breast cancer

KW - Phase 3

KW - Premenopausal patients

KW - Zoledronic acid

U2 - 10.1016/j.ejca.2019.05.004

DO - 10.1016/j.ejca.2019.05.004

M3 - Article

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -