Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: Primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET)

Guy Jerusalem, G. Mariani, E. M. Ciruelos, M. Martin, V. C G Tjan-Heijnen, P. Neven, J. G. Gavila, A. Michelotti, F. Montemurro, D. Generali, E. Simoncini, I. Láng, J. Mardiak, B. Naume, M. Camozzi, K. Lorizzo, S. Bianchetti, P. Conte

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. Patients and methods: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. Results: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. Conclusions: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. Clinical trial registration: EudraCT Number: 2012-000073-23.

Original languageEnglish
Article numbermdw249
Pages (from-to)1719-1725
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

exemestane
Compassionate Use Trials
Aromatase Inhibitors
Multicenter Studies
Hormones
Breast Neoplasms
Safety
Stomatitis
Confidence Intervals
Everolimus
Asthenia
Incidence

Keywords

  • Advanced breast cancer
  • BMI
  • Elderly
  • Everolimus
  • Hormone-receptor positive
  • Stomatitis

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors : Primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). / Jerusalem, Guy; Mariani, G.; Ciruelos, E. M.; Martin, M.; Tjan-Heijnen, V. C G; Neven, P.; Gavila, J. G.; Michelotti, A.; Montemurro, F.; Generali, D.; Simoncini, E.; Láng, I.; Mardiak, J.; Naume, B.; Camozzi, M.; Lorizzo, K.; Bianchetti, S.; Conte, P.

In: Annals of Oncology, Vol. 27, No. 9, mdw249, 01.09.2016, p. 1719-1725.

Research output: Contribution to journalArticle

Jerusalem, G, Mariani, G, Ciruelos, EM, Martin, M, Tjan-Heijnen, VCG, Neven, P, Gavila, JG, Michelotti, A, Montemurro, F, Generali, D, Simoncini, E, Láng, I, Mardiak, J, Naume, B, Camozzi, M, Lorizzo, K, Bianchetti, S & Conte, P 2016, 'Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: Primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET)', Annals of Oncology, vol. 27, no. 9, mdw249, pp. 1719-1725. https://doi.org/10.1093/annonc/mdw249
Jerusalem, Guy ; Mariani, G. ; Ciruelos, E. M. ; Martin, M. ; Tjan-Heijnen, V. C G ; Neven, P. ; Gavila, J. G. ; Michelotti, A. ; Montemurro, F. ; Generali, D. ; Simoncini, E. ; Láng, I. ; Mardiak, J. ; Naume, B. ; Camozzi, M. ; Lorizzo, K. ; Bianchetti, S. ; Conte, P. / Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors : Primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). In: Annals of Oncology. 2016 ; Vol. 27, No. 9. pp. 1719-1725.
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title = "Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: Primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET)",
abstract = "Background: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. Patients and methods: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. Results: The median treatment duration was 5.1 months [95{\%} confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95{\%} CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8{\%} of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2{\%} were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall {\%}, {\%} EVE-related) stomatitis (52.8{\%}; 50.8{\%}) and asthenia (22.8{\%}; 14.6{\%}). The most frequently reported hematologic AEs were (overall {\%}, {\%} EVE-related) anemia (14.4{\%}; 8.1{\%}) and thrombocytopenia (5.9{\%}; 4.6{\%}). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8{\%} versus 13.0{\%}). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5{\%} of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7{\%}), 66 (3.1{\%}) deaths were due to disease progression and 46 (2.2{\%}) due to AEs; 4 deaths were suspected to be EVE-related. Conclusions: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. Clinical trial registration: EudraCT Number: 2012-000073-23.",
keywords = "Advanced breast cancer, BMI, Elderly, Everolimus, Hormone-receptor positive, Stomatitis",
author = "Guy Jerusalem and G. Mariani and Ciruelos, {E. M.} and M. Martin and Tjan-Heijnen, {V. C G} and P. Neven and Gavila, {J. G.} and A. Michelotti and F. Montemurro and D. Generali and E. Simoncini and I. L{\'a}ng and J. Mardiak and B. Naume and M. Camozzi and K. Lorizzo and S. Bianchetti and P. Conte",
year = "2016",
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TY - JOUR

T1 - Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors

T2 - Primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET)

AU - Jerusalem, Guy

AU - Mariani, G.

AU - Ciruelos, E. M.

AU - Martin, M.

AU - Tjan-Heijnen, V. C G

AU - Neven, P.

AU - Gavila, J. G.

AU - Michelotti, A.

AU - Montemurro, F.

AU - Generali, D.

AU - Simoncini, E.

AU - Láng, I.

AU - Mardiak, J.

AU - Naume, B.

AU - Camozzi, M.

AU - Lorizzo, K.

AU - Bianchetti, S.

AU - Conte, P.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. Patients and methods: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. Results: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. Conclusions: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. Clinical trial registration: EudraCT Number: 2012-000073-23.

AB - Background: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. Patients and methods: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. Results: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. Conclusions: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. Clinical trial registration: EudraCT Number: 2012-000073-23.

KW - Advanced breast cancer

KW - BMI

KW - Elderly

KW - Everolimus

KW - Hormone-receptor positive

KW - Stomatitis

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U2 - 10.1093/annonc/mdw249

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