De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: Results of the PerELISA neoadjuvant study

V. Guarneri, M. V. Dieci, G. Bisagni, A. Frassoldati, G. V. Bianchi, G. L. De Salvo, E. Orvieto, L. Urso, T. Pascual, L. Paré, P. Galván, M. Ambroggi, C. A. Giorgi, G. Moretti, G. Griguolo, R. Vicini, A. Prat, P. F. Conte

Research output: Contribution to journalArticle

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Abstract

Background: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. Patients and methods: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. Results: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-Trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042). Conclusions: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-Term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT number: 2013-002662-40 ClinicalTrials.gov Identifier: NCT02411344.

Original languageEnglish
Article numbermdz055
Pages (from-to)921-926
Number of pages6
JournalAnnals of Oncology
Volume30
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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letrozole
Hormones
Breast Neoplasms
Therapeutics
Drug Therapy

Keywords

  • early breast cancer
  • HER2-positive breast cancer
  • neoadjuvant
  • pertuzumab
  • trastuzumab

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole : Results of the PerELISA neoadjuvant study. / Guarneri, V.; Dieci, M. V.; Bisagni, G.; Frassoldati, A.; Bianchi, G. V.; De Salvo, G. L.; Orvieto, E.; Urso, L.; Pascual, T.; Paré, L.; Galván, P.; Ambroggi, M.; Giorgi, C. A.; Moretti, G.; Griguolo, G.; Vicini, R.; Prat, A.; Conte, P. F.

In: Annals of Oncology, Vol. 30, No. 6, mdz055, 01.06.2019, p. 921-926.

Research output: Contribution to journalArticle

Guarneri, V. ; Dieci, M. V. ; Bisagni, G. ; Frassoldati, A. ; Bianchi, G. V. ; De Salvo, G. L. ; Orvieto, E. ; Urso, L. ; Pascual, T. ; Paré, L. ; Galván, P. ; Ambroggi, M. ; Giorgi, C. A. ; Moretti, G. ; Griguolo, G. ; Vicini, R. ; Prat, A. ; Conte, P. F. / De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole : Results of the PerELISA neoadjuvant study. In: Annals of Oncology. 2019 ; Vol. 30, No. 6. pp. 921-926.
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title = "De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: Results of the PerELISA neoadjuvant study",
abstract = "Background: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. Patients and methods: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20{\%} from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. Results: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-Trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5{\%}, 95{\%} confidence interval 11.1{\%} to 34.5{\%}). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3{\%} of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5{\%} versus 13.8{\%}, P = 0.042). Conclusions: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-Term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT number: 2013-002662-40 ClinicalTrials.gov Identifier: NCT02411344.",
keywords = "early breast cancer, HER2-positive breast cancer, neoadjuvant, pertuzumab, trastuzumab",
author = "V. Guarneri and Dieci, {M. V.} and G. Bisagni and A. Frassoldati and Bianchi, {G. V.} and {De Salvo}, {G. L.} and E. Orvieto and L. Urso and T. Pascual and L. Par{\'e} and P. Galv{\'a}n and M. Ambroggi and Giorgi, {C. A.} and G. Moretti and G. Griguolo and R. Vicini and A. Prat and Conte, {P. F.}",
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TY - JOUR

T1 - De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole

T2 - Results of the PerELISA neoadjuvant study

AU - Guarneri, V.

AU - Dieci, M. V.

AU - Bisagni, G.

AU - Frassoldati, A.

AU - Bianchi, G. V.

AU - De Salvo, G. L.

AU - Orvieto, E.

AU - Urso, L.

AU - Pascual, T.

AU - Paré, L.

AU - Galván, P.

AU - Ambroggi, M.

AU - Giorgi, C. A.

AU - Moretti, G.

AU - Griguolo, G.

AU - Vicini, R.

AU - Prat, A.

AU - Conte, P. F.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Background: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. Patients and methods: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. Results: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-Trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042). Conclusions: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-Term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT number: 2013-002662-40 ClinicalTrials.gov Identifier: NCT02411344.

AB - Background: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. Patients and methods: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. Results: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-Trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042). Conclusions: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-Term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT number: 2013-002662-40 ClinicalTrials.gov Identifier: NCT02411344.

KW - early breast cancer

KW - HER2-positive breast cancer

KW - neoadjuvant

KW - pertuzumab

KW - trastuzumab

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