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Poster Discussion - Breast cancer, early stage

4001 - Neoadjuvant endocrine therapy with palbociclib in patients with high-risk breast cancer

Date

28 Sep 2019

Session

Poster Discussion - Breast cancer, early stage

Presenters

Per Eystein Lønning

Citation

Annals of Oncology (2019) 30 (suppl_5): v55-v98. 10.1093/annonc/mdz240

Authors

P.E. Lønning1, C. Clausen2, E.S. Blix3, S. Lundgren4, G. Vagstad5, H. Espelid6, B. Gilje7, E.A. Janssen8, J. Geisler9, T. Aas10, H. Aase11, S. Knappskog2, H.P. Eikesdal1

Author affiliations

  • 1 Dept. Of Oncology, Haukeland University Hospital, 5021 - Bergen/NO
  • 2 Section Of Oncology, Dept. Of Clinical Science, University of Bergen, 5021 - Bergen/NO
  • 3 Dept. Of Oncology, University Hospital of North Norway, Tromsø/NO
  • 4 Dept. Of Oncology, St.Olavs University Hospital, Trondheim/NO
  • 5 Dept. Of Oncology, Førde Hospital, Førde/NO
  • 6 Dept. Of Surgery, Haugesund Hospital, Haugesund/NO
  • 7 Dept. Of Oncology, Stavanger University Hospital, Stavanger/NO
  • 8 Dept. Of Pathology, Stavanger University Hospital, Stavanger/NO
  • 9 Institute Of Clinical Medicine, University of Oslo, Akershus/NO
  • 10 Dept. Of Surgery, Haukeland University Hospital, 5021 - Bergen/NO
  • 11 Dept. Of Radiology, Haukeland University Hospital, 5021 - Bergen/NO

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Abstract 4001

Background

Optimal neoadjuvant therapy for luminal A breast cancer remains a topic of controversy.

Methods

In the phase 2 PETREMAC trial (NCT02624973), patients with large T2 (>4cm) or locally advanced breast cancers and luminal A characteristics (ER > 50%, HER2- and TP53 WT) received neoadjuvant endocrine therapy (NET) and CDK4/6 inhibition in concert. NET consisted of letrozole (postmenopausals) or tamoxifen + goserelin (premenopausals). Palbociclib (P) was added if Ki67 had decreased <50% after 14 days on NET. Neoadjuvant chemotherapy (NAC: docetaxel) was introduced if NET + P decreased Ki67 <50% or if NET +/- P did not cause an objective response (OR). Pre-treatment tumor biopsies underwent targeted DNA sequencing of 360 cancer-related genes.

Results

88 patients were enrolled; mean tumor diameter 55 mm (range 20-95). 2 patients lacked Ki67 data for analysis, 1 was a screening failure. 47/85 (55%) had a drop >50% on NET alone. Among the remaining 38 patients, 31 had P added in concert, 5 had Ki67<10% before NET and did not receive P, 2 had missing data. NET + P yielded a Ki67 drop >50% in 22/31 patients (71%). NAC was required in 28/84 patients (33%) after NET +/- P. Thus far, 84 patients have completed neoadjuvant treatment, and 75 have surgery results ready. The clinical OR rate (ORR) before surgery was 24/32 for NET alone, 12/15 for NET + P and 24/28 for NAC after NET +/- P. The overall ORR before surgery was 85% (60/75, 13 w/missing data), and ORR 77% (36/47) for NET +/- P. Pathological complete response (pCR) has been observed in 4/75 patients at surgery, where 3/4 with pCR received NAC after NET +/- P. 40/88 tumors (45%) had mutations in the PI3K pathway; PIK3CA (33%), PTEN (6.8%) and AKT1 (4.5%). 5/15 lobular carcinomas (33%) and 16/73 other carcinomas (22%) harbored CDH1 mutations. CDH1 mutations were associated with a higher probability of Ki67 reduction >50% on NET alone (CDH1 mutated: 15/20 vs CDH1 WT: 32/66; p = 0.042).

Conclusions

NET +/- P was effective at reducing cell proliferation and yielded an ORR of 77% in these ER+, HER2 negative breast cancers. NAC was required only among 33% of the patients. CDH1 mutations seem predictive of response to NET in this setting.

Clinical trial identification

NCT02624973; 2015-002816-34.

Editorial acknowledgement

Legal entity responsible for the study

Haukeland University Hospital, Bergen, Norway.

Funding

Det Regionale Samarbeidsorganet/Helse Vest, Pfizer.

Disclosure

P.E. Lønning: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Laboratorios Farmaceuticos Rovi; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Licensing / Royalties: Cytovation. E.S. Blix: Honoraria (self): Pfizer. B. Gilje: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Astellas Oncology; Research grant / Funding (institution): Cellgene; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Pierre Fabre. E.A. Janssen: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. J. Geisler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Speaker Bureau / Expert testimony: Brystol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer. T. Aas: Honoraria (self): AstraZenaca; Honoraria (self): Roche. S. Knappskog: Honoraria (self), Research grant / Funding (institution): AstraZenaca; Honoraria (self), Research grant / Funding (institution): Pfizer; Licensing / Royalties: Patent EP2389450 A1,Patent WO 2012/010661. H.P. Eikesdal: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZenaca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self): HAI Interaktiv AS; Honoraria (self): Dagens Medisin; Honoraria (self): Brystol-Myers-Squibb; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Abbvie. All other authors have declared no conflicts of interest.

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