F. Lerebours (St. Cloud, France)

Hôpital René Huguenin - Institut Curie

Author Of 1 Presentation

 Conference Calendar
Proffered Paper session 1 Proffered paper

63O - Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: survival results of the UNICANCER-NeoPAL study (ID 239)

Presentation Number
63O
Lecture Time
14:16 - 14:26
Speakers
Session Name
Proffered Paper session 1
Room
Channel 2
Date
Fri, 07.05.2021
Time
14:15 - 15:30

Abstract

Background

The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups.

Methods

NeoPAL (UCBG104, NCT02400567) is a randomized, parallel, non-comparative phase II study. Postmenopausal women with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III BC, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks (LETPAL), or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) x3 21-day courses followed by docetaxel 100 mg/m2 x3 21-day courses (CT). Secondary endpoints included progression-free survival (PFS) and invasive-disease free survival (iDFS), all measured from the date of randomization. Exploratory objectives aimed at evaluating the impact of PEPI score and residual cancer burden (RCB) on survival outcomes in both arms.

Results

53 pts were randomized in each arm. 23 of the 53 pts in the LETPAL arm received postoperative adjuvant chemotherapy. Median follow-up is 40.4 months [0-56.6]. 11 progressions have been observed, of which 3 were in the LETPAL and 8 in the control arm. Two additional iDFS events were observed in the LETPAL arm (secondary malignancies). PFS (HR = 1.01; 95%CI [0.36; 2.90], p=0.98) and iDFS (HR= 0.83; 95%CI [0.31; 2.23], p=0.71) did not differ between both arms. 40 months PFS rate is 86.7% (78.0-96.4) and 87.2% (78.1-97.4) in LETPAL and CT arms respectively. PEPI (PEPI II/II vs I: HR 0.80, 95%CI 0.18-3.67) and RCB scores (RCB II/III vs 0/I: HR 1.36; 95%CI 0.17-10.6) did not appear as independent predictors of PFS or iDFS.

Conclusions

Despite its small size, NeoPAL suggests that a neoadjuvant LETPAL strategy, together with selected postoperative administration of chemotherapy, may spare chemotherapy in some pts with LBC while allowing good long-term outcomes.

Clinical trial identification

NCT02400567.

Legal entity responsible for the study

UNICANCER.

Funding

Pfizer, NanoString Technologies.

Disclosure

S. Delaloge: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Orion; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Pierre Fabre. H. Manduzio, J. Lemonnier, P.H. Cottu: Research grant/Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

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Author Of 3 Presentations

 On-Demand ePoster Display

104P - Clinical characteristics of patients (pts) with complete response (CR) to abemaciclib-based endocrine therapy (ET) in MONARCH 2 (M2) and MONARCH 3 (M3)

Abstract

Background

Abemaciclib is an oral cyclin-dependent kinase 4 & 6 inhibitor, dosed on a continuous schedule, approved for the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) combined with ET. In this pt population, CR is rarely seen with ET alone. Pt/disease characteristics may correlate with response to a specific treatment. In this post-hoc exploratory analysis, we report characteristics of pts with CR to abemaciclib+ET in M2 and M3.

Methods

M2 (NCT02107703) and M3 (NCT02246621) were double-blind, phase III studies in which women with HR+, HER2- ABC were randomised to receive abemaciclib/placebo+ET (M2: fulvestrant; M3: aromatase inhibitor). M2 included pts with progression during or ≤1 year of (neo)adjuvant ET or on first ET for ABC. M3 included pts who had not received prior systemic therapy for ABC. Disease characteristics were described in pts who achieved CR (RECIST v1.1) across the two studies, focusing on parameters reported to be associated with poor prognosis. Data are from the final progression-free survival analyses.

Results

Of 774 pts randomised to receive abemaciclib in M2 and M3, a total of 23 achieved CR: 14/446 in M2 and 9/328 in M3 (corresponding data in M2 and M3 pts receiving placebo+ET: 1/223 and 1/165 pts, respectively). A total of 3/14 M2 and 6/9 M3 abemaciclib pts had Eastern Cooperative Oncology Group (ECOG) status 1 (remainder: ECOG 0); 2/14 M2 and 0/9 M3 pts were progesterone receptor negative; 4/14 M2 and 3/9 M3 pts had a high-grade tumour; 10/14 M2 and 9/9 M3 pts had no bone-only disease, and 2/14 M2 and 0/9 M3 pts had liver metastases at baseline. Treatment-free interval was <3 years for 3/4 M3 pts with recurrent metastatic disease who had received adjuvant ET. 10/14 M2 pts and 5/9 M3 pts achieved CR <3 months after starting treatment; 7/14 M2 and 6/9 M3 pts had duration of response >15 months.

Conclusions

A small proportion of pts with recurrent ABC treated with abemaciclib in M2 and M3 achieved CR, including some pts with disease characteristics reported to be associated with poor prognosis. Those responses had a short time to onset and were relatively durable.

Editorial acknowledgement

Medical writing assistance was provided by Gill Gummer and Caroline Spencer (Rx Communications, Mold, UK).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Funded by Eli Lilly and Company.

Disclosure

J. Huober: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self): Hexal; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Daiichi; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie. N. Chouaki, C. Stoffregen, A. Korfel: Full/Part-time employment: Eli Lilly and Company. F. Lerebours: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Company; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

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113P - Efficacy of oral etoposide associated with trastuzumab in HER2-positive metastatic breast cancer: results from the Institut Curie’s database.

Abstract

Background

The TOP2A (encoding topoisomerase II) and HER2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. The topoisomerase-II inhibitor etoposide (oral VP16) has demonstrated clinical activity in metastatic breast cancer (MBC). However, the clinical benefit of trastuzumab combined with oral VP16 (T-VP16) in HER2+ MBC has not been evaluated.

Methods

Patients treated at Institut Curie Hospitals (Paris and Saint Cloud, France) with T-VP16 for HER2+ MBC were retrieved by an in-silico search. A waiver of informed consent was obtained from the local IRB. Clinical and pathological data were collected by trained medical oncologists. The primary study endpoint was progression-free survival (PFS) assessed by the Kaplan Meier method. Secondary endpoints were: overall survival (OS), long response rate (PFS>6 months), clinical benefit (defined as a PFS than 6 months AND longer than the PFS achieved by the previous line of treatment), response rate, and toxicity.

Results

From 2008 to 2016, 43 patients with HER2+ MBC who received T-VP16 were included. The median number of previous chemotherapy lines was 7 (range 1-13). The median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Twelve patients (27.9%) had a long response to treatment including nine (20.9%) with clinical benefit. A complete response was obtained for 3 patients. Only 4 patients stopped treatment for toxicity.

Conclusions

The favorable clinical benefit, good tolerance and low cost suggest that T-VP16 is a relevant option for patients with heavily pretreated HER2-positive MBC. TOP2A and HER2 co-amplification data will be presented at the meeting.

Legal entity responsible for the study

Institut Curie.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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151P - Impact of germline BRCA (gBRCA) mutation (m) status on clinical characteristics and patterns of care among women with early breast cancer (eBC): an analysis of the observational prospective CANTO cohort

Abstract

Background

Genetic mutations on breast cancer (BC) susceptibility genes such as BRCA 1 or 2, are well known risk factors for BC development. 5-10% of BC are associated with a gBRCAm, which can impact tumor characteristics and management of the associated BC. Using the French prospective ongoing CANTO cohort (NCT01993498) we conducted a retrospective analysis focusing on clinical characteristics and patterns of care of eBC by gBRCA status.

Methods

Data from 9368 women diagnosed with stage I to IIIa BC from 2012 to 2017 were analysed by BRCA status. Demographics, medical and family history, disease characteristics and BC treatment were examined overall and per subgroup populations.

Results

In this cohort, 169 (1.8%) patients (pts) had a gBRCAm (92 gBRCA1m and 77 gBRCA2m), 2226 (28%) were gBRCA wild type (wt) and 6573 (70.2%) gBRCA unknown (uk). Women with gBRCAm were younger than gBRCAwt or uk (mean age 43.7 years [95% CI: 42.0–45.4] versus (vs) 53.7 [53.2 - 54.1] vs 58.2 [57.9 - 58.5] respectively) at BC diagnosis. Tumours of pts with gBRCAm were characterized by higher proportion of triple negative (TN) subtype (44% [36.7-52.2] vs 13.3% [12.1 - 14.7] vs 7.9% [7.3 - 8.6]), higher stage II/IIIa (65.1% [57.4-72.2] vs 52.0% [50.0-53.9] vs 49.0% [47.8-50.2], higher histological grade 3 (67.9% [60.2-74.8] vs 32.9% [31.1-34.8] vs 25.5% [24.5-26.6]) when compared to gBRCAwt and uk pts. gBRCAm pts were more likely to undergo radical mastectomy (46.2% [35.0-50.4] vs 24.9% [23.3-26.6] vs 22.5% [21.5-23.6] ) with more axillary dissection (51.5% [43.7-59.2] vs 40.5% [38.4-42.2] vs 34.5% [33.4-35.7]) compared to gBRCAwt and uk pts. gBRCAm pts were also more likely to receive chemotherapy 92.9% [87.9-96.3] vs 56.4% [54.5-58.4] vs 49.4% [48.2-50.6] especially in the neo adjuvant setting (39.1% [31.6-46.8] vs 16.4% [15.0 -17.8] vs 11.5% [10.7-12.3]).

Conclusions

In our cohort, 30% of eBC pts had their gBRCAm status tested; of them 7.1% had gBRCAm 1 or 2. Consistent with prior research, women with gBRCAm had a substantial proportion of higher stage TN tumours and were treated with aggressive chemotherapy. Further studies on clinical outcomes of eBC pts with gBRCAm are warranted.

Clinical trial identification

NCT01993498.

Legal entity responsible for the study

UNICANCER.

Funding

This research was conducted with support from ANR (Agence Nationale de la Recherche) under the Call for Cohort Project - Investment of the Future reference ANR-10-COHO-04. The study was sponsored by AstraZeneca.

Disclosure

B. Pistilli: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Puma Biotechnology; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Myriad Genetics; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): MSD Oncology; Honoraria (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Merus. C.C. Jouannaud: Honoraria (self): Daiichi; Honoraria (self): Sankyo; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Travel/Accommodation/Expenses: Novartis. F. Lerebours: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. M. Campone: Honoraria (self), Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Speaker Bureau/Expert testimony: Accord; Honoraria (self): GT1; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Novartis. I. Vaz-Luis: Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Pfizer. All other authors have declared no conflicts of interest.

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