Mini Oral session
Date
18.09.2020
Chairs
  • Francois-Clement Bidard (Paris, France)
  • Judith Bliss (London, United Kingdom)
  • Laura Biganzoli (Prato, Italy)
Mini Oral - Breast cancer, metastatic Mini Oral session

Open & welcome

Speakers
  • Laura Biganzoli (Prato, Italy)
Mini Oral - Breast cancer, metastatic Mini Oral session

277MO - SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), in ER+/ HER2- metastatic breast cancer (mBC): Biomarker analyses from a phase I/II study

Presentation Number
277MO
Speakers
  • Sarat Chandarlapaty (New York, NY, United States of America)

Abstract

Background

SAR439859 has antitumor activity in patients (pts) with wild type (WT) and mutated ESR1 mBC. Here we describe tumor molecular features and evidence of on target activity in SAR439859-treated pts.

Methods

Plasma circulating cell-free DNA (cfDNA) and paired biopsies were collected at baseline (BL), on treatment (OT) and end of treatment (EOT: cfDNA only) from heavily pretreated postmenopausal pts with ER+/HER2- mBC who received SAR439859 monotherapy (Part A: dose range 20–600 mg QD; Part B: 400 mg QD) in a phase I/II study (NCT03284957). In cfDNA at BL and EOT, mutation (mut) analysis was performed on a next generation sequencing panel of 77 genes. ESR1 muts in cfDNA at BL and OT were assessed by droplet digital polymerase chain reaction (ddPCR). In tumor tissue, ER and progesterone receptor (PgR), Ki67 and Bcl-2 expression over time were assessed by immunohistochemistry; changes in ER signaling pathway activation were assessed by gene set variation analysis (RNA sequencing). Response was assessed in pts who received SAR439859 ≥150 mg QD.

Results

At BL, in cfDNA from 63 pts, 95% had ≥1 mut, 52% had ≥1 ESR1 mut, 92% had ≥1 non-ESR1 mut and 49% had concurrent ESR1 and other muts. Most prevalent BL non-ESR1 muts were in PIK3CA (44% of pts), EGFR (33%), TP53 (30%) and MET (25%). ESR1 muts most commonly detected at BL and EOT were D538G, Y537S and Y537N. ESR1 muts tended to decrease OT; of 14 pts with ESR1 muts at BL, 2 had WT ESR1 OT. In 8 paired biopsies (7 were highly proliferative luminal B tumors), ER, PgR and Ki67 decreased (median relative change from BL: -58%, -88% and -33%), while Bcl-2 increased (24%). ER activation score decreased in 3/5 paired biopsies tested (median change from BL -0.38). SAR439859 showed clinical benefit (complete response + partial response [PR] + stable disease ≥24 weeks) in 40% (12/30) of WT ESR1 pts and 32% (9/28) of mutated ESR1 pts, per ddPCR. Of the 5 pts with PRs, 4 had WT ESR1 and 1 had 2 ESR1 muts, at BL.

Conclusions

Common genomic alterations, including in ESR1 and PIK3CA, were detected in most mBC pts. SAR439859 showed clinical benefit irrespective of ESR1 mut status and resulted in ER degradation and pathway inhibition in heavily pretreated pts.

Clinical trial identification

NCT03284957.

Editorial acknowledgement

Editorial support was provided by Jade Drummond and Michelle Daniels of inScience Communications, funded by Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

S. Chandarlapaty: Honoraria (self): Paige.ai; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Daiichi Sankyo. A. Bardia: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Daiichi/AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: PUMA; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Radius Health; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Immunomedics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Phillips; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Licensing/Royalties: Up-To-Date. S. Lord: Honoraria (self): Eisai; Honoraria (self): Prosigna; Advisory/Consultancy: Shionogi; Research grant/Funding (self): CRUK; Research grant/Funding (self): Against Breast Cancer; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Synthon; Travel/Accommodation/Expenses: Piqur Therapeutics; Shareholder/Stockholder/Stock options: Mitox. V. Pelekanou: Full/Part-time employment: Sanofi. N. Ternes: Full/Part-time employment: Sanofi R&D . J. Ming: Shareholder/Stockholder/Stock options, Full/Part-time employment: Sanofi. V. Boutet: Full/Part-time employment: Sanofi. E. Boitier: Full/Part-time employment: Sanofi. A. Gosselin: Full/Part-time employment: Sanofi. J. Sang Lee: Full/Part-time employment: Sanofi. W. Dos-Santos Bele: Full/Part-time employment: Sanofi. A. Protopopov: Full/Part-time employment: Sanofi. M. Celanovic: Full/Part-time employment: Sanofi. A-L. Bauchet: Honoraria (self), Full/Part-time employment: Sanofi. M. Campone: Honoraria (self), Advisory/Consultancy: GT1; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy: Pierre Fabre; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Servier; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (institution), Advisory/Consultancy: Accord; Honoraria (institution), Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Novartis-Lilly. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

278MO - cfDNA analysis from phase I/II study of lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2- advanced breast cancer patients

Presentation Number
278MO
Speakers
  • Boris Krastev (Sofia, Bulgaria)

Abstract

Background

Despite significant improvements in progression-free survival for patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with approved CDK4/6 inhibitors combined with fulvestrant, treatment is limited by neutropenia and gastrointestinal (GI) side effects. Lerociclib, dosed twice daily (BID) with no drug holiday in combination with fulvestrant, has a favorable safety profile with low rates of GI adverse events and Grade 3/4 neutropenia, as well as encouraging antitumor activity in pts with HR+/HER2- ABC (NCT02983071). Cell-free DNA (cfDNA) analysis in peripheral blood was conducted to characterize mechanisms of response and resistance in pts that received lerociclib and fulvestrant.

Methods

Pts with pretreated ABC were enrolled across doses of lerociclib 200–650 mg once daily and 100–250 mg BID in combination with fulvestrant 500 mg. Peripheral blood samples were drawn and cfDNA was isolated at baseline, cycle 1 day 15, each time point when tumor assessments were performed during the treatment period, and at the end of treatment. Samples were analyzed using the Guardant360 platform.

Results

Currently, 58 pts have been evaluated at baseline, with 44 pts (75.9%) harboring at least one somatic single nucleotide variant (mutation) in the genes evaluated. Seventeen pts (29.3%) harbored mutations in PIK3CA, with H1047R being the most common (8/17, 47.1%). Seven pts (12.1%) harbored mutations in ESR1, with D583G being the most common (4/7, 57.1%). No pts had mutations in both ESR1 and PIK3CA at baseline. Additionally, 3 pts (5.2%), 2 pts (3.4%), and 1 pt (1.7%) had mutations in genes at baseline associated with CDK4/6 resistance (RB1, CCND1, and CCNE1, respectively). Additional analyses of cfDNA (cycle 1 day 15 and end of treatment) along with correlation of cfDNA dynamics with clinical response are ongoing and will be presented.

Conclusions

The most common baseline mutations detected were PIK3CA and ESR1. Additional analyses, including cycle 1 day 15 change from baseline and correlation with clinical response, are anticipated to help elucidate predictors of response and/or resistance to the combination of lerociclib and fulvestrant in patients with HR+ ABC.

Clinical trial identification

NCT02983071.

Legal entity responsible for the study

G1 Therapeutics, Inc.

Funding

G1 Therapeutics, Inc.

Disclosure

B. Krastev: Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Luitpold Pharmaceuticals; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): Merck; Honoraria (self): Bayer; Honoraria (self): Eli Lilly; Honoraria (self): Amgen; Honoraria (self): Astellas; Honoraria (self): Mundipharma; Honoraria (self): Angelini. R. Rai: Full/Part-time employment: G1 Therapeutics. H-T. Arkenau: Honoraria (self), Research grant/Funding (institution): Guardant Health; Honoraria (self): Roche. R.D. Baird: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Molecular Partners; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Shionogi; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Carrick Therapeutics. A.M. Wardley: Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (self): Roche; Research grant/Funding (self): Novartis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (self): Eli Lilly; Travel/Accommodation/Expenses: MSD; Research grant/Funding (self): Athenex; Research grant/Funding (self): AstraZeneca; Honoraria (self): Andrew Wardley Limited; Officer/Board of Directors: Manchester Cancer Academy; Officer/Board of Directors: Outreach Research & Innovation Group Limited; Honoraria (self): Gerson Lehman Group; Honoraria (self): Guidepoint Global; Honoraria (self): Coleman Expert Network; Honoraria (self): Helios; Honoraria (self): Health Care America. R. Roylance: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: G1Therapeutics; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: AstraZeneca. W. Tao: Full/Part-time employment: G1 Therapeutics. A.P. Beelen: Full/Part-time employment: G1 Therapeutics. J.A. Sorrentino: Full/Part-time employment: G1 Therapeutics. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

Invited Discussant 277MO and 278MO

Speakers
  • Francois-Clement Bidard (Paris, France)
Mini Oral - Breast cancer, metastatic Mini Oral session

279MO - Divergent evolution of overall survival across metastatic breast cancer (MBC) subtypes in the nationwide ESME real life cohort 2008-2016

Presentation Number
279MO
Speakers
  • Suzette Delaloge (Villejuif, France)

Abstract

Background

Treatment (trt) strategies for HER2+ and HER2-/hormone receptor-positive (HR+) MBC have made great strides over the past 10 years (yrs). Real world data evaluate the final impact of care strategies.

Methods

ESME gathers full clinical data of all pts who initiated MBC trt in 18 French Cancer Centers between 01/2008-12/2016 (N=22109). Primary objective: prognostic effect of yr of diagnosis (YOD) on overall survival (OS) among pts with the 3 main subtypes: HR+/HER2- (n = 13656), HER2+ (n = 4017), triple-negative (TNBC) (n = 2963). We used multivariate adjusted Cox regression analyses including classical prognostic factors (R software).

Results

Median follow-up was 51.8 months (mo) (95%CI 51-52.7). YOD had no effect on the OS of TNBC pts. However, YOD >2013 appeared as an independent predictor of better OS in pts with HER2+ MBC, while it had an opposite effect in HR+/HER2- cases (Table). In the latter, median OS was 36.7 mo (95% CI: 35-38.7) YOD 2015 versus 44.5 mo (42.1-47.7) YOD 2008. Several sensitivity analyses showed similar trends. We will present explanatory analyses. Unlike baseline characteristics and adjuvant trts, MBC trts progressively changed during this pre-CDK period (including less CT).

HER2+ HR+/HER2-
HR (95% CI) p HR (95% CI) p
YOD (Ref 2008)
2009-2011 NS NS NS NS
2012 0.84 (0.71-0.99) .04 0.99 (0.91-1.09) .90
2013 0.75 (0.63-0.90) .002 1.02 (0.93-1.12) .67
2014 0.72 (0.59-0.88) .001 1.17 (1.06-1.30) .002
2015 0.69 (0.55-0.86) .001 1.17 (1.05-1.31) .005
2016 0.59 (0.45-0.78) <.001 1.20 (1.06-1.37) .005
Age at MBC (per yr) 1.02 (1.01-1.02) <.001 1.01 (1.01-1.02) <.001
Cancer-free interval 6-24 mo (Ref <6) 2.67 (2.34-3.04) <.001 2.50 (2.30-2.72) <.001
>24 mo 1.34 (1.21-1.48) <.001 1.15 (1.09-1.21) <.001
Visceral disease 1.48 (1.33-1.65) <.001 1.56 (1.47-1.63) <.001
Number of MBC sites ≥ 3 1.85 (1.66-2.06) <.001 1.39 (1.31-1.47) <.001

Conclusions

OS of pts with HER2+ MBC has dramatically improved over the past decade. However, it unexpectedly worsened among those with luminal cancers. These data prompt careful surveillance of real life outcomes as indicators of the final impact of global trt strategies.

Clinical trial identification

NCT0327531.

Legal entity responsible for the study

Unicancer.

Funding

Pfizer, Roche, AstraZeneca, Daiichi, Pierre Fabre, Novartis.

Disclosure

S. Delaloge: Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Puma; Honoraria (institution), Research grant/Funding (institution): Sanofi; Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution), Research grant/Funding (institution): Pierre Fabre; Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Daiichi. W. Jacot: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Honoraria (self): MSD; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Travel/Accommodation/Expenses: Roche. P.H. Cottu: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self): Lilly; Research grant/Funding (institution): Novartis. F. Dalenc: Travel/Accommodation/Expenses: Roche; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Roche. A. Gonçalves: Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution): Lilly; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pfizer. A. Patsouris: Honoraria (institution): Lilly; Honoraria (institution), Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. A. Mailliez: Honoraria (institution): Pfizer; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pierre Fabre. F. Clatot: Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Merck; Research grant/Funding (self): AstraZeneca. C. Levy: Honoraria (self): Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): MSD; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Daiichi. M. Robain: Research grant/Funding (institution): Roche; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): MSD; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): GSK. T. Bachelot: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Seattle genetics. E. Brain: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): BMS; Honoraria (self): Celgene; Honoraria (self): Clinigen; Honoraria (self): G1 therapeutics; Honoraria (self): Hospira; Honoraria (self): Jansen; Honoraria (self): Mylan; Honoraria (self): OBI pharma; Honoraria (self): Pfizer; Honoraria (self): Puma; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Samsung; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: Sandoz. D. Perol: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): BMS; Honoraria (self): Lilly; Honoraria (self): Ipsen; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): MSD; Honoraria (self): Takeda. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

280MO - Progression free survival with endocrine therapy, before or after chemotherapy, in patients with hormone receptor-positive/HER2-negative metastatic breast cancer in a large multicenter national observational study

Presentation Number
280MO
Speakers
  • Pauline Corbaux (Pierre BĂ©nite, France)

Abstract

Background

For HR+/HER2– metastatic breast cancer (mBC), the use of frontline endocrine therapy (ET) before chemotherapy (CT) is recommended by international guidelines, except in case of visceral crisis, for which CT is advised. However, before routine use of Cyclin-Dependent Kinase 4/6 inhibitors, many patients (pts) were given CT as first therapeutic line (L1). We aimed to compare the progression free survival (PFS) under ET, depending on whether it was given before or after any CT.

Methods

All pts who initiated treatment for a newly diagnosed mBC between 2008 and 2014 in all 18 French Comprehensive Cancer Centers were included in the ESME (Epidemiological Strategy and Medical Economics) mBC database. ESME collects and centralizes retrospective real-world data. Primary endpoint of the present study was the evaluation of PFS under the first ET (PFS-ET1), depending on its position in relation to CT. PFS-ET1 was defined as time between the starting date of first ET and first disease progression or death. Secondary endpoint was PFS under the second ET (PFS-ET2).

Results

Out of 16702 pts in ESME mBC database, 6293 pts with HR+/HER2- mBC who received at least one ET as metastatic disease were included. Median age at mBC diagnosis was 62.0 years (95%CI 23-96). Median follow-up reached 44.7 months (mo). As L1, 3832 (60.9%) pts received ET without CT (ET first group (ET1G)), while 2461 (39.1%) received CT (CT first group (CT1G)), with 2024 (32.2%) receiving ET as maintenance treatment (ET-M) after CT. Pts in CT1G were younger (median age 57.0 vs. 66.0, p<0.001) and more likely to have visceral metastases (59.5% vs. 39.4%, p<0.001). Median PFS-ET1 was 12.4 mo in ET1G vs. 12.6 mo in CT1G (HR 0.96, [95% CI 0.90;1.01], log-rank p=0.13). 1668 pts received at least two ET: 1069 (64.1%) as second-line therapy (L2) after L1 ET (ET1G) and 599 (36.0%) (CT1G) after at least one CT, with 279 (16.7%) as ET-M after CT L2. Median PFS-ET2 was 5.8 mo for ET1G vs. 5.6 mo for CT1G (HR 1.07 [95% CI 0.96;1.19], log-rank p=0.20).

Conclusions

In this large series of HR+/HER2– mBC pts, there was no difference in PFS on ET if it was given before or after CT. This was true both for first- and second-line ET.

Legal entity responsible for the study

R&D UNICANCER.

Funding

Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo.

Disclosure

A. Mailliez: Honoraria (self): Pfizer; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pierre Fabre. F. Le Du: Advisory/Consultancy: Lilly; Advisory/Consultancy: SeaGen; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Eisai. J-S. Frenel: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: GSK; Advisory/Consultancy: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. T. Bachelot: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Seattle Genetics. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

281MO - Clinicopathological characteristics and prognosis of breast cancer patients with isolated central nervous system metastases in the multicentre ESME database

Presentation Number
281MO
Speakers
  • Marcela Carausu (Saint-Cloud, France)

Abstract

Background

As a result of therapeutic and diagnostic advances, there is an increase of metastatic breast cancer (MBC) with first isolated central nervous system (CNS) metastases, for which there is no standard of care. The present study describes the largest-to-date real-life cohort of MBC patients with this clinical picture.

Methods

We retrospectively analyzed data from the ESME MBC French database including pts who initiated care for MBC between 2008-2016. The primary objective was to report the characteristics, management, and outcomes of those with first isolated CNS metastases, excluding pts with intrathecal treatment (IT) for leptomeningeal disease. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Descriptive statistics and multivariate Cox model were used.

Results

Of the 22,266 pts in the database, 541 (2.4%) had first isolated CNS metastases and no IT: median age was 57 years, median time to MBC, 22.8 months (mo). HER2+ cases were more frequent than the triple-negative (TN) or HR+/HER2- ones (41.6% vs. 26.1% vs. 28.5%, p<0.01). Treatment consisted of both local and systemic therapy (49.5%), only local (17.9%), only systemic (11.5%), or no treatment (18.5%). After a median follow-up of 43.3 mo, median first-line PFS and OS were 6.1 mo (95%CI: 5.7-6.8) and 20.7 mo (95%CI: 17.3-24.3). Older age, TN subtype, MBC-free interval (6-12 mo), lower PS and whole-brain radiotherapy were associated with worse survival by multivariate analysis. Median OS in the HR+/HER2+, HR+/HER2-, HR-/HER2+ and TN subgroups were 37.9 mo (95%CI: 25.9-47.6), 22.9 mo (95% CI: 17.1-31.9), 19.2 mo (95% CI: 14.3-28.9) and 11.5 mo (95%CI: 9.6-15.4), respectively. Compared with none, the use of systemic therapy within 3 months was associated with a better median OS by univariate analysis (24.1 vs. 16.1 mo (HR=0.8 [95%CI: 0.6-1.0], p=0.031), not confirmed by multivariate analysis (HR=1.0 [95%CI: 0.7-1.3], p=0.806).

Conclusions

MBC patients with first isolated CNS metastases, excluding leptomeningeal disease, represent a distinct population with specific management. In this context, the role of systemic therapy needs to be further investigated in prospective studies.

Clinical trial identification

NCT03275311.

Legal entity responsible for the study

UNICANCER.

Funding

UNICANCER. The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analysis and publication are managed entirely by R&D UNICANCER independently of the industrial consortium.

Disclosure

A. Patsouris: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (institution): Lilly. C. Levy: Honoraria (self): Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): MSD; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Daiichi. A. Gonçalves: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution): Lilly. T. Bachelot: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Seattle Genetics. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

Invited Discussant 279MO, 280MO and 281MO

Speakers
  • Judith Bliss (London, United Kingdom)
Mini Oral - Breast cancer, metastatic Mini Oral session

282MO - Abraxane plus cisplatin compared with gemcitabine plus cisplatin as first-line treatment in patients with metastatic triple-negative breast cancer (GAP): A multicenter, randomized, open-label, phase III trial

Presentation Number
282MO
Speakers
  • Xichun Hu (Shanghai, China)

Abstract

Background

Cisplatin showed great clinical benefit in metastatic triple-negative breast cancer (mTNBC) and has been included as first-line treatment when combined with gemcitabine in Chinese as well as German AGO guidelines. However, an optimal partner with cisplatin remains to be exploited. As nanoparticle albumin-bound (nab)-paclitaxel gained a high response in the treatment of mTNBC, we conducted GAP trial to assess the efficacy and safety of nab-paclitaxel plus cisplatin (AP) versus GP as first-line therapy for patients with mTNBC.

Methods

In this phase III trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive AP (nab-paclitaxel 125mg/m2 on day 1, 8 and cisplatin 75 mg/m2 on day 1) or GP (gemcitabine 1250 mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1) intravenously every 3 weeks until progression disease, intolerable toxicity or withdrawal of consent. The primary endpoint was progression-free survival (PFS) and secondary end points included overall response rate (ORR), overall survival (OS) and safety.

Results

127 patients received AP and 126 received GP from 9 centers (median follow-up, 17.8 months for AP group and 14.9 months for GP group). The median PFS was 9.9 months with AP, as compared with 7.5 months with GP (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.50-0.87; P=0.004). The ORR was significantly higher with AP (81.1%, vs. 56.3% with GP; P<0.001). A trend for improved OS in the AP group was observed (median, not reached; HR, 0.75; 95% CI, 0.51-1.11; P=0.16). Of the grade 3 or 4 adverse events, there was a significantly higher incidence of neuropathy (18.8% vs. 0%) in the AP group, and thrombocytopenia (3.9% vs. 29.4 %) in the GP group. Serious adverse events occurred in 3.9% patients (5/127) in the AP group and 2.4% patients (3/126) of patients in the GP group.

Conclusions

Nab-paclitaxel plus cisplatin improved PFS and ORR in patients with metastatic triple-negative breast cancer as a first-line treatment, as compared with GP, while OS results are much awaited. Safety profiles of the two combinations were different but the adverse events were manageable.

Clinical trial identification

NCT02546934.

Legal entity responsible for the study

The authors.

Funding

Fudan University Shanghai Cancer Center.

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

283MO - Ipatasertib (IPAT) + paclitaxel (PAC) for PIK3CA/AKT1/PTEN-altered hormone receptor-positive (HR+) HER2-negative advanced breast cancer (aBC): Primary results from Cohort B of the IPATunity130 randomised phase III trial

Presentation Number
283MO
Speakers
  • Nicholas Turner (London, United Kingdom)

Abstract

Background

PI3K/AKT pathway alterations occur in ∼50% of HR+ breast cancers. In a phase II trial in triple-negative aBC, adding IPAT to PAC improved progression-free survival (PFS), especially in patients (pts) with PIK3CA/AKT1/PTEN-altered tumours [Kim 2017].

Methods

IPATunity130 Cohort B enrolled pts with HR+ HER2– PIK3CA/AKT1/PTEN-altered measurable aBC suitable for chemotherapy (CT). Pts with prior CT for aBC or relapse <1 y since (neo)adjuvant CT were ineligible. Pts were randomised 2:1 to IPAT (400 mg d1–21) + PAC (80 mg/m2 d1, 8 & 15) on a 28 d cycle or placebo (PBO) + PAC until progression or unacceptable toxicity, stratified by (neo)adjuvant CT, prior PI3K/mTOR inhibitor and region. The primary endpoint was investigator-assessed PFS.

Results

146 pts were randomised to IPAT + PAC and 76 to PBO + PAC. Prior therapy was balanced between arms, with (neo)adjuvant CT in 55%, endocrine therapy for aBC in 46%, PI3K/mTOR inhibitor in 24% and CDK4/6 inhibitor in 26%. At data cut-off (17/1/20; median follow-up 12.9 mo) 21% of pts remained on therapy. Median investigator-assessed PFS was 9.3 mo in both arms (HR 1.00, 95% CI 0.71–1.40). Median PFS by independent review committee was 9.2 mo with IPAT + PAC vs. 8.5 mo with PBO + PAC (HR 0.79, 95% CI 0.56–1.13). In both arms, objective response rate was 47% and median response duration was 9.2 mo. Overall survival (OS) results are immature (deaths in 25%). Median PAC duration was 6.9 mo with IPAT + PAC vs. 8.8 mo with PBO + PAC; median duration of IPAT was 8.0 mo and PBO was 9.1 mo. IPAT + PAC was associated with more AEs leading to withdrawal of PAC (26% vs. 13%) or IPAT/PBO (11% vs. 4%). IPAT/PBO dose reductions were more common (34% vs. 8%) but PAC dose reductions (26% vs. 24%) and interruptions (53% vs. 51%) and IPAT/PBO interruptions (43% vs. 43%) were similar. No new safety signals were seen. The most common AEs were diarrhoea (85% vs. 37%; grade ≥3: 12% vs. 1%), alopecia (50% vs. 59%) and nausea (41% vs. 20%).

Conclusions

Adding IPAT to PAC did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ aBC. The IPAT + PAC safety profile was consistent with known AEs of each agent. OS follow-up is ongoing.

Clinical trial identification

NCT03337724.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

N. Turner: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharpe and Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Advisory/Consultancy: Bicycle Therapeutics; Honoraria (self), Advisory/Consultancy: Taiho; Honoraria (self), Advisory/Consultancy: Zeno Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Repare Therapeutics; Research grant/Funding (institution): BioRad; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Guardant Health. R. Dent: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Eisai; Honoraria (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca. J. O'Shaughnessy: Honoraria (self), Advisory/Consultancy: AbbVie Inc; Honoraria (self), Advisory/Consultancy: Agendia; Honoraria (self), Advisory/Consultancy: Amgen Biotechnology; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Celgene Corporation; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GRAIL; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Heron Therapeautics; Honoraria (self), Advisory/Consultancy: Ipsen Biopharmaceuticals; Honoraria (self), Advisory/Consultancy: Jounce Therapeutics; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Myriad; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ondonate Therapeutics; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Prime Oncology; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Syndax Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Takeda. S-B. Kim: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: Enzychem; Advisory/Consultancy: Dae Hwa Pharmaceutical Co. Ltd; Advisory/Consultancy: ISU Abxis; Advisory/Consultancy: Daiichi-Sankyo; Research grant/Funding (institution): Sanofi-Aventis; Research grant/Funding (institution): Kyowa-Kirin Inc; Research grant/Funding (institution): DongKook Pharm Co. S. Isakoff: Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy: Hengrui; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Mylan; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Oncopep Research ; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): PharmaMar. S. Saji: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Kyowa-Kirin; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self): Pfizer; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Taiho Pharmaceutical. Z. Nowecki: Travel/Accommodation/Expenses: Roche. Q. Lian: Shareholder/Stockholder/Stock options: Roche; Shareholder/Stockholder/Stock options: AbbVie; Shareholder/Stockholder/Stock options: Gilead; Full/Part-time employment: GNE/Roche. S-J. Reilly: Full/Part-time employment: Roche. H. Hinton: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Wongchenko: Full/Part-time employment: GNE/Roche; Shareholder/Stockholder/Stock options: Roche. A. Mani: Full/Part-time employment: GNE/Roche; Shareholder/Stockholder/Stock options: Roche. M. Oliveira: Advisory/Consultancy, Research grant/Funding (institution): GNE; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): PUMA Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Philips; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Zenith Epigenetics; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Piqur; Non-remunerated activity/ies, Member of Executive Board: SOLTI Breast Cancer Research Group. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

LBA20 - Vandetanib plus fulvestrant versus placebo plus fulvestrant after relapse or progression on an aromatase inhibitor in metastatic ER positive breast cancer (FURVA): A randomised, double-blind, placebo-controlled, phase II trial

Presentation Number
LBA20
Speakers
  • Robert Jones (Cardiff, United Kingdom)

Abstract

Background

Vandetanib is a multi-kinase inhibitor of VEGFR, EGFR and RET. Preclinical data suggests an activated RET pathway can contribute to endocrine resistance. The FURVA trial investigated whether the addition of vandetanib (v) to fulvestrant (f) improved progression-free survival in patients with aromatase inhibitor (AI) resistant advanced breast cancer.

Methods

FURVA is an investigator-led, double-blind, placebo-controlled, randomised phase II trial. AI resistant patients were recruited from 19 UK sites and randomly assigned (1:1) to fulvestrant 500mg (day 1 and 15 of cycle 1 and day 1 only of subsequent 28 day cycles) with either vandetanib 300mg (f+v) or placebo (f+p) daily until disease progression, unacceptable toxicity or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), safety, and the influence of RET signalling pathway component expression (e.g. total RET immunostaining) on vandetanib activity.

Results

Between 20 Apr 2015 and 30 Oct 2017, 165 patients were randomised to f+v (n=80) or f+ p (n=85). In the Intention-to-treat analysis, after 138 events, median PFS was 5.5 months (m) for f+v compared to 5.5m for f+p (Hazard Ratio (HR) 0.88; 95% CI: 0.62 to 1.23; p = 0.22). Median OS was 19.5m for f+v compared to 19.9m for f+p (HR=0.92; 95% CI: 0.60 to 1.42; p = 0.71). Unexpectedly, high total RET protein expression was associated with a significant PFS advantage of 8.87m vs 3.94m in the low RET group (HR 0.493: 95% CI 0.32 to 0.77; p=0.002), which was independent of treatment arm. This was supported by an OS advantage 21.95m vs 18.04m (HR 0.584; 95% CI 0.34 to 1.00; p=0.051). High RET expression did not predict an advantage of vandetanib use. Toxicity data will be presented.

Conclusions

The trial has shown that addition of vandetanib to fulvestrant does not improve PFS significantly. However, in the pre-planned exploratory analysis, high total RET expression was significantly associated with improved PFS, suggesting RET may predict tumour sensitivity to fulvestrant in AI resistant disease. This finding would require further validation.

Clinical trial identification

No editorial assistance was provided by a third party in the writing of the abstract.

Legal entity responsible for the study

Velindre University NHS Trust, Cardiff.

Funding

AstraZeneca, Cancer Research UK (CRUK).

Disclosure

T. Hickish: Full/Part-time employment, Medical Director: iQHealth Tech. D. Wheatley: Honoraria (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution): Lilly; Honoraria (institution): Novartis; Honoraria (institution): Amgen; Honoraria (institution): Daiichi Sankyo. All other authors have declared no conflicts of interest.

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Mini Oral - Breast cancer, metastatic Mini Oral session

Invited Discussant 282MO, 283MO and LBA20

Speakers
  • Laura Biganzoli (Prato, Italy)