Maritim Hall Proffered Paper session
Date
03.05.2019
Time
16:45 - 18:15
Location
Maritim Hall
Chairs
  • Giuseppe Curigliano (Milan, Italy)
  • Sibylle Loibl (Neu-Isenburg, Germany)
Best abstracts session (ID 44) Proffered Paper session

Session DOI (ID 865)

Lecture Time
16:45 - 16:45
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15
Best abstracts session (ID 44) Proffered Paper session

108O - Factors predicting relapse in early breast cancer patients with a pathological complete response after neoadjuvant therapy: Pooled analysis based on the GBG database (ID 712)

Presentation Number
108O
Lecture Time
16:45 - 17:00
Speakers
  • Jens Huober (Ulm, Germany)
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15

Abstract

Background

Although patients with a pathological complete response (pCR) after neoadjuvant chemotherapy have an excellent prognosis, some of them will eventually relapse. A better identification of patients with an increased risk of relapse despite a pCR can help selecting these patients for additional post-neoadjuvant treatment strategies. This retrospective analysis aimed to identify factors predicting relapse despite a pCR.

Methods

A total of 2188 patients with a pCR from five neoadjuvant trials (GeparTrio, GeparQuattro, GeparQuinto, GeparSixto and GeparSepto) were included. The pCR was defined as ypT0/ypTis ypN0. Primary endpoint was disease-free survival (DFS); secondary endpoints were distant DFS (DDFS) and overall survival (OS). The potential risk factors biological subtype, histological tumour type, grading, clinical cT and cN status, Ki-67, age, BMI, planned number of cycles of chemotherapy, menopausal status, clinical response after 2-4 cycles as well as study identification were included as covariates in multivariate Cox regression models. The two-sided significance level was set to α = 0.05.

Results

From 2188 evaluable patients 290 DFS, 197 DDFS and 130 OS events were observed. The median follow-up over all studies was 59 months. Location of first relapse was locoregional in 129, distant in 134 and both in 23 patients. 1217 patients were included in multivariate analyses. DFS was significantly different with regard to the cN status (cN+ vs cN0 hazard ratio (HR)=1.70; [95%CI 1.2-2.4]; p = 0.002); a trend for worse DFS was seen for lobular tumour type (lobular vs other HR = 1.91 [95%CI 0.9-4.0]; p = 0.076) and cT status (cT3/4 vs cT1 HR=1.61 [95%CI 1.0-2.7]; p = 0.064). Similar results were observed for DDFS. OS was significantly worse for cT3/4 tumours (cT3/4 vs cT1, HR = 2.48 [95%CI [1.1-5.7]; p = 0.030) and lobular tumour type (lobular vs other, HR = 2.85 [95%CI 1.1-7.2]; p = 0.026); a trend for worse OS was seen for cN + (cN+ vs cN0, HR = 1.67 95%CI [1.0-2.9]; p = 0.067).

Conclusions

Initial tumour load (tumour size and nodal status) and histological tumour type remained prognostic factors of long-term outcome even when a pCR was achieved.

Legal entity responsible for the study

GBG.

Funding

Has not received any funding.

Disclosure

A. Schneeweiss: Grants: Celgene, Roche, AbbVie, Molecular Partner; Personal fees: Roche, AstraZeneca, Celgene, Pfizer, Novartis, MSD, Tesaro, Lilly. C. Denkert: Shareholder and co-founder: Sividon Diagnostics; Honoraria/consultation: Teva, Novartis, Pfizer, Roche, Amgen, MSD, Daiichi, Celgene, AstraZeneca; Patent application: EP18209672 - Cancer immunotherapy. C. Hanusch: Personal fees: Novartis, Roche, Pfizer, Celgene, Amgen outside the submitted work. C. Jackisch: Personal fees: Roche, Celgene. M. Untch: Grants: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Janssen-Cilag, Lilly, MSD, Myriad Genetics, Pfizer, Mundipharma, Odonate, Puma Biotechnology, Riemser, Sanofi, Sividon Diagnostics, Teva, Roche. All other authors have declared no conflicts of interest.

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Best abstracts session (ID 44) Proffered Paper session

86O - Dose-dense adjuvant chemotherapy in early breast cancer: 15–year results of the phase III Mammella InterGruppo (MIG)-1 study (ID 475)

Presentation Number
86O
Lecture Time
17:00 - 17:15
Speakers
  • Eva Blondeaux (Genova, Italy)
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15

Abstract

Background

Dose dense adjuvant chemotherapy is the preferred treatment option in high-risk early breast cancer patients. We report the updated results of the MIG-1 study comparing the efficacy of fluorouracil, epirubicin and cyclophosphamide (FEC) regimen administered every 3 (FEC21) or every 2 (FEC14) weeks in early breast cancer patients.

Methods

In this Italian, open-label, multicentre phase III randomized trial, node positive and high-risk node negative breast cancer patients were randomised to receive 6 cycles of FEC21 or FEC14 (including support with a granulocyte colony-stimulating factor). The study primary end-point was overall survival (OS) and secondary end-point was event-free survival (EFS).

Results

From November 1992 to June 1997, 1214 patients were randomly assigned to receive FEC14 (n = 604) or FEC21 (n = 610). Median follow-up was 15.8 years. 15-year OS was 68% (95% CI 64-72) in FEC21 group and 71% (95% CI 67-75) in FEC14 group (HR = 1.13; 95% CI 0.92-1.40; p = 0.25). 15-year EFS was 43% (95% CI 37-48) in FEC21 group and 47% (95% CI 41-52) in FEC14 group (HR = 1.13; 95%CI 0.94-1.35; p = 0.19). In a pre-planned subgroup analysis, among patients with hormone receptor-negative tumors, 15-year OS was 65% (95% CI 58-72) in FEC21 group and 70% (95% CI 63-77) in FEC14 group (HR = 1.34; 95% CI 0.94-1.92; p = 0.11; pinteraction=0.25); 15-year EFS was 43% (95% CI 33-52) in FEC21 group and 58% (95% CI 48-67) in FEC14 group (HR = 1.47; 95% CI 1.08-2.01; p = 0.016; pinteraction=0.02). No differences between the two regimes was observed in patients with hormone receptor-positive tumors.

Conclusions

Updated results from the MIG1 study did not show a significant benefit with the use of dose-dense FEC chemotherapy in early breast cancer patients; EFS was prolonged with the use of dose-dense chemotherapy in patients with hormone receptor-negative disease.

Legal entity responsible for the study

Mammella InterGruppo (MIG).

Funding

Associazione Italiana per la Ricerca sul Cancro (AIRC).

Disclosure

M. Benasso: Honoraria: Merck, MSD, Bristol Myers Squibb (outside the submitted work). M. Lambertini: Consultant: Teva; Honoraria: Theramex outside the submitted work. L. Del Mastro: Personal fees: Ipsen, Pfizer, Eli Lilly, Eisai, Roche, Novartis, GlaxoSmithKline, Amgen, Teva, Takeda outside the submitted work. All other authors have declared no conflicts of interest.

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Best abstracts session (ID 44) Proffered Paper session

Invited discussant of 108O and 86O (ID 778)

Lecture Time
17:15 - 17:30
Speakers
  • Pier Franco Conte (Padova, Italy)
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15
Best abstracts session (ID 44) Proffered Paper session

LBA2 - Everolimus plus aromatase inhibitors vs aromatase inhibitors as maintenance therapy after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Final results of the phase III randomized MAIN-A trial (ID 672)

Presentation Number
LBA2
Lecture Time
17:30 - 17:45
Speakers
  • Valentina Guarneri (Padova, Italy)
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15

Abstract

Background

Hormonal therapy is the mainstay of treatment for HR+/HER2- metastatic breast cancer (MBC). However, patients (pts) presenting with aggressive disease are generally offered first-line chemotherapy (CT), followed by maintenance hormonal therapy. This study is aimed to evaluate whether maintenance everolimus (EVE) combined with aromatase inhibitors (AI) can prolong progression free survival (PFS) over AI alone in pts with disease control after first-line CT.

Methods

The Main-A trial is an investigator driven, randomized Phase III study. Postmenopausal pts achieving disease control (stable disease, partial response or complete response) after first-line CT were randomly assigned to EVE 10 mg po daily plus AI or to AI alone. Primary aim is PFS. We estimated a sample size of 54 pts per arm to detect an improvement from 6 to 11 months in the median PFS (Hazard Ratio 0.55).

Results

110 pts were randomized to EVE+AI (n = 52) or to AI (n = 58). Median age was 58 yrs. Fifty% of the pts had liver metastases. Median interval from the time of primary diagnosis to first metastasis was 11.2 mos (9.1 mos in the EVE+AI arm and 16.0 months in the AI arm). A total of 88 PFS events were recorded, 40 in the EVE+AI arm and 48 in the AI arm. Median PFS was 9.9 mos (95%CI: 7.4-13.8) in the EVE+AI arm vs 7.2 mos (95%CI: 4.7-10.9) in the AI arm (HR 0.764, 95%CI: 0.501-1.164). EVE dose reductions were reported for 28 pts. Treatment related adverse events (AEs) were reported for 45 (87%) pts in the EVE+AI arm and for 15 (26%) pts in the AI arm. In the EVE-AI arm, 16 pts discontinued EVE because of AEs or non-compliance. In the AI arm one pts only discontinued therapy because of AE. Most common G>/=2 AEs in the EVE-AI arm were stomatitis (19.2%), neutropenia (9.6%), interstitial pneumonia (7.7%) and skin toxicity (7.7%).

Conclusions

At our knowledge, this is the first randomized trial of maintenance endocrine therapy after CT for HR+/HER2- MBC. In these high risk MBC pts deemed suitable for first-line CT, maintenance therapy with AI resulted in a median PFS of 7.2 mos only. Adding EVE resulted in a 2.7 mos non significant PFS prolongation. No new safety signals emerged from this study.

Clinical trial identification

EudraCT: 2013-004153-24.

Legal entity responsible for the study

University of Padua, Department of Surgery, Oncology and Gastroenterology (DiSCOG).

Funding

Novartis.

Disclosure

V. Guarneri: Institutional research grant: Roche; Advisory boards: Eli Lilly, Roche, Novartis; Speaker’s bureau: Eli Lilly, Novartis. S. Cinieri: Honoraria: Eli Lilly. A. Frassoldati: Aadvisory board: Roche, Novartis; Sponsored lectures: Pfizer, Novartis, Lilly. C. Zamagni: Honoraria: Takeda, Pierre Fabre, Teva, Istituto Gentili; Consultant, advisory role: Roche, Eisai, Novaris, AstraZeneca, Pfizer, Pharmamar, Celgene, Lilly, Amgen, Tesaro, QuintilesIMS. P.F. Conte: Fees and honoraria for participation on advisory boards: Eli Lilly, Novartis, Roche, AstraZeneca. All other authors have declared no conflicts of interest.

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Best abstracts session (ID 44) Proffered Paper session

149O - Outcome and mutational landscape of patients with PIK3CA-mutated metastatic breast cancer (mBC) (ID 476)

Presentation Number
149O
Lecture Time
17:45 - 18:00
Speakers
  • Fernanda F. Mosele (Villejuif, France)
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15

Abstract

Background

In a recent study, α-selective PI3K inhibitor improved outcome in PIK3CA mutated HR+/Her2- mBC. Thus, to optimally position PI3K inhibitors, we have investigated the natural history of PIK3CA mutated BC.

Methods

649 patients with mBC from SAFIR02 trial (NCT02299999), with available mutational profile and clinical data were selected for outcome analysis. PIK3CA mutations were prospectively determined by NGS on metastatic sample. In addition, we looked at mutations enriched in PIK3CA mutant mBC (n = 629, whole exome sequencing).

Results

22% of patients (n = 143) harbor PIK3CA mutation in tumor sample. 29% (n = 104) of HR+/Her2- and 10% (n = 27) of TNBC tumors presented PIK3CA mutation (p < 0.001). HR+/Her2- PIK3CA mutated patients were less sensitive to chemotherapy (Odds ratio multivariate: 0.40; 95% CI [0.22-0.71]; p = 0.002). The median overall survival (OS) for patients with PIK3CA mutated HR+/Her2- mBC was 19.6 months vs. 23.5 for PIK3CA wt (p = 0.048) (HR multivariate: 1.44; 95% CI [1.02-2.03]; p = 0.039). PIK3CA mutated HR+/Her2- mBC were enriched in MAP3K1 mutation (17% vs. 5%, p = 0.0002), whereas PIK3CA wt tumors were enriched in GATA3 (25% vs. 14%, p = 0.022) or AKT1 mutations (11% vs. 3%, p = 0.008). In patients with HR+/Her2-/PIK3CA mutant mBC, the 24 months OS for MAP3K1 mutated patients was 14.7% vs. 45.5% for wt (p = 0.0059) (HR multivariate: 1.84; 95% CI [1.07-3.15]; p = 0.02). In TNBC, the median OS in patients with PIK3CA mutated tumors was 24.2 months vs. 14 for PIK3CA wt (p = 0.028). We further looked at the distribution of PIK3CA mutation in mTNBC, according to HR expression on 1ry tumor. 6% of patients with TNBC both on primary and metastasis presented a PIK3CA mutation (9/138), whereas 39% of patients with TNBC on metastasis and HR+ on 1ry tumor had PIK3CA mutation (14/36).

Conclusions

Patients with PIK3CA mutated HR+/Her2- mBC are less sensitive to chemotherapy and present a poor outcome. In this population, MAP3K1 mutations are more frequent and are associated with shorter survival. Patients with PIK3CA mutated TNBC have better survival. This could be explained by an enrichment of PIK3CA mutations in luminal BC who lost HR in the metastatic setting.

Editorial acknowledgement

Bojana Stefanovska.

Clinical trial identification

NCT02299999.

Legal entity responsible for the study

Unicancer/Gustave Roussy.

Funding

ARC, Breast Cancer res Foundation and French NCI.

Disclosure

C. Massard: Consultant/advisory fees: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion. F. André: Research grants and compensation to institution: Novartis, AZ, Daiichi, Roche, Lilly, Pfizer. All other authors have declared no conflicts of interest.

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Best abstracts session (ID 44) Proffered Paper session

Invited discussant of LBA and 149O (ID 779)

Lecture Time
18:00 - 18:15
Speakers
  • Miguel Martín (Madrid, Spain)
Location
Maritim Hall, MARITIM Hotel Berlin, Berlin, Germany
Date
03.05.2019
Time
16:45 - 18:15