V. Mueller (Hamburg, Germany)
UKE Universitätsklinikum Hamburg-Eppendorf KMTZAuthor Of 1 Presentation
HER2 targeting agents for treatment of HER2+ breast cancer with brain mets (ID 12)
Presenter Of 1 Presentation
HER2 targeting agents for treatment of HER2+ breast cancer with brain mets (ID 12)
Moderator Of 1 Session
Author Of 2 Presentations
- J. Furlanetto (Neu-Isenburg, Germany)
- M. Untch (Berlin, Germany)
- B. Sinn (Berlin, Germany)
- B. Lederer (Neu-Isenburg, Germany)
- A. Schneeweiss (Heidelberg, Germany)
- V. Mueller (Hamburg, Germany)
- M. Van Mackelenbergh (Kiel, Germany)
- E. Stickeler (Aachen, Germany)
- P. Fasching (Erlangen, Germany)
- C. Schem (Hamburg, Germany)
- T. Karn (Frankfurt am Main, Germany)
- F. Marmé (Mannheim, Germany)
- V. Nekljudova (Neu-Isenburg, Germany)
- S. Loibl (Neu-Isenburg, Germany)
17P - Impact of body mass index (BMI) on prognostic and predictive value of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC): a pooled analysis of six neoadjuvant trials.
Abstract
Background
Obesity is associated with T-cell dysfunction and reduced antitumor immune response. In TNBC, high sTILs seem to predict pathologic complete response (pCR) and favorable prognosis only in normal weight patients (Desmedt et al. Cancer Res 2020).
Methods
TNBC patients, who received anthracycline-taxane-based chemotherapy in GeparDuo, GeparTrio, GeparQuinto, GeparSixto, GeparSepto, and GeparOcto, with available BMI and pretreatment sTILs (centrally assessed) were considered. Patients with BMI <18.5 kg/m2 were excluded. Associations between BMI (normal weight, 18.5-<25 vs overweight/obese ≥25 kg/m2), sTILs (high ≥30% vs low <30) and pCR were assessed using Fisher`s exact test; between sTILs (continuous, dichtomized) and pCR (ypT0/is ypN0) according to BMI and interaction BMI*sTILs by logistic regression, between sTILs and disease-free survival (DFS) according to BMI and interaction BMI*sTILs by Cox regression.
Results
Of 1288 patients, 49.8% were normal weight, 50.2% overweight/obese; median age was 47 [21-78] vs 50 [21-76] years (p<0.001), cT3-4 12.0% vs 16.6% (p=0.021) and N+ 32.7% vs 37.0% (p=0.125). Normal weight patients had a higher pCR than overweight/obese patients (47.2% vs 39.9% p=0.009). Median sTILs was 30%, 50.4% of patients had high sTILs (normal weight 50.2% vs overweight/obese 50.6%, p=0.868). Higher level of sTILs was predictive for pCR both in normal weight (sTILs continuous OR 1.10, 95%CI 1.03-1.17, p=0.002) and in overweight/obese patients (OR 1.15, 95%CI 1.08-1.22, p<0.001). Interaction BMI*sTILs, p=0.302. Results were similar for dichotomized sTILs. Median follow-up was 54.7 months. Each 10% increase in sTILs was associated with an 11% reduction in the risk of a DFS event in normal weight (HR 0.89, 95%CI 0.82-0.95, p=0.001) and 8% in overweight/obese patients (HR 0.92, 95%CI 0.87-0.99, p=0.017). Interaction TILs*BMI, p=0.366.
Conclusions
Our results do not confirm differences in the predictive and prognostic role of sTILs according to BMI in TNBC as described previously. A joint analysis to explore the source of observed heterogeneity is planned.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Denkert: Research grant/Funding (self): European Commission H2020; Research grant/Funding (self): German Cancer Aid Translational Oncology; Honoraria (self): Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Molecular Health; Research grant/Funding (self): Myriad; Honoraria (self): Merck, Sividon diagnostics; Licensing/Royalties, patent VMScope digital pathology software with royalties paid: patent VMScope digital pathology software; Licensing/Royalties, cancer immunotherapy pending: patent WO2020109570A1; Licensing/Royalties, therapy response issued: patent WO2015114146A1 and WO2010076322A1. M. Untch: Honoraria (self), Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: Amgen GmbH; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self): BMS; Honoraria (self), Non-remunerated activity/ies: Celgene GmbH; Honoraria (self), Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self), Non-remunerated activity/ies: Eisai GmbH; Honoraria (self): Lilly Deutschland; Honoraria (self), Non-remunerated activity/ies: Lilly Int.; Honoraria (self), Non-remunerated activity/ies: MSD Merck; Honoraria (self), Non-remunerated activity/ies: Mundipharma; Honoraria (self), Non-remunerated activity/ies: Myriad Genetics; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (self), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (self): PUMA Biotechnology; Honoraria (self), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (self), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (self), Non-remunerated activity/ies: Teva Pharmaceuticals Ind Ltd.; Honoraria (self), Non-remunerated activity/ies: Novartis, Clovis Oncology; Honoraria (self): Pierre Fabre, Seatlle Genetics. A. Schneeweiss: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Research grant/Funding (self): AbbVie; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Research grant/Funding (self), Medical writing grant: Roche. V. Mueller: Speaker Bureau/Expert testimony: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seagen, Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Nektar; Advisory/Consultancy: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro and Nektar; Research grant/Funding (institution): Novartis, Roche, Seattle Genetics, Genentech. M. van Mackelenbergh: Honoraria (self): Amgen, AstraZeneca, Genomic Health, Mylan, Novartis, Pfizer, Pierre Fabre, Roche. P.A. Fasching: Honoraria (self): Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seattle Genetics, Roche, Hexal; Research grant/Funding (self): Biontech, Cepheid. F. Marmé: Research grant/Funding (self): AstraZeneca; Honoraria (self): AstraZeneca, MSD, Clovis, GSK/Tesaro, Pfizer, Novartis, Lilly, Roche, Celgene, Seagen, Myriad, PharmaMar, Eisai, Janssen-Cilag. S. Loibl: Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards: Abbie, Celgene; Honoraria (institution), honorario for lectures: PriME/Medscape; Honoraria (self): Chugai; Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to: Lilly; Advisory/Consultancy, advisor honorarium paid to institute: BMS, Puma; Research grant/Funding (institution): Immunomedics; Honoraria (institution), Research grant/Funding (institution), honorarium for lectures and ad: AstraZeneca, Amgen, Novartis, Pfizer; Honoraria (institution), honorarium for lectures and ad: Pierre Fabre, Merck; Honoraria (institution), advisor honorarium paid to institute: EirGenix; Honoraria (institution), Research grant/Funding (institution), grant and honorarium paid to: Roche; Honoraria (institution): Seagen; Licensing/Royalties, pending: EP14153692.0. All other authors have declared no conflicts of interest.
98P - Final results from AVANTI, a multicentre German observational study of 1st-line bevacizumab (BEV) + chemotherapy (CT) in >2000 patients (pts) with advanced breast cancer (aBC)
Abstract
Background
In Europe, BEV is approved in combination with paclitaxel (PAC) or capecitabine (CAP) as 1st-line therapy for HER2-negative aBC. AVANTI (ML22452) assessed safety, effectiveness and pt-reported outcomes (EORTC QLQ-C30) with these regimens in German routine oncology practice.
Methods
Eligible pts had HER2-negative aBC, no BEV contraindications and had received no prior CT for aBC. CT schedule, diagnostics and follow-up visits were at the physician’s discretion. Data were collected for 1 y after starting BEV, then every 6 mo for 1.5 y (max follow-up: 2.5 y). Treatment satisfaction was rated by pts and physicians. Subgroup analysis was prespecified in clinically relevant subgroups, including triple-negative breast cancer (TNBC).
Results
Between 1 Nov 2009 and 30 Apr 2016, 2065 eligible pts at 346 centres received ≥1 dose of BEV with PAC (n=1821) or CAP (n=295); 51 switched CT and were analysed in both subgroups. Data cut-off for the final analysis was 3 Feb 2020. Median age was 60 y, 21% had TNBC, 56% prior (neo)adjuvant CT and 29% de novo metastatic disease. Pts receiving BEV + CAP were less likely to have de novo disease and more likely to have TNBC, age ≥60 y and prior CT and endocrine therapy (ET). The median treatment duration was 6.0 mo (95% CI 5.6–6.3) for BEV and 4.2 mo (4.0–4.2) for CT. Overall (complete or partial) response rate was 49% (95% CI 46–51%). Median PFS was 12.6 (95% CI 11.9–13.2) mo (12.8 with BEV + PAC, 10.5 with BEV + CAP); median OS was 23.9 (22.2–25.1) mo. PFS and OS were worse in pts with TNBC, prior CT or prior ET (Table). Grade 3/4 AEs were reported in 27% of pts and led to treatment discontinuation in 15%. Treatment satisfaction was rated as good or better by 304/394 (77%) responding pts at week 54 and in 1393/2065 pts (67%) by physicians across the study. aUnknown in 127 pts. CI = confidence interval; HR = hazard ratio; OS = overall survival; PFS = progression-free survival.
Subgroup PFS OS Median, mo HR (95% CI) Median, mo HR (95% CI) Baseline hypertension Hypertensive v normotensive 13.6 v 11.9 0.88 (0.77–1.00) 25.1 v 23.2 0.88 (0.76–1.01) TNBCa Yes v no 10.3 v 12.9 1.44 (1.24–1.67) 16.8 v 25.2 1.53 (1.30–1.80) Age ≥60 v <60 y 12.8 v 12.3 1.09 (0.96–1.23) 21.9 v 25.4 1.26 (1.11–1.44) Metastatic sites ≥3 v <3 11.6 v 12.8 1.06 (0.88–1.28) 19.3 v 24.9 1.15 (0.96–1.39) Prior anthracycline/ taxane Yes v no 11.5 v 14.3 1.32 (1.16–1.50) 20.8 v 27.4 1.25 (1.09–1.43) Prior ET Yes v no 10.7 v 13.2 1.56 (1.33–1.82) 17.6 v 25.1 1.56 (1.33–1.82)
Conclusions
Final results from AVANTI show median PFS of 12.6 mo and a safety profile consistent with phase III experience.
Clinical trial identification
ML22452, 13th May 2015.
Editorial acknowledgement
Medical writing assistance: Jennifer Kelly (Medi-Kelsey Ltd.).
Legal entity responsible for the study
Roche Pharma AG.
Funding
Roche Pharma AG.
Disclosure
V. Mueller: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Teva; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Hexal; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: ClinSol; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Nektar; Research grant/Funding (institution): Genentech. O. Hoffmann: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Riemser Pharma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Hexal. A-K. Sommer: Full/Part-time employment: Roche Pharma AG; Shareholder/Stockholder/Stock options: Roche. A. Schneeweiss: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Research grant/Funding (institution): AbbVie. All other authors have declared no conflicts of interest.
Presenter Of 1 Presentation
98P - Final results from AVANTI, a multicentre German observational study of 1st-line bevacizumab (BEV) + chemotherapy (CT) in >2000 patients (pts) with advanced breast cancer (aBC)
Abstract
Background
In Europe, BEV is approved in combination with paclitaxel (PAC) or capecitabine (CAP) as 1st-line therapy for HER2-negative aBC. AVANTI (ML22452) assessed safety, effectiveness and pt-reported outcomes (EORTC QLQ-C30) with these regimens in German routine oncology practice.
Methods
Eligible pts had HER2-negative aBC, no BEV contraindications and had received no prior CT for aBC. CT schedule, diagnostics and follow-up visits were at the physician’s discretion. Data were collected for 1 y after starting BEV, then every 6 mo for 1.5 y (max follow-up: 2.5 y). Treatment satisfaction was rated by pts and physicians. Subgroup analysis was prespecified in clinically relevant subgroups, including triple-negative breast cancer (TNBC).
Results
Between 1 Nov 2009 and 30 Apr 2016, 2065 eligible pts at 346 centres received ≥1 dose of BEV with PAC (n=1821) or CAP (n=295); 51 switched CT and were analysed in both subgroups. Data cut-off for the final analysis was 3 Feb 2020. Median age was 60 y, 21% had TNBC, 56% prior (neo)adjuvant CT and 29% de novo metastatic disease. Pts receiving BEV + CAP were less likely to have de novo disease and more likely to have TNBC, age ≥60 y and prior CT and endocrine therapy (ET). The median treatment duration was 6.0 mo (95% CI 5.6–6.3) for BEV and 4.2 mo (4.0–4.2) for CT. Overall (complete or partial) response rate was 49% (95% CI 46–51%). Median PFS was 12.6 (95% CI 11.9–13.2) mo (12.8 with BEV + PAC, 10.5 with BEV + CAP); median OS was 23.9 (22.2–25.1) mo. PFS and OS were worse in pts with TNBC, prior CT or prior ET (Table). Grade 3/4 AEs were reported in 27% of pts and led to treatment discontinuation in 15%. Treatment satisfaction was rated as good or better by 304/394 (77%) responding pts at week 54 and in 1393/2065 pts (67%) by physicians across the study. aUnknown in 127 pts. CI = confidence interval; HR = hazard ratio; OS = overall survival; PFS = progression-free survival.
Subgroup PFS OS Median, mo HR (95% CI) Median, mo HR (95% CI) Baseline hypertension Hypertensive v normotensive 13.6 v 11.9 0.88 (0.77–1.00) 25.1 v 23.2 0.88 (0.76–1.01) TNBCa Yes v no 10.3 v 12.9 1.44 (1.24–1.67) 16.8 v 25.2 1.53 (1.30–1.80) Age ≥60 v <60 y 12.8 v 12.3 1.09 (0.96–1.23) 21.9 v 25.4 1.26 (1.11–1.44) Metastatic sites ≥3 v <3 11.6 v 12.8 1.06 (0.88–1.28) 19.3 v 24.9 1.15 (0.96–1.39) Prior anthracycline/ taxane Yes v no 11.5 v 14.3 1.32 (1.16–1.50) 20.8 v 27.4 1.25 (1.09–1.43) Prior ET Yes v no 10.7 v 13.2 1.56 (1.33–1.82) 17.6 v 25.1 1.56 (1.33–1.82)
Conclusions
Final results from AVANTI show median PFS of 12.6 mo and a safety profile consistent with phase III experience.
Clinical trial identification
ML22452, 13th May 2015.
Editorial acknowledgement
Medical writing assistance: Jennifer Kelly (Medi-Kelsey Ltd.).
Legal entity responsible for the study
Roche Pharma AG.
Funding
Roche Pharma AG.
Disclosure
V. Mueller: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Teva; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Hexal; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: ClinSol; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Nektar; Research grant/Funding (institution): Genentech. O. Hoffmann: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Riemser Pharma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Hexal. A-K. Sommer: Full/Part-time employment: Roche Pharma AG; Shareholder/Stockholder/Stock options: Roche. A. Schneeweiss: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Research grant/Funding (institution): AbbVie. All other authors have declared no conflicts of interest.