- Laura Biganzoli (Prato, Italy)
- Carmen Criscitiello (Milan, Italy)
- Peter Kern (Essen, Germany)
177PD - Prospective, multicenter registry trial to evaluate the clinical feasibility of targeted axillary dissection (TAD) in patients (pts) with breast cancer (BC) and core biopsy proven axillary involvement (cN+) (ID 4132)
- Mattea Reinisch (Essen, Germany)
Abstract
Background
As part of de-escalating strategies of the axillary treatment in lymph node (LN) positive BC pts, TAD was introduced (Caudle et al., JCO 2016). Despite this very interesting approach, some important aspects regarding the clinical feasibility after neoadjuvant chemotherapy (NACT) were missing if a safe procedure was to be guaranteed. The correct evaluation of pathologic complete response (pCR) has a prognostic impact in high risk BC pts (Katherine, CreATE X). This study aimed to investigate the clinical feasibility of clip placement in positive axillary LNs followed by NACT and TAD in BC patients.
Methods
The Senta trial is a prospective, multicentric registry study (N = 598). Prior to NACT, pts with invasive BC received an ultrasound guided core biopsy with clip insertion into the suspicious axillary LN. After NACT, pts underwent axillary surgery according to the investigators discretion, with or without sentinel LN (SLN) biopsy. TAD included removal of the clipped LN and SLN biopsy (SLNB). The pathology of the clipped LN before and after NACT, other LNs, and the SLN were compared. The primary endpoint (EP) was the detection rate (DR) of the clipped LN after NACT. Secondary EP was the false negative rate (FNR) of TAD.
Results
Between January 2017 and October 2018, 598 cN+ BC pts from 50 different German breast units had biopsy proven axillary LN involvement and received clip insertion into the affected LN. The complete data set from 378 pts was available. After NACT, the clipped N was detected in 78.6% of the patients (target lymph node biopsy = TLNB), and 58.9% of the whole cohort received SLNB as well. The SLN and TLN were identical in 48.0%. An axillary dissection was performed overall in 68%. The FNR of TLNB was 8.0% (CI 95%, 3.0–12.0) for the whole cohort. TAD followed by axillary LN dissection had a FNR of 4.4% (2 of 45, CI 95%, 0.02–9.0).
Conclusions
Preliminary results demonstrated a high DR supporting the feasibility of this approach, however, the FNR of TAD (4.4%) was higher than reported earlier (FNR = 2.0%, Caudle et al.). This is of great importance for postneoadjuvant treatment decisions in case of non-pCR and should be discussed.
Clinical trial identification
NCT03102307; release date: April 5, 2017.
Legal entity responsible for the study
Kliniken Essen-Mitte.
Funding
Has not received any funding.
Disclosure
M. Reinisch: Honoraria (self): Pfizer, Novartis, Eli Lilly, Roche; Advisory / Consultancy: Roche, Daiichi Sankyo, Hexal, Eli Lilly, Novartis; Travel / Accommodation / Expenses: Pfizer, Celgene, Novartis. J. Heil: Advisory / Consultancy: Roche, Siemens Healthcare Diagnostics; Research grant / Funding (self): BARD; Honoraria (self): Roche, Siemens Healthcare Diagnostics, BARD; Travel / Accommodation / Expenses: Celgene. C. Seiberling: Travel / Accommodation / Expenses: Teva. C. Ankel: Advisory / Consultancy, Travel / Accommodation / Expenses: PFM medicals. V. Hanf: Honoraria (self): Novartis. J. Holtschmidt: Travel / Accommodation / Expenses: Roche. S. Kuemmel: Advisory / Consultancy: Genentech, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex, Daiichi Sankyo, Puma Biotechnology, PFM Medical, Pfizer, MSD Oncology; Travel / Accommodation / Expenses: Roche, Daiichi Sankyo. All other authors have declared no conflicts of interest.
178PD - Long-term results of the PACS 04 trial evaluating adjuvant epirubicin plus docetaxel in node-positive breast cancer and trastuzumab in the HER2-positive subgroup (ID 5429)
- Veronique D'Hondt (Montpellier, CEDEX 5, France)
Abstract
Background
Long term information on the risk/benefit ratio of currently available therapies remains crucial for treatment decisions. In the PACS04 phase III trial, patients (pts) with node-positive (N+) breast cancer (BC) were double-randomized to concomitant taxane-anthracycline versus standard FEC, as well as 1-year trastuzumab versus nill in the HER2+ subpopulation.
Methods
3009 pts (20% HER2+, 12% triple negative (TNBC) BC) were randomly assigned to receive 6 cycles of fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 (FEC) or epirubicin 75mg/m2 and docetaxel 75 mg/m2 (ED). Pts with HER2+ tumors were randomized to either trastuzumab (TRA) for one year, or observation (OBS). The primary endpoint was disease-free survival (DFS).
Results
After a median 115-month follow-up, DFS was not different in the ED compared to the FEC arm (70% vs 68% respectively, HR = 0.88 [95% CI: 0.77-1.01]; p = 0.064), nor was OS: 80% with FEC and 81% with ED (HR = 0.97 [95% CI: 0.81-1.16]; p = 0.729). Subgroup analysis suggested better DFS with ED in non-TNBC pts [HR = 0.82 (0.71-9.96) p = 0.02]. In the 528 pts with HER2+ BC, there was trend for a higher DFS in the TRA arm (68%; [95% CI: 61-74]) versus the OBS arm (60%; [95% CI: 54-66]); HR = 0.77 [95% CI:0.57-1.03]; p = 0.079 (intent to treat population). In the per protocol population, DFS, but not OS, was significantly higher in the TRA arm (HR: 0.69 [95%CI: 0.51-0.94]; p = 0.0156). ED led to more neurological and hematological toxicities (31% vs 11% febrile neutropenia) and led to 5 versus 1 treatment-related deaths. During follow-up, 75 pts developed a second non-breast primary cancer (43 with FEC and 32 with ED); 12 were hematologic malignancies (7 with FEC and 5 with ED). Long term cardiac deaths were rare (3 with FEC and 1 with ED).
Conclusions
This study did not show superiority of the concomitant anthracycline-taxane arm, which was more toxic in high-risk N+ BC pts. Long-term results of the HER2+ subpopulation are in line with the other adjuvant TRA trials but less striking probably due to lack of power. Long term cardiac toxicity and second primary cancer rate are similar to what has been reported by others.
Clinical trial identification
NCT00054587.
Legal entity responsible for the study
UNICANCER. 101 rue Tolbiac, 75013 Paris, France.
Funding
Roche, Ligue Nationale Contre le Cancer.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 177PD and 178PD (ID 6658)
- Peter Kern (Essen, Germany)
Q&A led by Discussant (ID 6659)
179PD - Tumor size and overall survival in a cohort of young (≤40 years), nodenegative, systemically untreated breast cancer patients; by the PARADIGM study group (ID 3790)
- Vincent De Jong (Amsterdam, Netherlands)
Abstract
Background
In the 1990s, the use of adjuvant systemic therapy was based on nodal involvement but not on tumor size, as was recommended in the Dutch breast cancer guidelines. Tumor size is an important prognostic variable in breast cancer, although this may not hold true for all molecular subtypes or patient ages. Here, we studied the prognostic value of tumor size for young (≤40 years at diagnosis), systemically untreated, node-negative (N0), breast cancer patients, and assessed whether for any given T-stage survival exceeds 90% at 20 years.
Methods
All female, breast cancer patients, ≤40 years at time of diagnosis (between 1989 and 2000), were selected from the Netherlands Cancer Registry. All lymph node-positive and systemically treated patients were excluded, resulting in a cohort of 2302 women. Clinico-pathological and follow-up data were collected from national databases, patient records, and the original pathology reports. Multivariate cox regression for overall survival was performed using T-stage (TNM 8.0), molecular subtype, and tumor grade (according to Nottingham Histologic Score) as covariates.
Results
Survival rates at 20-years are shown in Table. Median follow-up was 17 years. Only 1% had a T3 tumor and these patients were excluded from analysis. The 20-yr OS for the 96 (4%) T1a tumors was 81% (not shown). Women with T2 tumors had a significantly lower OS compared to women with T1a (HR 1.9 P = 0.024), T1b (HR 1.7 P = > 0.001) and T1c tumors (HR 1.31 P = 0.002), adjusted for tumor grade and molecular subtype. No OS data is shown for subgroups with less than 35 patients. 179PD Overall survival (OS; %) at 20 years by T-stage, molecular subtype and tumor grade (Gr)T1b T1c T2 All n OS n OS n OS n OS 359 73 1114 69 611 60 2302 68 ER+HER2- Gr 1 + 2 Gr 3 172 82 464 77 165 56 973 73 43 68 130 55 83 49 269 54 All 79 72 55 69 ER-HER2- Gr 1 + 2 Gr 3 6 - 31 - 27 - 70 65 31 - 205 73 158 66 417 68 All 61 71 63 68 HER2+ Gr 1 + 2 Gr 3 31 - 74 54 36 54 159 57 22 - 81 53 54 61 169 56 All 70 54 57 58
Conclusions
T-stage is associated with OS in this patient group. At 20 years follow-up, we found no T-stage with OS rates >90% in N0, systemically untreated patients, meaning that patients regardless of T-stage may benefit from some form of systemic treatment.
Legal entity responsible for the study
The PARADIGM study group.
Funding
The Netherlands Organization for Health Research and Development (ZonMW); A Sister’s Hope; De Vrienden van UMC Utrecht.
Disclosure
S.C. Linn: Research grant / Funding (self): Amgen; Research grant / Funding (self), unrestricted research grant SUBITO study (NCT02810743): Eurocept-pharmaceuticals; Research grant / Funding (institution), research grant NCT02810743 & olaparib;fulvestrant NCT00738777;advisory board olaparib breast cancer: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution), unrestricted research grant for NCT02285179 and study drug (taselisib): Genentech; Advisory / Consultancy, Member of the Scientific Advisory Board of Cergentis (unpaid): Cergentis; Advisory / Consultancy, scientific advisory board for Watson for Oncology (paid to institution): IBM; Research grant / Funding (institution), unrestricted research grant and study drug NCT03283384; research support biomarker study NCT02109913: Novartis; Advisory / Consultancy, Research grant / Funding (institution), scientific advisory board palbociclib; TEAM 2b through unrestricted research grant from Pfizer: Pfizer; Research grant / Funding (institution), Unrestricted research grant paid to institution for ABC study and study drug: Tesaro; Honoraria (institution), Fee for teaching paid to institution: Bayer. All other authors have declared no conflicts of interest.
180PD - Impact of chemotherapy-induced ovarian failure (CIOF) on disease-free survival (DFS) and overall survival (OS) in young women with early breast cancer (EBC) (ID 4332)
- Jenny Furlanetto (Neu-Isenburg, Germany)
Abstract
Background
Previous data has shown that chemotherapy (CT)-induced amenorrhea was associated with a better DFS and OS in premenopausal patients with EBC, regardless of the hormone-receptor status (Swain et al. NEJM 2010 ).
Methods
740 patients (pts) aged ≤45yrs treated with anthracycline/taxane-based CT for EBC from 4 German neo-/adjuvant trials were included. Centrally assessed estradiol and follicle-stimulating hormone (FSH) in paired blood samples collected at baseline and 4 weeks after the last therapy infusion were considered. CIOF was defined as estradiol <52.2 ng/L and FSH >12.4IU/l after CT for those pts with premenopausal hormone levels at baseline. 4-year DFS and OS (rate, hazard ratio (HR) and 95% confidence interval (CI)) overall and in subgroups by hormone-receptor status (positive, negative) and age (≤30, 31-35, 36-40, >40yrs) are presented.
Results
Median follow-up was 49.6 (range 48.8-50.3) months. 4-year DFS and OS rates as well as HR overall and in subgroups are presented in the Table below. Pts with CIOF had a better DFS compared to pts without CIOF (HR = 0.47, 95%CI 0.31-0.71). The DFS advantage was significant in pts with hormone-receptor positive (HR = 0.38, 95%CI 0.22-0.64) EBC. A trend towards a better OS was observed only for pts with hormone-receptor positive EBC (HR = 0.45, 95%CI 0.19-1.05). Within age groups, CIOF showed a statistically significant improvement in DFS only in women ≤30yrs (HR = 0.21, 95%CI 0.05-0.97). No statistically significant OS benefit was observed in any of the age groups. Only pts >40yrs showed a trend towards a better OS (HR = 0.35, 95%CI 0.11-1.16). 180PDDFS OS 4-year rate log rank p-value HR [95% CI] 4-year rate log rank p-value HR [95% CI] CIOF no CIOF CIOF no CIOF overall (n = 740) 84.4 65.0 <0.001 0.47 [0.31-0.71] 92.6 88.7 0.180 0.64 [0.33-1.23] hormone-receptor status negative (n = 315) 79.9 69.7 0.147 0.62 [0.32-1.19] 88.9 89.3 0.879 0.92 [0.32-2.62] positive (n = 425) 87.8 62.6 <0.001 0.38 [0.22-0.64] 95.5 88.7 0.059 0.45 [0.19-1.05] age (years) ≤30 (n = 62) 92.8 69.5 0.027 0.21 [0.05-0.97] 95.7 90.8 0.286 0.31 [0.03-3.00] 31-35 (n = 100) 80.4 59.9 0.099 0.49 [0.21-1.16] 92.2 96.3 0.945 1.06 [0.22-5.15] 36-40 (n = 205) 81.8 63.5 0.119 0.54 [0.25-1.18] 92.7 84.9 0.431 0.61 [0.17-2.13] >40 (n = 373) 85.7 65.0 0.207 0.53 [0.19-1.45] 92.4 81.3 0.072 0.35 [0.11-1.16]
Conclusions
Pts with CIOF after anthracycline/taxane-based CT for EBC show a better DFS, especially in women with hormone-receptor positive EBC or younger than 30 years. The improvement in DFS translates in a survival advantage in pts with hormone-receptor positive EBC.
Legal entity responsible for the study
German Breast Group (GBG).
Funding
The study was supported by Walter Schulz Stiftung.
Disclosure
A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD Oncology; Honoraria (self): Tesaro; Honoraria (self), Travel / Accommodation / Expenses: Lilly. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. M. Untch: Honoraria (institution), Non-remunerated activity/ies: Abbvie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH; Honoraria (institution), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution), Non-remunerated activity/ies: Janssen Cilag; Honoraria (institution), Non-remunerated activity/ies: Lilly; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genetics; Honoraria (institution), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies: Novartis. P.A. Fasching: Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Biontech; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): PUMA; Research grant / Funding (institution): Cepheid. F. Marmé: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Tesaro; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): PharmaMar; Honoraria (self): GenomicHealth; Honoraria (self): CureVac; Honoraria (self): EISAI; Honoraria (self): Clovis; Honoraria (self): Celgene. M. van Mackelenbergh: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Amgen. V. Müller: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgem; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Diichi-Sankyo; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Speaker Bureau / Expert testimony: Teva; Honoraria (self), Speaker Bureau / Expert testimony: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Nektar; Research grant / Funding (institution): Seattle Genetics. S. Loibl: Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Teva; Research grant / Funding (institution): Vifor; Research grant / Funding (institution): PRIME; Research grant / Funding (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. All other authors have declared no conflicts of interest.
181PD - Improved survival of older patients with advanced breast cancer due to an increase in systemic treatments – a population-based study (ID 1375)
- Nienke De Glas (Leiden, Netherlands)
Abstract
Background
The number of older patients with breast cancer is rapidly increasing. A previous study showed that in the Netherlands, between 1990 and 2005, survival of older patients with breast cancer did not improve in contrast to younger patients. In recent years, scientific evidence in the older age group has increased and specific guidelines for older women with breast cancer have been developed. The aim of this study was to assess recent survival outcomes of older patients with breast cancer compared to younger patients.
Methods
All patients with stage I-IV breast cancer between 2000 and 2017 were included from the Netherlands cancer registry. We assessed changes in treatments over time using logistic regression models. We calculated the changes in relative survival as proxy for breast cancer mortality, stratified by age and stage.
Results
We included 239,992 patients. Relative survival improved over time for patients in the youngest age-group for all stages. In patients aged 65-75 years, relative survival adjusted for tumour characteristics did not improve in stage I-II but did improve in stage III (RER 0.98, 95% C.I. 0.96-1.00, p = 0.046). Concurrently, was prescribed in an increasing proportion of patients aged 65-75 years (33.6% in 2000 to 52.7, p < 0.001). In patients aged 75 years or older, relative survival did not improve in patients with stage I/II or stage III disease, nor did treatment strategies change.
Conclusions
This study shows that over time, the relative survival of patients aged 65-75 years with advanced breast cancer has improved, and concurrently, prescription of systemic treatment increased. These data suggest that older patients with advanced breast cancer do benefit from adjuvant systemic treatment. In order to further improve survival of patients >75 as well, future studies should focus on individualizing treatments based on concomitant comorbidity, geriatric parameters and the risk toxicity of treatments.
Legal entity responsible for the study
Leiden University Medical Center, Department of Medical Oncology, Geriatric Oncology Research Group.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 179PD, 180PD and 181PD (ID 6660)
- Laura Biganzoli (Prato, Italy)
Q&A led by Discussant (ID 6661)
182PD - Utility of the CPS+EG scoring system in triple-negative breast cancer treated with neoadjuvant chemotherapy (ID 4042)
- Frederik Marmé (Mannheim, Germany)
Abstract
Background
Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with superior disease free (DFS) and overall survival (OS). This association is strongest in triple-negative breast cancer (TNBC). The CPS+EG system, based on pre-treatment clinical (CS) and post-treatment pathologic stage (PS), grade and estrogen receptor status, leads to a refined estimate of prognosis after NACT in all comers and HR+/HER2- (Marmé et al Eur J Cancer 2016). Here we investigate if CPS+EG scoring provides a superior estimate of prognosis in TNBC after NACT to select patients (pts) for post-neoadjuvant therapy.
Methods
We calculated the CPS+EG score for 1795 pts with TNBC from 9 prospective German trials. Pts with missing variables were excluded. 5-year DFS estimates were calculated using the Kaplan Meier method.
Results
Pts who achieved a pCR had a 5-year DFS of 86% (n = 822, 45.8%), whereas pts with residual stage I had a 5-yr DFS of 77.5% (n = 383; 21.3%). CPS+EG score was unable to identify non-pCR pts with a sufficiently good prognosis, to avoid post neoadjuvant therapy. The best prognostic CPS+EG groups (score 1/2) in non-pCR pts had a 5-year DFS of 77.5% and 74.4%, respectively (n = 362; 37.2%). CPS+EG identified a small group (n = 26; 3.2%) at high risk of recurrence despite pCR, mainly based on initial stage (CS+EG score > 3; 5-year DFS 61.4%) that might benefit from additional treatment. However, prognosis of pts with a CPS+EG score of 3 (5-year DFS: 64%), could be further discriminated by pCR (5-year DFS: 83.9% vs 49.7%). Detailed results are presented in the Table. 182PDpathologic stage: All patients CPS+EG: All patients CPS+EG: non-pCR patients CPS+EG: pCR patients PS (N = 1795) 5-year DFS rate* 95% CI N % CPS-EG (N = 1795) 5-year DFS rate* 95% CI N % CPS-EG (N = 973) 5-year DFS rate* 95% CI N % CPS-EG (N = 822) 5-year DFS rate* 95% CI N % 0 0.86 0.84 0.89 822 45.8 0 0.00 0.00 0.00 0 0 0 0.00 0.00 0.00 0 0 0 0.00 0.00 0.00 0 0 I 0.78 0.73 0.82 383 21.3 1 0.83 0.77 0.89 189 10.5 1 0.78 0.68 0.87 88 9.0 1 0.88 0.81 0.95 101 12.3 IIA 0.49 0.43 0.55 292 16.3 2 0.84 0.81 0.86 761 42.4 2 0.74 0.69 0.80 274 28.2 2 0.89 0.86 0.92 487 59.2 IIB 0.39 0.29 0.50 89 5.0 3 0.64 0.59 0.69 497 27.7 3 0.50 0.44 0.56 289 29.7 3 0.84 0.78 0.89 208 25.3 IIIA 0.24 0.15 0.33 109 6.1 4 0.41 0.34 0.47 252 14.0 4 0.38 0.32 0.45 226 23.2 4 0.61 0.42 0.81 26 3.2 IIIB 0.19 0.02 0.36 21 1.2 5 0.16 0.07 0.25 71 4.0 5 0.16 0.07 0.25 71 7.3 5 0.00 0.00 0.00 0 0.0 IIIC 0.12 0.04 0.20 79 4.4 6 0.00 0.00 0.00 25 1.4 6 0.00 0.00 0.00 25 2.6 6 0.00 0.00 0.00 0 0.0
Conclusions
pCR remains the strongest and most clinically useful prognostic factor after NACT in TNBC. The CPS-EG score does not add additional information beyond pCR and ypT/N staging in TNBC patients. Other factors than those used beyond staging might be needed in TNBC.
Legal entity responsible for the study
GBG.
Funding
Has not received any funding.
Disclosure
F. Marmé: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Tesaro; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): PharmaMar; Honoraria (self): GenomicHealth; Honoraria (self): CureVac; Honoraria (self): EISAI; Honoraria (self): Clovis; Honoraria (self): Celgene. P.A. Fasching: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BionTech; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): Puma; Research grant / Funding (institution): Cepheid. A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Honoraria (self), Travel / Accommodation / Expenses: Pfizer. J. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Genomic Health; Honoraria (self): MSD Oncology; Honoraria (self): Myriad Genetics; Honoraria (self): Novratis/Pfizer; Honoraria (self): Pfizer; Honoraria (self): Rpche; Honoraria (self): Sonoscape. J. Huober: Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Hexal; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self): Abbie. C. Jackisch: Travel / Accommodation / Expenses: Celgene; Honoraria (self): Roche. T. Link: Honoraria (self): Amgen; Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: PharmaMar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche. K. Rhiem: Honoraria (self): Tesaro; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Lilly; Honoraria (self): AstraZeneca. H. Tesch: Honoraria (self): Vifor; Honoraria (self): Roche; Honoraria (self): Amgen. S. Loibl: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Teva; Research grant / Funding (institution): Vifor; Research grant / Funding (institution): PRIME; Research grant / Funding (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. 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), Non-remunerated activity/ies: Celgene GmbH; Honoraria (self): BMS; Honoraria (self), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (self), Non-remunerated activity/ies: Eisai GmbH; Honoraria (self), Non-remunerated activity/ies: Janssen Cilag; Honoraria (self), Non-remunerated activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (self), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (self), Non-remunerated activity/ies: Lilly; 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: Novartis; Honoraria (self), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (self), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH. All other authors have declared no conflicts of interest.
183PD - Neoadjuvant endocrine therapy with palbociclib in patients with high-risk breast cancer (ID 4001)
- Per Eystein Lønning (Bergen, Norway)
Abstract
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.
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.
184PD - Neoadjuvant olaparib monotherapy in primary triple negative breast cancer (ID 3933)
- Hans P. Eikesdal (Bergen, Norway)
Abstract
Background
Neoadjuvant treatment of triple negative breast cancer (TNBC) in general implies different chemotherapy regimens administered in sequence. PARP inhibitors like olaparib have revealed clinical benefit in TNBC harboring BRCA germline mutations, but were ineffective when tested as monotherapy for BRCA WT metastatic breast cancer. While combining a PARP inhibitor with chemotherapy may be beneficial, such therapy is limited by bone marrow toxicity.
Methods
In the phase 2 PETREMAC trial (NCT02624973), we assessed the efficacy of primary olaparib monotherapy for 10 weeks, followed by chemotherapy, in TNBC (T > 2 cm). Tumor biopsies and blood leucocytes for targeted DNA sequencing of 360 cancer-related genes were collected prior to therapy and after 10 weeks on olaparib.
Results
31 patients with TNBC were included (mean tumor size 59 mm; range 33-97). Olaparib monotherapy was well tolerated, yielding a clinical CR in 5 and a PR in 15 patients (all-over objective response rate; ORR 64%). Olaparib had no major impact on subsequent chemotherapy toxicity. The average pretreatment mutation rate was 3.3 indels/point mutations per tumor with no differences in mutation burden recorded between responders and non-responders or BRCA carriers vs. non-carriers. Among five patients harboring pathogenic BRCA1/2 mutations (4 germline, 1 somatic) all responded to olaparib, and n = 3/5 obtained pathological complete response. Interestingly, mutations in genes associated with DNA damage repair (ATRX, BRCA1/2, EMSY, MSH6, PARP10, PPM1D) occurred in n = 9/20 olaparib responders, but in none of the 11 non-responders (p = 0.011). Non-responders were characterized by mutations in oncogenic pathways (PIK3CA, AKT1, KRAS, IGF2R, NF2 and TGFBR2) in 7 out of 11 tumors (P = 0.00013). No significant association was observed between TP53 mutations (recorded in 23/31 tumors) and response to olaparib. Targeted DNA sequencing is ongoing for biopsies taken after 10 weeks of olaparib monotherapy; the results will be presented.
Conclusions
Olaparib yielded a high response rate when administered to treatment-naïve, large TNBC, indicating a potential role in sequential neoadjuvant therapy, for patients both with and without BRCA1/2 germline mutations.
Clinical trial identification
NCT02624973; 2015-002816-34.
Legal entity responsible for the study
Haukeland University Hospital, Bergen, Norway.
Funding
Det Regionale Samarbeidsorganet/Helse Vest, AstraZeneca.
Disclosure
H.P. Eikesdal: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; 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): Brysol-Mayers-Squibb; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Abbvie. E.S. Blix: Honoraria (self): Pfizer. B. Gilje: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Astellas Oncology; Research grant / Funding (institution): Celgene; 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): AstraZeneca; Honoraria (self): Roche. S. Knappskog: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Licensing / Royalties: Patent EP2389450 A1,Patent WO 2012/010661.. P.E. Lønning: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Laboratorios Farmaceuticos Rovi; Licensing / Royalties: Cytovation. All other authors have declared no conflicts of interest.
185PD - Immunological differences between immune-rich estrogen receptor-positive and -negative breast cancers (ID 1804)
- Tess O'Meara (New Haven, United States of America)
Abstract
Background
A subset of estrogen receptor-positive (ER+) breast cancers have significant tumor infiltrating lymphocytes (TILs), similar to triple-negative breast cancer (TNBC). We examined differences in the immune microenvironment of immune-rich ER+ and immune-rich TNBC to find out if similar or different immunotherapy strategies are appropriate for these distinct disease types.
Methods
ER+/HER2-negative and TNBC cases were obtained from The Cancer Genome Atlas (TCGA) (n = 818 RNA Seq) and METABRIC (n = 1465 microarray). An immune gene expression score, as surrogate for TILs, was calculated for each case (Danaher et al). Signature scores were correlated with histologic TILs (R = 0.44, p < 0.001) for available cases. All cases in the top 25% of signature scores were considered immune-rich. We compared 22 immune cell populations between immune-rich TNBC (n = 86) and ER + (n=119) using CIBERSORT (Student’s t-test, FDR adjusted). We examined differential expression of 770 immune-related genes and 137 immuno-oncology (IO) drug targets. Macrophage abundance was measured by quantitative immunofluorescence (QIF) using pan-macrophage marker CD68 in 169 TNBC and 87 ER+ FFPE tissues.
Results
In TCGA and METABRIC, CIBERSORT showed more M0 (p = 0.015, p = 0.0043) and M1 macrophages (p = 9.4e-08, p = 6.24e-11) in immune-rich TNBC compared to ER+. Mast cells (p = 0.0093, p = 4.09e-15) and M2 macrophages (p = 4.4e-05, p = 0.053) were more abundant in immune-rich ER+. QIF confirmed higher macrophage content in TNBC (p = 0.0001). In both datasets, 36 IO targets were higher expressed in TNBC and 15 in ER+ cases (Table). Notably, coordinated high expression of TGFb pathway members TGFb3, TGFb-R2, and LRRC32 was seen in ER+ cancers and correlated positively with M2 and negatively with M1 macrophage content across all cases. 185PDPotential ER+ Immuno- Oncology Targets TNBC Mean Expression ER+ Mean Expression Fold-Change Mean Expression p-value FDR-adjusted IL6ST 2,717 11,815 4.35 5.13E-21 2.32E-19 TGF-b3 2,085 4,745 2.28 1.32E-24 8.97E-23 CXCR1 (IL-8 receptor A) 439 988 2.25 1.04E-09 7.46E-09 CSF3R 1,050 2,025 1.93 8.46E-12 7.67E-11 RORC 1,008 1,855 1.84 3.65E-08 2.26E-07 ADORA2A 2,163 3,442 1.59 6.18E-08 3.65E-07 LRRC32 (TGFb activator) 7,549 11,152 1.48 1.09E-07 5.31E-07 TLR3 880 1,300 1.48 1.65E-05 5.92E-05 CXCL12 1,055 1,535 1.45 8.44E-05 2.53E-04 CLEC14A 492 705 1.43 2.68E-05 9.11E-05 TGFb-R2 7,559 9,845 1.30 2.08E-04 5.90E-04 TNFSF14 799 872 1.09 2.94E-03 6.89E-03 MICA 349 374 1.07 7.54E-03 1.51E-29 NLRP3 3,015 3,145 1.04 3.12E-03 7.20E-03 JAK1 12,683 13,058 1.03 0.019 0.035
Conclusions
IO drugs targeting TGFb, M2 macrophages and mast cells are attractive therapeutic candidates in immune-rich ER+ breast cancer based on the expression characteristics of these targets.
Legal entity responsible for the study
The authors.
Funding
Howard Hughes Medical Institute Medical Fellows Grant.
Disclosure
V. Pelenkanou: Full / Part-time employment: Sanofi, US. D. Rimm: Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Agendia; Advisory / Consultancy: Biocept; Advisory / Consultancy: BMS; Advisory / Consultancy: Cell Signaling Technology; Advisory / Consultancy, Research grant / Funding (institution): Cepheid; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: GSK; Advisory / Consultancy: InVicro/Konica/Minolta; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): NanoString; Advisory / Consultancy, Research grant / Funding (institution): Perkin Elmer; Advisory / Consultancy: PAIGE.AI; Advisory / Consultancy, Research grant / Funding (institution): Ventana; Advisory / Consultancy, Research grant / Funding (institution): Ultivue; Shareholder / Stockholder / Stock options: PixelGear; Research grant / Funding (institution): Navigate/Novartis; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Lilly. L. Pusztai: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Almac. All other authors have declared no conflicts of interest.
Invited Discussant 182PD, 183PD, 184PD and 185PD (ID 6662)
- Carmen Criscitiello (Milan, Italy)