Displaying One Session
- Hope S. Rugo (San Francisco, CA, United States of America)
- Prudence Francis (Melbourne, VIC, Australia)
- Shaheenah Dawood (Dubai, United Arab Emirates)
Open & welcome
- Hope S. Rugo (San Francisco, CA, United States of America)
LBA13 - Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial
- Giampaolo Bianchini (Milan, Italy)
Abstract
Background
NeoTRIP, randomized 280 pts to 8 cycles of nab-paclitaxel/carbo (CT) or with atezolizumab (CT/A). 260 pts were evaluable for pCR as Per-Protocol Population.
Methods
We collected samples at baseline (n=260/260; 100%), on day 1 cycle 2 (d1c2) (n=228/260; 87.7%], and at surgery (SX) [n=231/260; 88.8%]. We assessed stromal and intratumoral TILs (sTILs, iTILs), and PD-L1 expression (SP142) on immune (IC) and tumor (TC) cells, their dynamics and association with pCR. We also aim to validate sTILs≥40% at d1c2 as predictive of pCR (Bianchini G ASCO 2020).
Results
Baseline PD-L1 IC was balanced (IC0 43.4%; IC1 37.6%; IC2/3 18.5%), but sTILs and iTILs were higher in CT arm (p=0.046, p=0.005). All baseline biomarkers were significantly associated with pCR in CT/A, but only PD-L1 was in CT arm. Considering log PD-L1 IC (to correct skewness) as continuous variable, OR were 3.42 [1.93-6.07] (p=0.00003) and 1.51 [1.04-2.21], (p=0.032) in CT/A and CT, respectively (interaction p=0.02). pCR for CT/A vs CT (and ΔpCR) by PD-L1 IC groups were 87.0% vs 72.0% [Δ15%] (IC2/3), 56.2% vs 44.0% [Δ12.2%] (IC1) and 35.1% vs 41.1% [Δ-6.0%] (IC0). After 1 cycle of treatment (d1c2), tumor cells were not found in 28.8% (CT/A) and 13.6% (CT) (p=0.003), which was predictive of pCR (78.2% vs 42.5%, p<0.0001). TILs increased at d1c2 in both arms (p<0.0001). PD-L1 IC+ did however increase from 45.4% to 74.7% in CT/A (p=0.03) (65.8% change to pos), but decreased from 52.7% to 37.9% in CT (p=0.0001) (44.0% change to neg). In CT/A, also PD-L1 TC+ increased for 2.7% to 36.5%. In both arms, sTILs at d1c2 were more informative than baseline sTILs and ΔTILs, e.g. in CT/A, sTILs≥40% had 71.4% pCR (OR 6.38 [2.24-20.9], p=0.0007). Conversion rate of PD-L1 IC baseline to surgery (SX) was 42.9% (- to + 28.6% and + to – 14.3%) and 30.3% (- to + 9.1% and + to – 21.2%) in CT/A and CT arms, respectively.
Conclusions
Baseline imbalance in sTILs and iTILs might have resulted in smaller differences of pCR between arms. Atezo increased pCR by more than 10% in “immune-rich” groups (PDL1 IC+, high sTILs/iTILs). PD-L1 dynamic is strong and divergent by arm, with atezo turning most PD-L1 neg to pos. D1c2 assessment provides an early surrogate of pCR, and high rate of tumor absence may suggests that shorter therapy may be enough for some cases.
Clinical trial identification
Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1 (NeoTRIPaPDL1) (NCT02620280).
Legal entity responsible for the study
Fondazione Michelangelo.
Funding
Associazione Italiana per la Ricerca sul Cancro (AIR) (IG 2018 ID 21787), Breast Cancer Research Foundation, Roche, Celgene.
Disclosure
G. Bianchini: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genomic Helath; Honoraria (self): Neopharm Israel; Advisory/Consultancy: Eisai; Advisory/Consultancy: Daiichi Sankyo; Honoraria (self): Chugai; Advisory/Consultancy: Sanofi. C-S. Huang: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: F. Hoffman-La Roche; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Obi; Research grant/Funding (institution): Eirgenix. D. Egle: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Travel/Accommodation/Expenses: MSD. C. Zamagni: Honoraria (self): Takeda; Honoraria (self): Pierre Fabre; Honoraria (self): Teva; Honoraria (self): Istituto Gentili; Advisory/Consultancy: Roche; Advisory/Consultancy: Eisai; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: Tesaro; Advisory/Consultancy: QuintilesIMS. M. Thill: Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Celgene; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony: MSD. E.M. Ciruelos: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. R. Greil: Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: AstaZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Sandoz; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Gilead; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: MSD. M.A. Colleoni: Honoraria (self): Novartis; Advisory/Consultancy: PierreFabre; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: OBI Pharma; Advisory/Consultancy: Celldex; Advisory/Consultancy: AstraZeneca. L. Del Mastro: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Honoraria (self): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Takeda; Honoraria (self): MSD; Honoraria (self): Genomic Health; Travel/Accommodation/Expenses: Celgene. G. Viale: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche Genentech; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Celgene. L. Gianni: Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: ADC Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy: GI Therapeutics; Advisory/Consultancy: Synthon; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Merk Sharp & Dome; Advisory/Consultancy: Genentech; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Odonate Therapeutics; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Tahio Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Zymeworks; Advisory/Consultancy: Genenta; Advisory/Consultancy: MetIS; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Revolution Medicine; Advisory/Consultancy: CD47; Advisory/Consultancy: Synaffix; Research grant/Funding (institution): Daiichi Sankyo. All other authors have declared no conflicts of interest.
162MO - Neoadjuvant chemotherapy and immunotherapy in Luminal B BC: Results of the phase II GIADA trial
- Maria Vittoria Dieci (Padova, Italy)
Abstract
Background
The role of immunotherapy in HR+/HER2- breast cancer is underexplored. The GIADA trial (EUDRACT 2016-004665-10) is a phase II study of neoadjuvant chemotherapy, nivolumab and endocrine therapy for Luminal B breast cancer patients.
Methods
Premenopausal patients with Luminal B breast cancer (HR+/HER2- and G3 or Ki67>20%) candidate to neoadjuvant chemotherapy received: 3 cycles of epirubicin/cyclophosphamide Q3W followed by 8 cycles of nivolumab 240 mg Q2W, triptorelin started concomitantly to chemotherapy and exemestane started concomitantly to nivolumab. To reject the null hypothesis, at least 8/43 pCR (ypT0/is and ypN0) had to be observed. Secondary endpoints included safety and biomarkers.
Results
43 patients were included: median age 45y, clinical stage II (81%) and IIIA (19%). All patients started treatment and underwent surgery, 42 received
Conclusions
A neoadjuvant sequence of anthracycline chemotherapy and nivolumab (+ endocrine therapy) induced a 16.3% pCR rate in Luminal B breast cancer patients (primary endpoint not met). Liver toxicity accounted for most Grade
Clinical trial identification
EUDRACT 2016-004665-10.
Legal entity responsible for the study
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy.
Funding
Bristol-Myers Squibb (financial support and drug).
Disclosure
M.V. Dieci: Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Celgene. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Roche. A. Musolino: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy: Macrogenics; Research grant/Funding (institution): AstraZeneca. S. Spazzapan: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Gentili; Advisory/Consultancy: Takeda; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Cell-dex therapeutics; Travel/Accommodation/Expenses: Tesaro; Travel/Accommodation/Expenses: Teva. P.F. Conte: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck-Serono. All other authors have declared no conflicts of interest.
163MO - Randomized phase II study of eribulin-based neoadjuvant chemotherapy for triple-negative primary breast cancer patients stratified by homologous recombination deficiency status (JBCRG-22)
- Hiroko Bando (Tsukuba, Ibaraki, Japan)
Abstract
Background
Eribulin mesylate (Eri) improves survival in patients with metastatic triple negative breast cancer (TNBC) and its toxicity profile differs from that of taxanes or anthracyclines-based regimen (A). We explored Eri-based neoadjuvant regimens for primary TNBC patients stratified by homologous recombination deficiency (HRD) and BRCA1/2 germline status in a prospective randomized phase II study.
Methods
The study enrolled patients with cT1c–T3(<=7 cm), cN0–N1, and M0, TNBC. Patients <65 years old (yo) with HRD+ or BRCA1/2 variant+ cancer were allocated to group A1 (4 cycles of weekly paclitaxel [wP] + carboplatin [Cb] then 4 of A) or A2 (4 cycles of Eri + Cb then 4 of A). Patients >=65 yo, or <65 yo with HRD- were allocated to group B1 (6 cycles of Eri + cyclophosphamide) or B2 (6 cycles of Eri + capecitabine), each with 4 cycles of A for non-responders to the first 4 cycles of Eri-based therapy. Age, tumor size, nodal status and Ki67-LI were stratification factors. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Secondary endpoints were safety, ORR and breast conservation rate (BCR).
Results
The full analysis set comprised data from all 99 patients enrolled (2/2017-1/2019). Characteristics were similar across groups. In B1 and B2, 48.1% and 55.6%, respectively, completed 6 cycles of an Eri-based regimen. The pCR rates in A1, A2, B1and B2 were 65.2%, 45.5%, 18.5% and 18.5%, respectively (Table). No major difference was seen in secondary endpoints, but peripheral neuropathy incidence was 73.9% in A1 versus 31.8%, 22.2%, 25.9% in A2, B1, B2, respectively. Patient characteristics and response * Median (range)
Group A1 A2 B1 B2 N 23 22 27 27 Age* 44.0 (28, 64) 47.5 (26, 63) 59.0 (35, 70) 60.0 (37, 70) Tumor size, mm* 23.0 (13, 60) 26.5 (13, 64) 30.0 (12, 70) 26.0 (12, 92) cN(+), n (%) 8 (34.8) 8 (36.4) 11 (40.7) 10 (37.0) Ki67, %* 58.0 (20, 92) 66.2 (36, 90) 51.6 (16, 90) 48.0 (16, 82) RDI (P / Eri), % 87.1 83.9 87.8 86.2 CpCRypN0,% (90% CI) 65.2 (46.0, 81.4) 45.5 (27.1, 64.7) 18.5 (7.6, 35.1) 18.5 (7.6, 35.1) ORR, % (95% CI) 95.7 (78.1, 99.9) 86.4 (65.1, 97.1) 59.3 (38.8, 77.6) 70.4 (49.8, 86.2) BCR, % (95% CI) 26.1 (10.2, 48.4) 54.5 (32.2, 75.6) 29.2 (12.6, 51.1) 40.0 (21.1, 61.3)
Conclusions
In TNBC patients with HRD+ or BRCA1/2 variant+ (<65 yo), pCR rate was 65% for wP+Cb followed by A and 46% for Eri+Cb followed by A. Neurotoxicity was less frequent with Eri-based regimens, which are feasible in this neoadjuvant setting. Biomarker studies are on-going.
Clinical trial identification
UMIN-CTR: UMIN000023162.
Legal entity responsible for the study
Japan Breast Cancer Research Group.
Funding
Japan Breast Cancer Research Group and Eisai Co., Ltd.
Disclosure
H. Bando: Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Kyowa Kirin; Honoraria (self), Outside the submitted work: Taiho; Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Nihon Kayaku; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Novartis. N. Masuda: Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Chugai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Pfizer; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eli Lilly; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eisai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Takeda; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Kyowa Kirin; Research grant/Funding (institution), Outside the submitted work: MSD; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Novartis; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Daiichi Sankyo; Advisory/Consultancy, Board of directors: Japan Breast Cancer Research Group Association. T. Yamanaka: Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Kyowa Kirin; Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Daiichi Sankyo. M. Takahashi: Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Pfizer. S. Nagai: Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Taiho ; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Eisai. S. Ohtani: Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Eisai. T. Aruga: Honoraria (self), Outside the submitted work: Eisai. Y. Kikawa: Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Taiho; Honoraria (self), Outside the submitted work: Chugai. H. Kasai: Research grant/Funding (institution): Eisai; Honoraria (self), Outside the submitted work: Chugai. H. Kawabata: Research grant/Funding (institution): Chugai; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Daiichi Sankyo. S. Morita: Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Bristol-Myers Squibb Company; Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: MSD; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Taiho. R. Uozumi: Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Sawai; Honoraria (self), Outside the submitted work: CAC Croit.
S. Ohno: Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eisai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Taiho; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Kyowa Kirin; Honoraria (self), Outside the submitted work: Nihon Kayaku. M. Toi: Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Chugai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Takeda; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: Kyowa Kirin; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Taiho; Research grant/Funding (institution), Outside the submitted work: JBCRG association; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: Daiichi Sankyo; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: MSD; Honoraria (self), Outside the submitted work: Genomic Health; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Konica Minolta; Research grant/Funding (institution), Outside the submitted work: Astellas; Honoraria (self), Outside the submitted work: Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Shimadzu; Honoraria (self), Outside the submitted work: Yakult; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Nihon Kayaku; Research grant/Funding (institution), Outside the submitted work: AFI Technologies; Advisory/Consultancy, Outside the submitted work: Athenex Oncology; Advisory/Consultancy, Board of directors: JBCRG association,; Advisory/Consultancy, Board of directors: Organisation for Oncology and Translational Research; Advisory/Consultancy, Board of directors: Kyoto Breast Cancer Research Network. All other authors have declared no conflicts of interest.
164MO - Impaired Ki67 response towards neoadjuvant endocrine therapy in luminal breast cancer is associated with mutations conferring endocrine resistance: WSG-ADAPT HR+/HER2- translational results
- Isabel Grote (Hannover, Germany)
Abstract
Background
Adjuvant endocrine therapy is a cornerstone in the treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC). Neoadjuvant endocrine induction therapy (EIT) suppresses tumor cell proliferation and provides a clinically applicable read-out system for endocrine responsiveness. In a proof-of-principle study, we hypothesized, that incomplete growth suppression following to EIT is associated with genetic alterations in endocrine resistance genes.
Methods
Genetic alterations in candidate endocrine resistance genes (
Results
A total of n=351/622 (56.4%) BC cases harbored genetic alterations in at least one candidate gene.
Conclusions
Our findings indicate that mutations associated with endocrine resistance and metastatic breast cancer [1], are enriched in short term endocrine treated primary luminal breast cancers with impaired Ki67 response. Ki67 response towards neoadjuvant endocrine treatment appears to reflect the genetic risk in breast cancer.
Clinical trial identification
NCT0177920.
Legal entity responsible for the study
West German Study Group.
Funding
The study was supported by a grant from the Deutsche Krebshilfe to SB, MC, and HK (Grant Number 70112954).
Disclosure
S. Kümmel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Somatex; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: PFM; Honoraria (self), Advisory/Consultancy: Medical; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sonoscape; Leadership role, Shareholder/Stockholder/Stock options: WSG; Leadership role: AGO. M. Braun: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Exact Sciences; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Medac; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Teva. R. Wuerstlein: Honoraria (self): Agendia; Honoraria (self): Amgen; Honoraria (self): Aristo; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Carl Zeiss; Honoraria (self): Celgene; Honoraria (self): Clinsol; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eisai; Honoraria (self): Genomic Health; Honoraria (self): Glaxo Smith Kline; Honoraria (self): Hexal; Honoraria (self): Lilly; Honoraria (self): Medstrom Medical; Honoraria (self): MSD; Honoraria (self): Mundipharma; Honoraria (self): Nanostring; Honoraria (self): Novartis; Honoraria (self): Odonate; Honoraria (self): Paxman; Honoraria (self): Palleos; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): PumaBiotechnology; Honoraria (self): Riemser; Honoraria (self): Roche; Honoraria (self): Sandoz/Hexal; Honoraria (self): Seattle Genetics; Honoraria (self): Tesaro Bio. All other authors have declared no conflicts of interest.
Invited Discussant LBA13, 162MO, 163MO and 164MO
- Hope S. Rugo (San Francisco, CA, United States of America)
LBA14 - De-escalated neoadjuvant T-DM1 with or without endocrine therapy (ET) vs trastuzumab+ET in early HR+/HER2+ breast cancer (BC): ADAPT-TP survival results
- Nadia Harbeck (Munich, Germany)
Abstract
Background
HR+/HER2+ BC is a distinct entity associated with different molecular and therapeutic features compared to HR-/HER2+ BC. The HER2 antibody drug conjugate T-DM1 is highly effective in metastatic and early HER2+ BC. So far, no survival data for de-escalated T-DM1-based (neo)adjuvant regimens without systemic chemotherapy (CT) are available. Here, we present first survival data from ADAPT-TP.
Methods
The prospective WSG-ADAPT-TP phase II-trial is part of the ADAPT-umbrella protocol (NCT
Results
After median follow-up of 5 years, no significant differences between study arms were observed regarding DFS (T-DM1/T-DM1+ET/T+ET 5-y rate: 88.9%, 85.3%, and 84.6%) and OS (97.2%, 96.4% and 96.3%). pCR (vs. non-pCR) after the 12-week study treatment was strongly associated with improved DFS (5y DFS 92.7% vs. 82.7, HR=0.40, 95% CI 0.18-0.85). Among 117 pts with pCR, no further CT was given in 41 pts (35%). Significant differences between CT-treated vs. non-treated pCR pts regarding baseline characteristics were only observed for age (median 50y vs. 56y, p=0.005); similar 5y DFS was observed in both groups (92.1% (95%-CI: 78-97%) vs. 93% (84-97%)). Only 3 deaths occurred in pts with pCR.
Conclusions
Early pCR after 12 weeks of therapy was strongly associated with improved outcome in ADAPT TP and may serve as a predictive marker for CT treatment (de)-escalation. Despite substantially higher pCR rates, T-DM1 +/- ET was not associated with different DFS or OS vs. T+ET, most likely due to standard CT, given to all non-pCR pts and most pCR pts or small sample size of study. Excellent 93% 5y DFS in pts with pCR after only 12 weeks of T-DM1 +/- ET (even w/o further CT) is promising and may serve as a basis for further prospective trials addressing omission of CT overtreatment in carefully selected patients with HER2+ early BC.
Clinical trial identification
Legal entity responsible for the study
West German Study Group.
Funding
Roche.
Disclosure
N. Harbeck: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Seattle Genetics. U. Nitz: Honoraria (self), Advisory/Consultancy: Amgen; AstraZeneca; Genomic Health; Novartis; Pfizer; Pierre Fabre; Roche; Zodiac Pharma. S. Kuemmel: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex Medical Technologies, Daiichi Sankyo, pfm medical, Pfizer, MSD, Lilly, SonoscapeRoche, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex Medical Technologies, Daiichi Sanky. M. Braun: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca, Celgene, Eisai, Genomic Health, GalaxoSmithKline, Medac, Novatis, Pfizer, Roche, RTI Surgical, Teva. J. Tio: Travel/Accommodation/Expenses: Roche. B. Aktas: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer, Roche Pharma, Novartis Pharma, AstraZeneca, Amgen, Tesaro Bio Germany, PharmaMar, Eisai. W. Malter: Honoraria (self), Advisory/Consultancy: Nanostring, Celgene, Roche. R. Wuerstlein: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Daiichi-Sankyo, Eisai, Genomic Health, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, NanoString, Novartis, Odonate, Paxman, Palleos, Pfizer, Pi. H. Kreipe: Honoraria (self), Advisory/Consultancy: Roche, Novartis, AstraZeneca, Genomic Health. All other authors have declared no conflicts of interest.
165MO - Patient (pt) preference for the pertuzumab-trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) in HER2-positive early breast cancer (EBC): Primary analysis of the open-label, randomised crossover PHranceSCa study
- Joyce O'Shaughnessy (Dallas, United States of America)
Abstract
Background
SC formulations of intravenous (IV) treatments (tx) are less invasive with shorter administration (admin) times; reducing pts’ clinic time, freeing up healthcare resources and potentially enabling admin outside of hospitals.
Methods
Pts completed neoadjuvant PH + chemotherapy + surgery and were randomised 1:1 to 3 cycles of PH IV followed by 3 cycles of PH FDC SC or vice-versa (crossover period). Pts then chose SC or IV to continue EBC tx up to 18 cycles (continuation period). Primary objective: to assess pt preference for PH FDC SC. Key secondary objectives: patient satisfaction, healthcare professional (HCP) perceptions on time/resource impact, and safety. ClinicalTrials.gov NCT03674112.
Results
At primary analysis, 160 pts were randomised; all pts completed crossover tx; 44% completed continuation tx at cut-off (24-02-20). 136 pts (85%; 95% CI 79–90%) preferred SC; 22 (14%) preferred IV; 2 (1%) had no preference. Main reasons for SC preference: reduced clinic time (n=119) and comfort during administration (n=73). 141 (88%) were very satisfied or satisfied with SC vs. 108 (68%) with IV. 87% chose SC to complete HER2-targeted therapy. HCPs’ perceptions on median pts’ time in the tx room across cycles 1–6 for SC vs. IV admin were 33–50 vs. 130–300 min, respectively. The rates of serious adverse events (AEs) and grade ≥3 AEs were low; the most common AEs were as expected (table). There were a higher number of injection site reactions with SC, mainly grade 1–2. AE rates before and after switching were similar (PH IV→PH FDC SC: 78%→73%; PH FDC SC→PH IV: 78%→64%), with no new safety signals.
% of pts PH IV pooled crossover n=160 PH FDC SC pooled crossover n=160 PH IV pooled continuation n=21 PH FDC SC pooled continuation n=137 All pts n=160 AE 71 75 62 51 90 Common AEs (≥5% of pts) - Radiation skin injury 17 11 0 1 28 - Injection site reaction 0 23 0 7 26 - Diarrhoea 10 8 19 10 22 - Fatigue 6 6 5 3 11 - Arthralgia 4 5 10 1 11 - Hot flush 4 6 0 2 10 - Headache 2 3 10 1 6 - Myalgia 3 2 10 0 6 - Rash 1 1 10 1 5 - Bone pain 0 0 10 0 1 AE with fatal outcome 0 0 0 0 0 Grade ≥3 AE 4 3 10 3 8 Serious AE 4 1 0 2 6 AE leading to any study tx discontinuation 0 1 5 0 1
Conclusions
PHranceSCa clearly showed that the majority of pts preferred PH FDC SC over PH IV. PH FDC SC was generally well tolerated with no new safety signals. PH FDC SC offers a quicker alternative to PH IV and reduces patients’ time in the tx room.
Clinical trial identification
NCT03674112.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
J. O'Shaughnessy: Advisory/Consultancy: AbbVie, Agendia, Amgen, AstraZeneca, BMS, Celgene, Eisai, Genentech, Inc., Immunomedics, Ipsen, Lilly, Merck, Novartis, Odonate, Pfizer, Puma, Prime Oncology, F. Hoffmann-La Roche Ltd, Seattle Genetics and Daiichi Sankyo; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. S. Sousa: Advisory/Consultancy, Travel/Accommodation/Expenses, Also congresses and lectures: F. Hoffmann-La Roche Ltd, Novartis, Pfizer, Tesaro, AstraZeneca, MSD, Pierre Fabre and Eisai; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. J. Cruz: Honoraria (self), Speaker: GSK, AstraZeneca, F. Hoffmann-La Roche Ltd, Novartis, PharmaMar, Eisai, Lilly, Celgene, Astellas, Amgen and Pfizer; Advisory/Consultancy: GSK, AstraZeneca, F. Hoffmann-La Roche Ltd, Novartis, PharmaMar, Eisai, Lilly, Celgene, Astellas, Amgen and Pfizer; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. L. Fallowfield: Honoraria (self): Pfizer, AstraZeneca, BMS, Lilly, Novartis, Genomic Health and Nanostring; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. P. Auvinen: Non-remunerated activity/ies, Third-party writing assistance. Funding for ESMO Breast Cancer Congress 2019: F. Hoffmann-La Roche Ltd. C. Pulido: Speaker Bureau/Expert testimony, Public speaking: AstraZeneca, Grunenthal and Novartis; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd; Non-remunerated activity/ies, Writing engagements: AstraZeneca. A. Cvetanovic: Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. S. Wilks: Advisory/Consultancy: Seattle Genetics; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. L. Ribeiro: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche Pharmaceuticals, Merck Serono, MSD, BMS, AstraZeneca and Pfizer; Non-remunerated activity/ies, Personal medical education and participation in congresses: BMS, Roche Pharmaceuticals, Merck Serono, Pfizer, Amgen and Pierre Fabre; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. M. Burotto: Advisory/Consultancy, Speaker Bureau/Expert testimony, Speaking at industry symposiums: F. Hoffmann-La Roche Ltd, MSD, BMS, AstraZeneca and Novartis; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. D. Klingbiel: Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. D. Messeri: Full/Part-time employment, Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. A. Alexandrou: Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd; Full/Part-time employment: Roche Products Limited. P. Trask: Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd; Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech, Inc.. J. Fredriksson: Full/Part-time employment, Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. Z. Machackova: Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. L. Stamatovic: Honoraria (self), Speaker: AstraZeneca, Novartis, Pfizer and F. Hoffmann-La Roche Ltd; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd.
166MO - A phase III trial to compare the efficacy, safety, pharmacokinetics and immunogenicity of HD201 to trastuzumab in HER2+ early breast cancer patients (TROIKA)
- Pivot Xavier (Strasbourg, France)
Abstract
Background
HD201, developed by Prestige Biopharma Ltd is a biosimilar candidate to Herceptin. TROIKA is a randomised, double-blind, parallel-group, equivalence, multicentre Phase III study designed to compare the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HD201 to Herceptin in patients with HER2 positive early breast cancer (EBC).
Methods
503 patients with HER2+ EBC were randomised in a 1:1 ratio to receive either HD201 or Herceptin in neoadjuvant settings for 8 cycles in combination with chemotherapy (4 cycles of docetaxel followed by 4 cycles of epirubicin/cyclophosphamide). The patients then underwent surgery followed by 10 cycles of HD201 or Herceptin monotherapy. The primary objective was to demonstrated equivalence in total pathologic complete response (tpCR) rate between treatments. The pre-specified equivalence margins were +/- 15% for the 95% confidence interval of the absolute difference for tpCR rates. Secondary endpoints including breast pathologic complete response (bpCR), overall response rate (ORR), event-free survival (EFS), PK, immunogenicity, and safety were assessed.
Results
The tpCR rates were 46.60% and 46.20% for HD201 and Herceptin respectively. The difference of tpCR rate was 0.50% and the 95% CI was -8.6% - 9.6%, both contained within the pre-defined equivalence margins. Secondary endpoints were similar between HD201 and Herceptin. The bpCR rate of 55.00% and 53.40% and the ORR of 90.80% and 89.40% for HD201 and Herceptin respectively. Safety was comparable between HD201 and Herceptin during neoadjuvant period. PK equivalence was demonstrated with mean steady-state Ctrough levels of 53.72 ug/mL in the HD201 group and 51.64 ug/mL in the Herceptin group at the onset of Cycle 8, providing a 4.0% [-2.6%; 10.6%] on the mean relative difference between the two treatments within the pre-specified interval [-20%;+20%]. Interim data indicate comparable immunogenicity between HD201 and Herceptin.
Conclusions
Equivalence in efficacy, safety, PK and immunogenicity profiles was demonstrated between HD201 and Herceptin. TROIKA is currently in its follow up phase. Complete safety, immunogenicity and survival data are to follow.
Clinical trial identification
Eudract: 2016-004019-11.
Legal entity responsible for the study
Prestige Biopharma Ltd.
Funding
Prestige Biopharma Ltd.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant LBA14, 165MO and 166MO
- Prudence Francis (Melbourne, VIC, Australia)
167MO - Longitudinal evaluation of serum assessed non-adherence to tamoxifen (TAM) among premenopausal patients (pts) in the prospective multicenter CANTO cohort
- Barbara Pistilli (Villejuif, France)
Abstract
Background
Using TAM serum assessment, we demonstrated that 1 in 6 premenopausal pts with early breast cancer (EBC) are non-adherent to TAM at 1 year (Y1) from treatment initiation. Most of them did not overtly declare non-adherence. We now evaluate the longitudinal evolution of non-adherence to TAM by using serum assessment and pts’ self-declarations at year 3 (Y3).
Methods
CANTO COMPLETE, a sub-study of CANTO cohort (
Results
718 pts were evaluable at Y3. Median age 46 (IQR 42–49), partnered 536 (78.7%), post-graduation education 362 (52.6%), stage I BC 333 (46.4%) and received chemotherapy 444 (61.8%). At Y3, serum assessment showed that 260 (36.2%) pts were non-adherent, of whom 226 (31.5%) with TAM <LLOQ. By matching with pts’ declarations: 118 out of 260 (45.4%) did not report non-adherence. The table below reports the longitudinal evolution of biochemical adherence. Regression model showed that younger age (adjusted (a) OR for 1 year increase in age= 0.94 [95% CI 0.91-0.98]) and hot flashes at Y1 (aOR = 1.62 [1.03-2.54]) were associated to biochemical non-adherence. *85 missing at Y1
Definition TAM at Y1 (ng/mL) TAM at Y3 (ng/mL) N pts (%) * <60 <60 83 (13.1) ≥60 <60 144 (22.8) <60 ≥60 14 (2.2) ≥60 ≥60 392 (61.9)
Conclusions
At Y3 from initiation of TAM, more than 1 patient out of 3 was poorly adherent to adjuvant TAM, showing that non-adherence sharply increased from Y1 to Y3. Serum assessment was able to identify a higher proportion of pts who have dropped out from treatment early.
Clinical trial identification
NCT01993498.
Legal entity responsible for the study
UNICANCER.
Funding
Institut National Cancer-France grant (SHS-E-SP 18-129) to Barbara Pistilli, a Career Catalyst Research grant from Susan G. Komen (CCR17483507) to Ines Vaz-Luis, a Fondation ARC pour la recherche sur le cancer grant (CANTO-WORK-programme labillisé) to Ines Vaz-Luis and Gwenn Menvielle and the Philanthropic Odyssea Gustave Roussy Program. The CANTO study is supported by the French Government under the “Investment for the Future” program managed by the National Research Agency (ANR), grant n° ANR-10-COHO-0004.
Disclosure
B. Pistilli: Honoraria (institution), Advisory/Consultancy: Puma Biotechnology; Speaker Bureau/Expert testimony: Pierre Fabre; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony: Myriad Genetics; Travel/Accommodation/Expenses: MSD Oncology; Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Merus. A.R. Ferreira: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. A. Bardet: Advisory/Consultancy: Roche SAS. P.H. Cottu: Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self): Lilly; Honoraria (institution): Novartis. S. Michiels: Advisory/Consultancy: IDDI; Advisory/Consultancy: Janssen Cilag; Speaker Bureau/Expert testimony: Hexal; Speaker Bureau/Expert testimony: Steba; Speaker Bureau/Expert testimony: IQVIA; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Sensorion; Speaker Bureau/Expert testimony: Biophytis; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Yuhan. I. Vaz Luis: Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Kephren. All other authors have declared no conflicts of interest.
168MO - GeparX: Denosumab (Dmab) as add-on to different regimen of nab-paclitaxel (nP)-anthracycline based neoadjuvant chemotherapy (NACT) in early breast cancer (BC): Subgroup analyses by RANK expression and HR status
- Theresa Link (Dresden, Germany)
Abstract
Background
In the GeparX trial, the addition of Dmab to NACT did not increase the pCR rate in early BC (41% vs. 43%; p=0.58) but nP q1 weekly (w) resulted in a significantly higher pCR rate than given d1, 8 q22 (45% vs. 39%; p=0.06; Blohmer et al. SABCS 2019). Here, we evaluated the pCR rates in different subgroups and in relation to RANK expression.
Methods
780 patients (pts) with high risk early BC were randomized 2x2 first to +/- Dmab (120mg sc q4w/6 cycles) and then to two different nP regimen (nP 125mg/m2 q1w or d1, 8 q22) followed by EC (q2w or q3w) stratified by subtype, sTILs and EC regimen. Carboplatin was given in triple-negative (TNBC) and anti-HER2-therapy in HER2+ BC. RANK was stained on pre-therapeutic core biopsies (n=667) with the antibody RANK/Envision System HRP (DAB) and was analyzed immunohistochemically for percentage of membranous tumor cell staining (RANK high if >5 %).
Results
RANK expression was high in 20.8% of biopsies. It correlated with younger age (< 40 yrs: 15.5% low vs. 32.4% high; p<0.001), HR-status (ER and PR negative: 40.7% low vs. 69.1% high; p<0.001), tumor grade (G3: 63.6% low vs. 74.8 % high; p=0.03), Ki67 (>20%: 80.7% low vs. 91.4 % high; p=0.002) and stromal (s) TILs (>50% sTILs: 7.4% low vs. 10.8% high; p=0.002). High RANK expression resulted in a significantly higher pCR rate than RANK low (49.6% vs. 39.4%; p=0.037). But this was not associated with Dmab effect (RANK high: OR with vs. without Dmab 0.864 [90% CI 0.494-1.51], p=0.67; RANK low: OR 1.10 [90% CI 0.821-1.48], p=0.59; p interaction=0.53). pCR rates (ypT0 ypN0) are shown in the table.
Subgroup p-value (stratified test) TNBC 55.5 49.4 0.422 HER2+ BC 56.6 52.6 0.940 Luminal BC 21.6 22.3 0.961 TNBC 52.5 58.0 0.313 HER2+ BC 55.8 53.9 0.821 EC q2w 40.3 43.3 0.609 EC q3w 41.8 42.3 0.794 >50% sTILs 71.0 61.3 0.528 ≤50% sTILs 38.4 41.2 0.453 Luminal BC 22.6 21.3 0.913 HER2+ BC 57.9 51.9 0.289 EC q3w 42.6 41.5 0.597 >50% sTILs 71.0 61.3 0.135 ≤50% sTILs 42.6 37.0 0.126 Without Dmab 41.5 44.1 0.665
Conclusions
A high RANK expression was associated with significantly higher pCR rates (49.6% vs. 39.4%; p=0.037). This effect was pronounced in pts with luminal BC. However, a clinical benefit of Dmab in relation to RANK expression could not be shown. Further explorative analyses are still ongoing.
Clinical trial identification
NCT02682693.
Legal entity responsible for the study
German Breast Group.
Funding
The trial was financially supported by Amgen and Celgene including drug supply.
Disclosure
T. Link: Non-remunerated activity/ies: PharmaMar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self), Non-remunerated ctivity/ies: MSD; Honoraria (self): Amgen; Honoraria (self), Non-remunerated activity/ies: Pfizer; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Celgene; Honoraria (self), Non-remunerated activity/ies: Clovis. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): SonoScape. M. Untch: Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: AbbVie; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Amgen GmbH ; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: AstraZeneca; Honoraria (institution), All fees to the institution/employer: BMS; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Celgene GmbH ; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Daiichi Sankyo ; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Eisai GmbH ; Honoraria (institution), All fees to the institution/employer: Lilly Deutschland; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Lilly Int.; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: MSD Merck; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Mundipharma; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Myriad Genetics ; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Pfizer GmbH; Honoraria (self): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Novartis ; Honoraria (institution), All fees to the institution/employer: Pierre Fabre; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Clovis Oncology. P.A. Fasching: Speaker Bureau/Expert testimony, Lectures: Amgen; Advisory/Consultancy, Advisory Board: Roche; Research grant/Funding (institution): BionTech; Honoraria (self), Advisory/Consultancy, Advisory Board: Roche; Advisory/Consultancy, Advisory Board: Pfizer; Advisory/Consultancy, Advisory Board: Celgene; Speaker Bureau/Expert testimony, Lectures: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory Board, Lectures: Merck Sharp & Dohme; Advisory/Consultancy, Advisory Board: Macrogenics; Advisory/Consultancy, Advisory Board: Eisai; Advisory/Consultancy, Advisory Board: Puma; Research grant/Funding (institution), Research Support: Cepheid; Honoraria (self), Advisory Board; Lectures: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Research Support; Advisory Board: Novartis; Advisory/Consultancy, Advisory Board: AstraZeneca; Speaker Bureau/Expert testimony, Lectures: Amgen. A. Schneeweiss: Research grant/Funding (institution), Research Grant: Celgene; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: AbbVie; Research grant/Funding (institution), Research Grant: Molecular Partner; Speaker Bureau/Expert testimony, Expert testimony: Roche; Speaker Bureau/Expert testimony, Expert testimony: AstraZeneca; Travel/Accommodation/Expenses, Travel expenses: Celgene; Travel/Accommodation/Expenses, Travel expenses: Roche; Honoraria (self), Honoraria: Roche; Honoraria (self), Honoraria: Celgene; Honoraria (self), Honoraria: Pfizer; Honoraria (self), Honoraria: AstraZeneca; Honoraria (self), Honoraria: Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Travel/Accommodation/Expenses, Travel Expenses: Pfizer; Research grant/Funding (self), Medical writing grant: Roche. P. Wimberger: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): PharmaMar; Honoraria (self): Eisai; Honoraria (self): Teva; Honoraria (self): Clovis; Honoraria (self): Tesaro. S. Seiler: Research grant/Funding (institution), GeparOla study was supported by AstraZeneca: AstraZeneca; Advisory/Consultancy, Advisory Boards: Amgen; Advisory/Consultancy, Advisory Boards: Hexal; Speaker Bureau/Expert testimony, Presentations: Roche; Honoraria (self), Advisory Boards: Mundipharma; Travel/Accommodation/Expenses, Travel costs: Novartis. J. Huober: Honoraria (self), Travel/Accommodation/Expenses, Travel expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses, Travel expenses: Roche; Honoraria (self): Lilly; Honoraria (self): Celgene; Honoraria (self), Travel/Accommodation/Expenses, Travel expenses: AstraZeneca; Honoraria (self): MSD; Honoraria (self): AbbVie; Honoraria (self): Eisai; Research grant/Funding (institution): Hexal; Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Novartis; Travel/Accommodation/Expenses, Travel expenses: Daiichi. W.D. Schmitt: Research grant/Funding (institution): German Breast Group; Honoraria (self): AstraZeneca. C. Jackisch: Honoraria (self): AstraZeneca; Honoraria (self): Roche. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Pfizer. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Celgene. C. Denkert: Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Research grant/Funding (institution): Myriad Genetics; Shareholder/Stockholder/Stock options, Cofounder and shareholder: Sividon Diagnostics / Myriad; Licensing/Royalties, cancer immunotherapy: EP18209672; Licensing/Royalties, therapy response: EP20150702464; Licensing/Royalties, Ki67 evaluator: Software (VMscope digital pathology). S. Loibl: Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Amgen; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Celgene; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Novartis; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Roche; Honoraria (institution), honorario for lectures and ad boards paid to institute: Seattle Genetics; Honoraria (self), honorario for lectures and ad boards paid to institute: PriME/ Medscape; Speaker Bureau/Expert testimony, lecture: Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Research grant/Funding (institution), honorarioumpaid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), honorarium for ad boards paid to institute: Samsung; Advisory/Consultancy, Advisor paid to institute: Eirgenix; Advisory/Consultancy, advisor honorarium paid to institute: BMS; Advisory/Consultancy, advisor honorarium paid to institute: Puma; Honoraria (institution), honorarium paid to insitute: MSD; Research grant/Funding (institution), paid to institue: Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. All other authors have declared no conflicts of interest.
169MO - Development and validation of a magnetic resonance imaging radiomics-based signature to predict axillary lymph node metastasis and disease-free survival in patients with breast cancer: A multicenter cohort study
- Herui Yao (Guangzhou, China)
Abstract
Background
Preoperative non-invasive tools to accurately predict the axillary lymph node (ALN) status and disease-free survival (DFS) in early breast cancer are lacking. Therefore, we have developed and validated contrast–enhanced multiparametric magnetic resonance imaging (MRI) radiomic-based signatures for preoperative identification of ALN metastasis and assessment of individual disease-free survival (DFS) in early breast cancer.
Methods
In this multicentre, retrospective, cohort study, we included early stage breast cancer patients from four hospitals in China, which were divided randomly (7:3) into the development and validation cohorts. Radiomic features were extracted from preoperative MR imaging. LASSO and random forest algorithm were applied to select key radiomic features from the development cohort. Two nomograms incorporating radiomic and clinical signatures were developed to predict ALN status and individual DFS, respectively, based on multivariable logistic or radiomics signature penalized Cox regression models.
Results
218,729 MRI images from 1,214 individuals were included. The ALN radiomic nomogram accurately predicted ALN metastasis in the development cohort (Area Under Curve, [AUC] = 0.92), validation cohort (AUC = 0.90), and entire cohort (AUC = 0.91). The DFS radiomic nomogram could discriminate high- from low risk patients in the development, validation, and entire cohort (HR for all 0.04,
Conclusions
This study used the largest database to date to describe the application of MRI-based artificial intelligence in patients with breast cancer, presenting novel individualized clinical-decision radiomic nomograms that could precisely predict ALN metastasis and DFS.
Clinical trial identification
NCT04003558; ChiCTR1900024020.
Legal entity responsible for the study
HRY.
Funding
National Major Science and Technology Project of China, Medical artificial intelligence project of Sun Yat-Sen Memorial Hospital, National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Guangzhou Science and Technology Major Program, Sun Yat-Sen University Clinical Research 5010 Program, Sun Yat-Sen Clinical Research Cultivating Program, Guangdong Science and Technology Department, Tencent Charity Foundation.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 167MO, 168MO and 169MO
- Shaheenah Dawood (Dubai, United Arab Emirates)