Background

As further de-escalation of axillary surgery is ongoing, new biomarkers that convey the same prognostic information as sentinel node status are called for.

Methods

To predict sentinel node status, we trained a deep learning (DL) image analysis model on H&E-stained whole slide images (WSIs) of primary tumors. For training, we used cases from the INSEMA standard arm (n=762, ca. 94 % HR+/HER2-, 3.5 % G3, less than 1% pT3/4, 13 % SLN-positive) and a cohort from the Women’s Clinic in Mannheim, Germany (n=150, all HR+/HER2-, G2, pT1/2, ca. 16 % SLN positive). We also fitted a logistic regression with clinical data (pT stage, Ki-67) for this task. Models were tested on a holdout INSEMA set (n=381), and the image model also on the higher risk TCGA BRCA cohort (n=650, ca. 72% HR+, ca. 55% SLN+). Vice versa, we trained a model on TCGA WSIs and tested it on the other cohorts.

Results

During training, the image and the clinical model yielded Areas under the Receiver Operating Characteristic Curve (AUROCs) of 0.62 and of 0.77 on the Mannheim WSIs, respectively. However, performance of the image model was random on the INSEMA (determined by blinded assessment) and TCGA BRCA test sets. The clinical classifier retained an AUROC of 0.62 on the INSEMA set. Inclusion of the image classifier output in the logistic regression did not improve performance on INSEMA. The image model trained on TCGA also yielded random performance on the INSEMA and Mannheim cohorts.

Conclusions

Image analysis algorithms trained on H&E stains of the primary tumors from INSEMA or TCGA using established techniques were unable to predict sentinel status, which may suggest a lack of systematic histological differences by lymph node status in these cohorts. Thus, DL-based WSI analysis may not be a good strategy to replace sentinel node assessment, especially in low- to intermediate-risk, hormone receptor-positive breast cancer.

Clinical trial identification

NCT02466737.

Legal entity responsible for the study

The authors.

Funding

TB, MS and EKH were funded by the TPI grant to TJB by the German Federal Ministry of Health. INSEMA trial is supported by German Cancer Aid (Deutsche Krebshilfe, Bonn, Germany), Grant No. 110580 and Grant No. 70110580 to University Medicine Rostock.

Disclosure

F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Roche, AstraZeneca, Novartis, Roche, Eisai, Gilead/Immunomedics, MSD, German Breast Group, AGO Research GmbH, Vaccibody, GSK; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Roche, Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca, VmScope digital pathology software; Financial Interests, Institutional, Research Grant: Roche, Myriad, German Breast Group. V. Nekljudova: Financial Interests, Institutional, Full or part-time Employment: GBG; Financial Interests, Institutional, Research Grant: AbbVie, AstraZeneca, BMS, Daichi-Sankyo,Gilead, Novartis, Pfizer, Roche; Non-Financial Interests, Institutional, Writing Engagements: Daiichi Sankyo, Gilead, Novartzis, Pfizer, Roche, Seagen; Other, Institutional, Other, EP14153692.0: Patent; Other, Institutional, Other, EP21152186.9: Patent; Other, Institutional, Other, EP15702464.7: Patent; Other, Institutional, Other, EP19808852.8: Patent; Other, Institutional, Royalties: VM Scope GmbH. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, AbbVie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen; Financial Interests, Institutional, Advisory Board: DSI, Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. All other authors have declared no conflicts of interest.

Background

Trastuzumab (T) and chemotherapy (CT) is a standard treatment in patients (pts) with HER2-positive (+) advanced breast cancer (ABC) at later lines of therapy. Lapatinib (L) and T have proven to be active in the same setting. The present study evaluated the efficacy, toxicity and quality of life (QoL) of T+L versus T + physician’s choice CT in pts with HER2+ ABC pretreated with at least two lines of anti-HER2 treatment.

Methods

In this open-label, multicenter, phase II trial, pts were randomly assigned 1:1 to receive either T+L with endocrine therapy at the physician’s discretion in case of hormone receptor positive ABC (arm A) or T+CT (arm B). The primary endpoint was the clinical benefit rate (CBR) and the secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life (QoL), and safety.

Results

Between 2015 and 2020, 59 pts were randomized and evaluated for the present analyses. After a median (m) follow-up of 57.5 months (mo), the CBR was 20.7% (95% CI 9.4-39.3) vs 26.7% (95% CI 13.1-44.9; P= 0.76), the mOS was 29.9 mo (95% CI 19.6-NE) vs 31.1 mo (95% CI 26.1-NE; hazard ratio [HR] 1.07, 95% CI 0.57-2.0; P=0.82) and mPFS was 3.6 mo (95% CI 3.0-5.3) vs 6.1 mo (95% CI 4.0-14.3; HR 0.63, 95% CI 0.37-1.37; P=0.08) in arm A vs arm B, respectively. Any grade (G) adverse events (AEs) occurred in 86.2% and 66.7% of pts in arm A and B, respectively. The incidence of G3-4 AEs was 24.1% and 13.3% in arm A and B, respectively. The impact on QoL significantly favored arm A (P=0.03). Table: 209P

Conclusions

No difference in efficacy was observed between T+L and T+CT. QoL deterioration was less frequent in pts in T+L arm though a higher number of any AEs was observed in these patients compared with those who received T+CT. Overall, the chemotherapy-free combination of T+L may be a valid therapeutic option for pretreated pts with HER2+ ABC.

Clinical trial identification

EudraCT 2013-005044-29; Date when the record was first entered in the EudraCT database: 16-05-2014.

Legal entity responsible for the study

Oncotech.

Funding

Novartis, GSK.

Disclosure

C. De Angelis: Financial Interests, Personal, Advisory Board, Consultant fees, travel expenses: Roche, AstraZeneca, GSK; Financial Interests, Personal, Advisory Board, consultant fees, travel expenses: Lilly; Financial Interests, Personal and Institutional, Advisory Board, Honoraria, research funding, travel expenses: Novartis; Financial Interests, Personal, Advisory Board, Honoraria, travel expenses: Pfizer; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Personal, Other, Travel expenses: Celgene. M. Pagliuca: Other, Personal, Other, Travel expenses: Gilead, Pfizer. T. Gamucci: Financial Interests, Personal, Advisory Board: Seagen, Pfizer, Eisai, Daiichi Sankyo, AstraZeneca, Novartis. M. Mansutti: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Gentili, Gilead, Novartis, Pfizer, Seagen, Roche. Z. Ballatore: Financial Interests, Personal, Other, Honoraria: Ipsen, Novartis, Roche. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Roche, Novartis, Eli Lilly, Pierre Fabre, AstraZeneca, MSD, Seagen, Gilead, Daiichi Sankyo, Pfizer, Exact Science, Ipsen, Takeda, Sanofi Genzyme. R. Bordonaro: Financial Interests, Personal, Speaker’s Bureau, Honoraria, consulting or advisory role: Novartis, AstraZeneca, Sanofi, Amgen, Roche, Pfizer, Janssen-Cilag, BMS; Financial Interests, Personal, Speaker’s Bureau, Consulting or advisory role: Bayer. S. Cinieri: Financial Interests, Personal, Other: Lilly Oncology, Seagen, AstraZeneca. A. Fabi: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Eli Lilly, Novartis, Eisai, AstraZeneca, Exact Science, Epihonpharma, Daiichi Sankyo, Gilead, Seagen. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli lilly; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. F. Puglisi: Financial Interests, Personal, Other, Honoraria: Amgen, Daiichi Sankyo, Celgene, Lilly, Gilead, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer, Seagen, Takeda, Viatris; Financial Interests, Personal, Other, Honoraria, research funding: AstraZeneca, Eisai, Roche. S. de Placido: Financial Interests, Personal, Advisory Role: Novartis, Roche, Celgene, AstraZeneca, Amgen, Eisai, Lilly, Pfizer, Gentili. M. Giuliano: Financial Interests, Institutional, Funding: Novartis, AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Exact Sciences, Lilly, MSD, Novartis, Seagen; Financial Interests, Personal, Advisory Board, Travel expenses: Pfizer, Roche; Financial Interests, Personal, Other, Travel expenses: Celgene. G. Arpino: Financial Interests, Personal, Advisory Board, Travel expenses: Roche, Pfizer, Lilly, MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Funding: Roche, Pfizer, Lilly, AstraZeneca, Novartis, MSD. All other authors have declared no conflicts of interest.

Background

Circulating tumor DNA (ctDNA) is promising as tumor-specific marker for progression surveillance in metastatic cancer. Our aim was to investigate the diagnostic power of ctDNA level for disease progression in metastatic breast cancer and to propose rationally selected ctDNA level thresholds with clinical validity.

Methods

This prospective single-center observational study conducted from July 1, 2019 to December 1, 2021, recruited 136 subjects with metastatic breast cancer for sequencing of their primary tumor in search of PIKC3A variants amenable for monitoring by droplet digital PCR. This interim analysis reports on 265 on-treatment samples from 19 subjects with PIK3CA variants H1047R or E545K. Subjects were sampled every 3-5 weeks with median follow-up of 85 (13-125) weeks and median of 14 (2-29) ctDNA time points per subject. The primary outcome was progression free survival. ROC analysis and logistic regression was performed to investigate the diagnostic power of quantitative ctDNA analysis and CA15-3 to predict progression within 12 weeks from each sampling time point. Likelihood ratios were used for rational selection of ctDNA result intervals.

Results

ctDNA level (AUC: 0.856; 95% CI 0.807-0.897)) outperformed CA15-3 (AUC: 0.737; 95% CI 0.663-0.801, P<0.001) to predict progression within 12 weeks. ctDNA level below 10 mutant copies/mL were reassuring while levels above 100 copies/mL predicted 64% of progressions earlier with median (IQR) lead time of 10 (8-20) weeks versus standard of care. Logistic regression analysis indicated complementary value of ctDNA level and the presence of two consecutive rises of CA15-3, resulting in a derived risk score with AUC of 0.908 (95% CI 0.854-0.947). A risk score < 0.15 and > 0.25 achieved 93% (95%CI 87%-96%) and 82% (95% CI 71%-90%) negative and positive predictive values respectively, resulting in a clinically informative result in 89% of blood draws.

Conclusions

Intensive quantitative ctDNA monitoring shows clinical validity for improved surveillance of disease progression in metastatic breast cancer and has potential for risk-informed scheduling of standard clinical care.

Clinical trial identification

Clinical Trial Number: B117201939334, AZ Delta General Hospital

Legal entity responsible for the study

The authors.

Funding

AstraZeneca (investigator-initiated grant, ESR-18-13805, PrecisionTrack: DNA sequencing of breast cancers for precision therapy and molecular monitoring.

Disclosure

All authors have declared no conflicts of interest.

Background

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are usually combined with fulvestrant or aromatase inhibitors for the treatment of patients with metastatic breast cancer (mBC). Drug-drug interactions may affect absorption by different mechanims, for instance, modification of digestive pH. Proton pump inhibitors (PPIs) are known to reduce the oral bioavailability of some anticancer drugs. Palbociclib is a weak base with pH-dependent solubility, therefore variations in gastric pH could affect its absorption. The objective of this study was to evaluate the interaction between PPIs and palbociclib by analizing progression-free survival (PFS) in patients with mBC.

Methods

This is a retrospective study approved by the local Ethics Committee. Patients had received palbociclib between January 2016 and December 2021. The following variables were collected: age, menopausal status, performance status, hormonal treatment (fulvestrant or aromatase inhibitors), visceral or non-visceral disease, first-line vs second-line treatment, ki67, and concomitant use of PPIs. PFS was defined as the time from starting treatment to progression of the disease. Survival was estimated with the Kaplan-Meier method, whereas Cox Regression models were used to estimate hazard ratios and the chi-square test for categorical variables.

Results

A total of 169 patients were enrolled in the study: 80 received a PPI and 86 did not, without significant differences in clinical characteristics in both groups. The median PFS was 17.3 months (95% CI: 13.83-20.76), 36 months in first-line and 13 months in second and subsequent lines. Patients taking PPIs had a shorter median PFS (14.30 versus 42.6 months, p<0.001; HR 4.18: 95% CI 2.57-6.80; p<0.0001). Median PFS was 44 vs. 14 months in first-line ans 17 vs 9 months in second or subsequent lines. The line of treatment (first vs second or beyond) and ki67 had a significant influence on DFS, whereas the remaining clinical variables did not.

Conclusions

Patients with mBC treated with hormonal therapy plus palbociclib had poor PFS when receving a concomitant PPI. Although further studies are needed in the field, caution is recommended with the long-term use of PPIs in this population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J. Álvarez Criado: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly. All other authors have declared no conflicts of interest.

Background

Clinical trials are exploring the possibility of active surveillance for low-risk ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH). However, interobserver variability in grading DCIS exists. We aim to train and evaluate a deep learning model (Deep DCIS) on breast biopsy with ADH/DCIS to improve the risk stratification of these precursor lesions.

Methods

Patients diagnosed with ADH or DCIS by breast biopsy and who received wide excision within six months were included (n=592 and 112 for primary and independent validation cohorts). Two pathologists independently evaluated nuclear grade, comedonecrosis, and focus suspicious for microinvasion and annotated patch-level labels by consensus. Estrogen receptor immunostain and apocrine features were also assessed. Clinical features (e.g., biopsy method, lesion size, BIRADS classification of ultrasound and mammogram) were collected. The model adopted Inception-V3 with a train-valid-test split and Adam optimization. The outputs of Deep DCIS comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. These parameters were combined with clinical information and hormone status to predict upstaging to invasive breast carcinoma.

Results

Deep Grade strongly correlated with the pathologists' grading on both slide- and patient-level labels. All five parameters from Deep DCIS were associated with upstaging to invasive carcinoma. Deep DCIS successfully predicted upstaging with an area under the curve (AUC) of 0.81 and an accuracy (acc) of 0.75, outperforming pathologists' evaluation (AUC 0.71 and 0.69; acc 0.67 and 0.65 from two pathologists). The prediction improved after combining Deep DCIS with clinical factors and hormone status (AUC 0.87; acc 0.79). This combined model retained its predictive power in the subgroup of ADH and low-/intermediate-grade DCIS (AUC 0.81; acc 0.76). The independent validation cohort confirmed the model's performance (AUC 0.82; acc 0.72).

Conclusions

The deep learning model refines histological evaluation of ADH and DCIS on breast biopsy and improves prediction of upstaging to invasive carcinoma on wide excision, which may help guide treatment planning in future clinical studies.

Legal entity responsible for the study

Chung-yen Huang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Vasomotor symptoms (VMS) are common side-effects experienced by women receiving adjuvant endocrine therapy for hormone receptor-positive (HR+) breast cancer that can have a substantial impact on quality of life and may lead to the discontinuation of therapy. Hormone therapy is contraindicated in women with HR+ breast cancer, and there is an unmet need for well-tolerated and effective nonhormonal treatments to safely address these symptoms. Elinzanetant is a selective neurokinin-1,3 receptor antagonist currently being evaluated for the treatment of VMS associated with menopause in the phase III OASIS program.

Trial design

OASIS 4 (NCT05587296) is an ongoing, multicentre, multicountry, double-blind, randomized, placebo-controlled, phase III study evaluating the efficacy and safety of elinzanetant 120 mg in women aged 18–70 years at high risk of developing or with a personal history of HR+ breast cancer receiving tamoxifen or aromatase inhibitors. Participants recording at least 35 moderate or severe VMS over 7 days are suitable for inclusion. Following a 6-week screening period, approximately 405 participants will be randomised at a 2:1 ratio to receive either once-daily elinzanetant 120 mg for 52 weeks or a matching placebo for 12 weeks followed by elinzanetant 120 mg for 40 weeks. After treatment, participants will undergo a 4-week follow up. Primary endpoints are the mean change in moderate or severe VMS frequency from baseline to weeks 4 and 12. Key secondary endpoints are mean change in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) 8b and Menopause-Specific Quality-of-Life (MENQOL) questionnaire from baseline to week 12. Other secondary endpoints are mean change in moderate or severe VMS severity from baseline to weeks 4 and 12 and moderate or severe VMS frequency from baseline to week 1 and over time. Primary and key secondary endpoints will be analysed using a mixed model with repeated measures. Safety will be primarily assessed using adverse event reporting throughout the duration of the study.

Clinical trial identification

NCT05587296.

Editorial acknowledgement

Medical writing assistance was provided by Emma Case, Highfield, Oxford, UK with sponsorship from Bayer.

Legal entity responsible for the study

Bayer.

Funding

Bayer AG.

Disclosure

F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Personal, Advisory Board: Gilead, IQVIA, Touchime; Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GlaxoSmithKline, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth, Gilead; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO, ESO, EORTC, BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, ASPIC. L. Zuurman, C. Caetano: Other, Institutional, Full or part-time Employment: Bayer CC AG. C. Seitz, S. Parke: Other, Institutional, Full or part-time Employment: Bayer AG. K. Laapas: Other, Institutional, Full or part-time Employment: Bayer Oy. All other authors have declared no conflicts of interest.

Background

In the phase II PHranceSCa study (NCT03674112), 85% of patients preferred the fixed-dose combination of pertuzumab (P) and trastuzumab (H) for subcutaneous injection (PH FDC SC) over PH infused intravenously (IV) as adjuvant treatment for HER2-positive early breast cancer, with no new safety signals with PH FDC SC. We present efficacy and safety data after continuation of treatment and follow-up.

Methods

Patients with locally advanced, inflammatory, or early breast cancer who had completed neoadjuvant PH + chemotherapy and surgery were randomised 1:1 to 3 cycles of PH FDC SC (600 mg P/600 mg H in 10 mL) followed by 3 cycles of PH IV (P 420 mg; H 6 mg/kg) or 3 cycles of PH IV followed by 3 cycles of PH FDC SC. If needed, loading doses were P 1200 mg /H 600 mg in 15 mL for PH FDC SC and P 840 mg/H 8 mg/kg for PH IV. After the crossover period, patients continued treatment by their preferred method (continuation period, up to 18 cycles total). Efficacy (invasive disease-free survival [IDFS]) and overall survival (OS), safety and quality of life (EORTC QLQ-C30) were assessed after 3 years.

Results

159/160 patients were treated in the continuation period (138 PH FDC SC, 21 PH IV, median 8 cycles for both) and 148 completed follow-up. The table shows safety in the continuation period. Most adverse events (AEs), including all cardiac AEs (n = 2) and anaphylaxis/hypersensitivity (n = 2), were grades 1/2. No grade 4/5 AEs occurred. There were six IDFS events (3.8%: 3-year IDFS 97.4%, 95% confidence interval [CI] = 94.9, 99.9) and two deaths (1.3%: 3-year OS 98.7%, 95% CI = 96.9, 100.0). Mean changes from baseline in EORTC QLQ-C30 were generally minimal.

Conclusions

PH FDC SC was well tolerated, with safety consistent with that of PH IV (except injection-site reactions) and no grade ≥3 anaphylaxis/hypersensitivity or new safety signals in the continuation period. Efficacy data are immature but show high IDFS and OS rates at 3 years.

For the latest information on IDFS data, please consult the Poster.

Table: 97P

Clinical trial identification

NCT03674112.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by John Carron, 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: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi. S.P. Sousa: Financial Interests, Invited Speaker: Roche, Novartis, Pfizer, MSD Oncology, AstraZeneca, Merck, GSK, Gillead. J. Cruz Jurado: Financial Interests, Personal, Advisory Board: PharmaMar, Roche, Lilly, Pfyzer, Novartis, Gilead, AstraZeneca, Daiichi, Seagen, GSK, Bayer; Financial Interests, Personal, Invited Speaker: PharmaMar, Roche, Lilly, Pfyzer, Novartis, Eisai, Gilead, AstraZeneca, Daiichi, Seagen, Esteve, Roche. L.J. Fallowfield: Financial Interests, Personal, Invited Speaker, Genomic Health Nurses ForumMAY 2019/ DEC 2019: Genomic Health; Financial Interests, Personal, Invited Speaker, MAR 2021. Understanding the quality of survival in metastatic breast cancerOCT 2020. Novartis Virtual Summit: Novartis; Financial Interests, Personal, Advisory Board, Lilly Oncology Breast Cancer European Advisory BoardAPR 2019: Lilly; Financial Interests, Personal, Invited Speaker, NOV 2019. PrIME Masterclass in NET Neuroendocrine Tumours: prIME A Medscape Oncology Company; Financial Interests, Personal, Invited Speaker, SEP 2020. Chair national Pfizer virtual meeting: Pfizer; Financial Interests, Personal, Invited Speaker, OCT 2020. CATCH Collaborate and address treatment challenges in haemophilia Workshop Talk: Patient Engagement: Sobi; Financial Interests, Personal, Invited Speaker, SEP 2020. Communicating Risk - Virtual Consultations MSD speaker meeting: MSD; Financial Interests, Personal, Invited Speaker, OCT 2020. Financial Toxicity In Oncology From Worldwide To Italy: 3P SOLUTION; Financial Interests, Personal, Invited Speaker, NOV 19. Prosigna Event: Communicating risk to patients incorporating aspects of the recent Prosigna videos.: Veracyte; Financial Interests, Personal, Invited Speaker, SEP 2021. Step Ahead - 4th Biennial Breast Cancer Summit AZ: AstraZeneca; Financial Interests, Personal, Advisory Board: Voluntis; Financial Interests, Institutional, Funding, PI: Veracyte; Financial Interests, Institutional, Research Grant, PI: Eli Lilly, Roche, Bristol Myers Squibb. P. Auvinen: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. C. Pulido: Non-Financial Interests, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. A.S. Cvetanovic: Financial Interests, Invited Speaker, Speaker honoraria: Roche, Novartis, Pfizer, MSD Oncology, AstraZeneca, Merck. S.T. Wilks: Non-Financial Interests, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. L.A. Ribeiro: Financial Interests, Personal, Advisory Board: Novartis Farma. M. Burotto: Financial Interests, Other, Consulting fees: F. Hoffmann-La Roche Ltd., Genentech , Bristol Myers Squibb, MSD Oncology, Novartis, AstraZeneca; Financial Interests, Speaker’s Bureau: F.Hoffmann-La Roche Ltd., Genentech, MSD Oncology, Bristol Myers Squib, AstraZeneca. T. Boulet: Financial Interests, Personal, Full or part-time Employment, Employee from Parexel which is contracted by F.Hoffmann – La Roche Ltd. for statistical services in the conduct of the study: Parexel. V. Revelant: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. N. Theron: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party editing assistance from F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. P. Trask: Financial Interests, Personal, Full or part-time Employment, Employed by Genentech and hold stock in Roche.: F. Hoffmann-La Roche Ltd. L.A. Wahyudi: Non-Financial Interests, Funding, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. Z. Machackova: Financial Interests, Stocks/Shares: F. Hoffmann-La Roche Ltd. L. Stamatovic: Financial Interests, Personal, Invited Speaker: AstraZeneca, F. Hoffmann-La Roche Ltd., Novartis, Pfizer, MSD , Eli Lilly; Non-Financial Interests, Personal, Funding, Research Funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.