Background

Approximately 50% of HER2-negative breast cancers (BC) show HER2-low expression. It is unclear however whether HER2-low BC should be considered an individual biologic entity, prognostically distinct from HER2-zero BC.

Methods

Data were collected from an institutional database including all consecutive patients with BC who underwent surgery at Dana-Farber Brigham Cancer Center from 1/2016 to 3/2021. Tumors were defined as HER2-low if they had a HER2 IHC score of 1+ or 2+ with negative FISH, and HER2-zero if they had a HER2 IHC score of 0. Clinicopathologic characteristics and disease outcomes were compared between the two cohorts.

Results

5235 HER2-negative BC patients were eligible for analysis; 4429 estrogen receptor (ER)+, 67 ER-low (1-9%), 739 ER-negative. Hormone receptor(HR)-expression was significantly more common among HER2-low compared with HER2-zero BC (89.9% vs 80.9%, p<0.001). Most other clinicopathological differences were explained by the different rate of HR+ tumors. When evaluated as a continuous variable, ER expression was significantly associated with HER2 expression (p<0.001), and the rate of HER2-low tumors increased progressively with increasing ER expression (Table). Among patients receiving neoadjuvant chemotherapy (n=657), those with HER2-zero tumors had higher pCR rates compared with HER2-low (27% vs 17%, p=0.002). However, statistical difference was lost when separately analyzing HR+ (8% vs 14%, p=0.078), ER-low (25% vs 38.9%, p=0.46), HR+ without ER-low (6.9% vs 10.4%, p=0.277), TNBC (30.8% vs 35.4%, p=0.40) and when adjusting for confounders. No difference in disease-free survival or overall survival was observed among patients with HR+ tumors or TNBC depending on HER2-low expression. Table: 1MO

Proportion of tumors with HER2-low versus HER2-zero expression according to tumor subtype and ER expression

Conclusions

Our results do not support the interpretation of HER2-low BC as a distinct biologic subtype. HER2-low expression is continuously associated with the level of ER expression. ER-low tumors are enriched among HER2-zero cases and may confound prognostic analyses.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Tarantino: Financial Interests, Personal, Advisory Role: AstraZeneca. N.U. Lin: Financial Interests, Institutional, Other: Genentech, Merck, Pfizer; Financial Interests, Personal, Other: Seattle Genetics; Financial Interests, Personal, Advisory Role: Puma, Daiichi Sankyo, AstraZeneca, Denali Therapeutics, California Institute for Regenerative Medicine, Prelude Therapeutics. T.A. King: Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Advisory Role: PrecisCA Cancer Information Service. E.A. Mittendorf: Financial Interests, Personal, Advisory Role: Exact Science, Bristol Myers Squib, Genentech/Roche, Lilly, Merck. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly, Pfizer, Novartis, Merck, Gilead, Genentech/Roche, Eisai, Sanofi, Seagen, Daiichi Sankyo, 4D Pharma, Puma; Financial Interests, Personal, Other, Consultant: Nektar, NanoString, Athenex, Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, OncoPep, OncoSec, Certara, Mersana Therapeutics, Ellipses Pharma, G1 Therapeutics; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Invited Speaker, Invited Speaker for Pharma Supported Educational Activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks, Zentalis, Reveal Genomics, OncXerna; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. All other authors have declared no conflicts of interest.

Background

Changes occurring in host-associated microbial communities (i.e. microbiota) may modulate responses to checkpoint blockade immunotherapy. We previously showed that anti-programmed cell death 1 protein P added to microtubule-targeting chemotherapy E has an encouraging antitumor activity in HR+ MBC pts regardless of programmed death-ligand 1 status. The CALADRIO study assessed the impact of gut and oral microbiota on clinical outcome of pts from the KELLY trial.

Methods

The phase 2 KELLY trial investigated the efficacy and safety of P plus E in 44 pts with pre-treated, HR+, HER2-negative, locally recurrent inoperable or MBC (NCT03222856). Fecal and saliva samples were prospectively collected at baseline (BL), after 3 cycles, and end of treatment from a subset of pts. Tumor response was grouped into clinical benefit (CB; complete or partial responses, or stable disease [SD] ≥24 weeks) and no CB (SD <24 weeks or progressive disease) as per RECIST 1.1. Shotgun metagenomic and 16S rRNA gene sequencing were used to characterize fecal and saliva microbiota profiles, respectively. Microbiota data were analyzed using MEGAHIT, LEfSe, Wilcoxon ranked sum, and PERMANOVA methods.

Results

A total of 58 fecal and 68 saliva samples were collected. Overall P+E did not cause significant gut or oral microbiota perturbations, indicating any drug-related microbial toxicity. Across all pts, dominant gut microbiota genera included Bacteroides and Faecalibacterium, with a common oral microbe, Prevotella, also present. LeFSe analysis suggested CB was driven in part by gut-associated Bacteroides fragilis and oral-associated Streptococcus with an abundance ≥50%. Pts experiencing CB had gut and oral microbiota richness at BL and a decrease over treatment potentially related to the antibiotic usage. Several typical oral microbes in both saliva and fecal samples were also observed, suggesting a potential translocation along the oral-gut axis.

Conclusions

These preliminary findings suggest potential avenues for downstream microbiota pts stratification before commencement of treatment. Further investigation is required in larger cohorts.

Clinical trial identification

NCT03222856.

Legal entity responsible for the study

MEDSIR.

Funding

MEDSIR.

Disclosure

M. Gion Cortes: Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: Pfizer. J.M. Perez Garcia: Non-Financial Interests, Personal, Advisory Role: Roche; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Sponsor/Funding: Roche. A. Prat: Non-Financial Interests, Personal, Full or part-time Employment: Novoartis; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Sponsor/Funding: Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, Amgen, Guardant Health; Non-Financial Interests, Personal, Advisory Role: Amgen, Roche, Novartis, Pfizer, Bristol Myers Squibb, Boehringer, Puma, Oncolytics Biotech, Daiichi Sankyo, AbbVie, AstraZeneca, NanoString Technologies (to the Institution); Financial Interests, Institutional, Funding: Roche, Novartis, Incyte, Puma Biotechnology; Financial Interests, Personal, Ownership Interest: Patents:- PCT/EP2016/080056, - WO/2018/096191, US 63/023785, HER2DX (filing); Financial Interests, Personal, Sponsor/Funding: Daiichi Sankyo; Other, Personal, Other: Oncolytics, Peptomyc S.L. A. Llombart Cussac: Non-Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD;; Financial Interests, Personal, Stocks/Shares: MEDSIR, Initia-Research; Non-Financial Interests, Institutional, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, GenomicHealth, GSK; Non-Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Funding: Roche, Foundation Medicine, Pierre Fabre, Agendia; Financial Interests, Personal, Sponsor/Funding: Roche, Lilly, Novartis, Pfizer, AstraZeneca. M. Mancino: Financial Interests, Personal and Institutional, Full or part-time Employment: MEDSIR. J. Cortés: Non-Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology.; Financial Interests, Personal, Sponsor/Funding: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo.; Financial Interests, Personal and Institutional, Funding: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London.; Financial Interests, Personal, Stocks/Shares: MEDSIR. A. Malfettone: Financial Interests, Personal and Institutional, Full or part-time Employment: MEDSIR. All other authors have declared no conflicts of interest.

Background

Establishing biobanking in cancer research is important for health research infrastructure to collect, store, process, and distribute high-quality human biological samples and associated data. The Biobank for Translational Medicine (B4MED) Unit at the European Institute of Oncology (IEO) is a landmark in this field. The aim of this analysis was to retrospectively examine the evolution of biobank activity for breast cancer research during the 10 years since the B4MED foundation.

Methods

All B4MED activities are controlled and tracked by Nautilus Laboratory Information Management System, a management system integrated with IEO medical records database. The files of B4MED were interrogated for the number of samples associated with patients treated for breast cancer at IEO, including their storage and use since the beginning of B4MED. All clinicopathologic characteristics, including histological subtype, grade, and stage, were retrieved into a pseudo-anonymized database. To extract the data, we performed a query with the following keywords: Breast, Carcinoma, and Primary.

Results

A total of 3,858 breast cancers and integrated clinicopathologic data were collected in our biobank (2012-2022). The samples, stored at -80°C, included tumor (n=3,858), matched non-neoplastic tissues (n=2,101; 55%), and biofluids (n=3,423; 89%), i.e. blood, serum, and plasma. For 1,774 (45%) patients both the normal tissue and blood samples were stored. Subtypes included 3,188 (82.6%) invasive carcinoma of no special type, 428 (11.1%) lobular, 134 (3.5%) mixed ductal-lobular, and 84 (2.2%) special types. Grade, stage, and molecular subtypes were available for all patients. Biomarkers were carefully annotated (e.g. we were able to retrieve 1,478 HER2-low breast cancers samples). All patients signed the Scientific Research Participation Agreement.

Conclusions

B4MED at IEO is an invaluable source of biomaterials that in the last decade led to remarkable scientific innovations related to new biomarkers and novel drugs, for increasingly personalized treatment strategies designed for breast cancer patients. The next challenge is to integrate digital and molecular pathology data to take advantage of machine learning protocols for next-generation biobanking.

Legal entity responsible for the study

The authors.

Funding

European Institute of Oncology and Italian Ministries of Health and Research.

Disclosure

All authors have declared no conflicts of interest.

Background

Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) but knowledge regarding their use in clinical practice is scarce. PROCURE Project preliminary results were presented at ESMO Breast Virtual Congress 2021 (Abstract 549). Final results regarding the panelist opinion on the utility of BCMS in treatment decision making for different eBC patient profiles are now available.

Methods

The Delphi questionnaire developed by the Scientific Committee was administered twice to 133 experts across 11 European countries. The questionnaire included 5 sections: 1) Panelists’ profile and experience with BCMS, 2) Current clinical practice in eBC and use of BCMS, 3) Panelists’ opinion on the utility of the BCMS in eBC according to patient profiles, 4) Agreement with a set of recommendations on the use of BCMS in clinical practice and 5) Identification of unmet needs and future applications of BCMS. 70% agreement was used to determine consensus on a topic.

Results

Panelists agreed on the clinical utility of BC molecular intrinsic subtypes for prognosis or residual risk of recurrence with standard of care in eBC HR+ (76%) and to identify a group of patients that can safely avoid chemotherapy (75%). Additionally, panelist agreed on the importance of BCMS prognostic results when deciding chemotherapy in the adjuvant setting in eBC patients with node negative (88%) or with 1 to 3 positive lymph nodes (75%). Regarding BCMS use in different patient profiles, panelists agreed on their utility in post-menopausal eBC patients (90%) and on the absence of utility in the metastatic setting (74%), in eBC patients with an HER2 overexpressed profile (82%) and in eBC triple negative (TN) (74%). Also, just 27% of the panelist considered that BCMS can be useful in the neoadjuvant setting.

Conclusions

The low percentage of panelists performing BCMS in the neoadjuvant setting, the misconception regarding their predictive value on chemotherapy benefits and the fact that some experts consider BCMS useful in TN, HER2+ eBC or in the metastatic setting show that there is a need of education on how to interpret BCMS results.

Legal entity responsible for the study

Veracyte Inc.

Funding

Veracyte Inc.

Disclosure

G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Ellipsis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Veracyte; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS; Financial Interests, Institutional, Funding, Phase I studies: Novartis; Financial Interests, Institutional, Funding, Phase I studies: AstraZeneca; Financial Interests, Institutional, Funding, Phase I studies: Daiichi Sankyo; Financial Interests, Institutional, Funding, Phase I studies: Roche; Financial Interests, Institutional, Funding, Phase I studies: Blueprint Medicine; Financial Interests, Institutional, Funding, Phase I studies: Kymab; Financial Interests, Institutional, Funding, Phase I studies: Astellas; Financial Interests, Institutional, Funding, Phase I studies: Sanofi; Financial Interests, Institutional, Funding, Phase I studies: Philogen; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Astellas/Medivation; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celgene; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Other, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: GE Oncology; Financial Interests, Personal, Other, Consultancy: Genentech; Financial Interests, Personal, Other, Consultancy: GlaxoSmithKline; Financial Interests, Personal, Other, Consultancy: Macrogenics; Financial Interests, Personal, Other, Consultancy: Medscape; Financial Interests, Personal, Other, Consultancy: Merck-Sharp; Financial Interests, Personal, Other, Consultancy: Merus BV; Financial Interests, Personal, Other, Consultancy: Mylan; Financial Interests, Personal, Other, Consultancy: Mundipharma; Financial Interests, Personal, Other, Consultancy: Novartis; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy: Pierre Fabre; Financial Interests, Personal, Other, Consultancy: prIME Oncology; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Sanofi; Financial Interests, Personal, Other, Consultancy: Samsung Bioepis; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Other, Consultancy: Teva; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: Fresenius GmbH; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Nektar Therapeutics; Financial Interests, Institutional, Invited Speaker: Nerviano; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Medigene; Financial Interests, Institutional, Invited Speaker: MedImmune; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Millenium; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Sanofi-Aventis; Financial Interests, Institutional, Invited Speaker: Sonus; Financial Interests, Institutional, Invited Speaker: Taiho Oncology; Financial Interests, Institutional, Invited Speaker: Tesaro; Financial Interests, Institutional, Invited Speaker: Tigris; Financial Interests, Institutional, Invited Speaker: Wilex; Financial Interests, Institutional, Invited Speaker: Wyeth; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO; Non-Financial Interests, Member: ESO; Non-Financial Interests, Member: EORTC; Non-Financial Interests, Member: BCG; Non-Financial Interests, Member: IBCSG; Non-Financial Interests, Member: SOLTI; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR; Non-Financial Interests, Member: EACR; Non-Financial Interests, Member: SIS; Non-Financial Interests, Member: ASPIC. M.I. Gnant: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Other, Consulting on scientific matters: LifeBrain; Financial Interests, Personal, Expert Testimony: Veracyte; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Full or part-time Employment: ABCSG GmbH; Financial Interests, Invited Speaker: Pfizer; Other, Spouse is employed by: Sandoz. N. Harbeck: Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Daiichi Sankyo; Financial Interests, Invited Speaker: Exact Sciences; Financial Interests, Invited Speaker: Gilead; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: MSD; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker Pierre Fabre; Financial Interests, Invited Speaker: Pfizer; Financial Interests, Invited Speaker: Roches; Financial Interests, Invited Speaker: Seagen; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: Gilead; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Sandoz; Financial Interests, Advisory Board: Seagen. J. King: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Seagen; Financial Interests, Personal, Speaker’s Bureau: Novartis. A. Laenkholm: Financial Interests, Advisory Board: Merck; Financial Interests, Advisory Board: Agilent; Financial Interests, Funding: Novartis; Financial Interests, Funding: Roche. F. Penault-Llorca: Financial Interests, Funding: Veracyte; Financial Interests, Funding: Myriad; Financial Interests, Funding: Illumina; Financial Interests, Advisory Board: Veracyte; Financial Interests, Advisory Board: Exact Science; Financial Interests, Advisory Board: Myriad; Financial Interests, Advisory Board: Agendia; Financial Interests, Advisory Board: Illumina; Financial Interests, Other: Myriad; Financial Interests, Other: Veracyte. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research:: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Personal, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: NanoString; Financial Interests, Institutional, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno. Research; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Institutional, Other, Contracted research: Astellas; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Clinical trials: Amgen; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation.

Background

The approval of abemaciclib (abema) for the adjuvant treatment of patients with high-risk, lymph node (LN)+, hormone-receptor (HR)+ breast cancer (BC) has reshaped treatment algorithms for this disease. However, the real-world features of BC patients eligible for abema remain unknown.

Methods

We reviewed data of all consecutive patients with HR+ BC who underwent surgery at Dana-Farber Brigham Cancer Center from 1/2016 to 3/2021. According to the latest NCCN guidelines, patients were eligible for abema if they had either: (i) 1-3+ LN and tumors either ≥5 cm or grade 3, or (ii) ≥4+ LN. Clinicopathologic features of this population were compared with HR+ BC patients not otherwise meeting eligibility criteria for abema.

Results

Of 4,496 HR+ patients in the database, 499 (11.1%) were eligible for adjuvant abema, whereas 3,997 did not meet eligibility criteria. Compared with non-eligible patients, those eligible for adjuvant abema were significantly younger (median age 53 vs 61, p<0.001), more often pre-menopausal (52% vs 30.3%, p<0.001) or BRCA2-mutant (10.9% vs 2.9%, p=0.002), more often had lobular tumors (20.8% vs. 13.8%, p<0.001) and high-risk (≥26) OncotypeDX recurrence scores (30.7% vs 14.4%, p<0.001). As expected, there were significant differences in receipt of treatment, with abema-eligible patients more often receiving (neo)adjuvant chemotherapy (77.8% vs 11.6%, p<0.001), neoadjuvant endocrine treatment (11.2% vs 3.7%, p<0.001), total mastectomy (64.7% vs 24.3%, p<0.001) and axillary LN dissection (76.0% vs 6.2%, p<0.001). Among eligible patients receiving neoadjuvant chemotherapy (n=202), none experienced a pathological complete response, 3 experienced a residual cancer burden (RCB) score of I, and the remaining patients had extensive residual disease at surgery (RCB II-III). After a median follow up of 10 months, 2-year distant disease-free survival of eligible pts was 90.9% and 2-year overall survival was 96.4%.

Conclusions

Patients eligible for adjuvant abema are younger, more often BRCA2-mutant and more often harbor lobular tumors compared to non-eligible patients. Response to chemotherapy in this cohort appears poor. Our real-world data support recently approved adjuvant treatment strategies to include abema and olaparib.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Tarantino: Financial Interests, Personal, Financial Interests, Fee for consulting/advisory role: AstraZeneca. E.A. Mittendorf: Financial Interests, Personal, Invited Speaker: Bristol Myers Squib; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: Genentech/Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck. T.A. King: Financial Interests, Personal, Financial Interests: Exact Sciences; Financial Interests, Personal, Financial Interests: PrecisCA cancer information service. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Ellipsis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Veracyte; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS; Financial Interests, Institutional, Funding, Phase I studies: Novartis; Financial Interests, Institutional, Funding, Phase I studies: AstraZeneca; Financial Interests, Institutional, Funding, Phase I studies: Daiichi Sankyo; Financial Interests, Institutional, Funding, Phase I studies: Roche; Financial Interests, Institutional, Funding, Phase I studies: Blueprint Medicine; Financial Interests, Institutional, Funding, Phase I studies: Kymab; Financial Interests, Institutional, Funding, Phase I studies: Astellas; Financial Interests, Institutional, Funding, Phase I studies: Sanofi; Financial Interests, Institutional, Funding, Phase I studies: Philogen; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Gilead; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Genentech/Roche; Financial Interests, Personal, Other, Consultant: Nektar; Financial Interests, Personal, Other, Consultant: NanoString; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Eisai; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Sanofi; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Seagen; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Athenex; Financial Interests, Personal, Advisory Board, Ad board participant: OncoPep; Financial Interests, Personal, Advisory Board, Ad board participant: OncoSec; Financial Interests, Personal, Advisory Board, Ad board participant: Certara; Financial Interests, Personal, Advisory Board, Ad board participant: Mersana Therapeutics; Financial Interests, Personal, Advisory Board, Ad board participant: Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Puma; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation: OncXerna; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Seagen; Financial Interests, Institutional, Funding: Odonate; Financial Interests, Personal and Institutional, Invited Speaker: CytomX; Financial Interests, Institutional, Funding: Cyclacel; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Gilead; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Nektar; Financial Interests, Institutional, Funding: Genentech/Roche. All other authors have declared no conflicts of interest.

Background

In DESTINY-Breast03 (NCT03529110), T-DXd showed superior progression-free survival by BICR vs T-DM1 (HR, 0.28 [95% CI, 0.22-0.37]; P < 0.001) and manageable safety in pts with HER2+ MBC. PRO measures incorporate pts’ perspective in clinical trials to assess effect of treatment on health-related quality of life (QoL). Here, PROs and hospitalization rate for T-DXd vs T-DM1 (May 21, 2021, data cutoff) are reported.

Methods

Pts with HER2+ (IHC 3+ or IHC 2+/ISH+) MBC whose disease progressed on or after trastuzumab and a taxane were assigned 1:1 to T-DXd or T-DM1. PRO endpoints were assessed before infusion on day 1 of the first 3 21-day cycles, then every 2 cycles, at end of treatment, at 40-days’ follow-up, then every 3 months until end of follow-up; endpoints included European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ-C30; primary variable: global health status [GHS]/QoL scale score) and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale (VAS). Analyses included change from baseline (CFB) and time to definitive deterioration (TDD). Hospitalization-related endpoints were also measured.

Results

Compliance for questionnaires was >97% at baseline and >80% for cycles 3-29. QLQ-C30 baseline GHS scores recorded for T-DXd (n = 253) and T-DM1 (n = 260) were similar. At end of treatment, mean CFB was not meaningfully different vs baseline (<10-point CFB) in both arms. Median TDD of QLQ-C30 GHS was 9.7 mo for T-DXd vs 8.3 mo for T-DM1 (HR, 0.88 [95% CI, 0.70-1.11]), and all prespecified QLQ-C30 subscales presented longer TDD with T-DXd, including emotional functioning (HR, 0.69 [95% CI, 0.53-0.89]) and pain (HR, 0.75 [95% CI, 0.59-0.95]). Median TDD of EQ-5D-5L VAS was 13.2 mo for T-DXd vs 8.5 mo for T-DM1 (HR, 0.77 [95% CI, 0.61-0.98]). With T-DXd vs T-DM1, 18 pts (6.9%) vs 19 pts (7.2%) were hospitalized; median time to first hospitalization was 219.5 vs 60.0 days, respectively.

Conclusions

The improved efficacy and manageable toxicity reported previously for T-DXd, together with this evidence of maintained or improved QoL supports the overall benefit of T-DXd for pts with HER2+ MBC.

Clinical trial identification

NCT03529110.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Marianna B. Johnson, PhD, and Eileen McIver, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc., AstraZeneca.

Disclosure

G. Curigliano: Financial Interests, Personal, Other, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Advisory Board, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer, Roche; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Officer: ESMO, LILT, EUSOMA; Financial Interests, Personal, Other: National Health Council. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Rosenlund: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Janek: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Cathcart: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Liu: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. P.A. Fasching: Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Research Grant: Cepheid, BioNTech; Financial Interests, Personal, Officer: TRIO. H. Iwata: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Chugai, AstraZeneca, Sanofi, Lilly, MSD, Pfizer; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer.

Background

Palbociclib (PB), the first clinically available oral CDK4/6 inhibitor, in combination with endocrine therapy has become standard of care for HR+/HER2– advanced/metastatic breast cancer (MBC). This study compared overall survival (OS) of MBC patients treated with first-line PB+AI vs AI alone in US routine clinical practices.

Methods

We conducted a retrospective analysis of HR+/HER2– MBC patients in the Flatiron Health longitudinal database, representing more than 2.4 million actively treated cancer patients in the US. Between February 2015 and March 2020, 2888 postmenopausal MBC women and men aged ≥18 years started first-line PB+AI or AI therapy. Patients were evaluated from start of PB+AI or AI to September 2020, death, or last visit, whichever came first. Both stabilized inverse probability treatment weighting (sIPTW) and propensity score matching (PSM) statistical methods were used to balance patient characteristics.

Results

Of the eligible patients (1324 with PB+AI and 1564 with AI), median age was 70.0 years, 67.8% were white, 34.8% had de novo MBC, 29.4% had lung or liver involvement, 38.7% had bone-only disease. Median OS in PB+AI vs AI was 53.4 (95%CI=48.7-58.6) vs 40.4 (95%CI=36.3-44.9) months (mo) (HR=0.67, 95%CI=0.60-0.76, p<.0001), respectively. After sIPTW, median OS was 49.1 mo (95%CI=45.2-57.7) for PB+AI vs 43.2 mo (95%CI=37.6-48.0) for AI (HR=0.76, 95%CI=0.65-0.87, p<.0001). After 1:1 PSM, median OS was 57.8 mo (95%CI=47.2—NR) with matched PB+AI vs 43.5 mo (95%CI=37.6-48.9) with matched AI (HR=0.72, 95%CI=0.62-0.83, p<.0001). Table presents key patient characteristics and OS results.

Conclusions

This largest to date real-world comparative effectiveness study demonstrated that palbociclib +AI was significantly associated with prolonged overall survival vs AI alone, supporting first-line palbociclib plus AI as a standard of care for HR+/HER2– MBC patients. Table: 169P

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Merck; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: Roche; Financial Interests, Institutional, Financial Interests: Daiichi Sankyo; Financial Interests, Institutional, Financial Interests: Seattle Genetics; Financial Interests, Institutional, Financial Interests: Macrogenics; Financial Interests, Institutional, Financial Interests: Sermonix; Financial Interests, Institutional, Financial Interests: Boehringer Ingelheim; Financial Interests, Institutional, Financial Interests: Polyphor; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Ayala; Financial Interests, Institutional, Financial Interests: Gilead; Financial Interests, Institutional, Financial Interests: Puma; Financial Interests, Institutional, Financial Interests: Samsung; Financial Interests, Institutional, Financial Interests: Mylan. A. Brufsky, X. Liu, B. Li, L. McRoy, C. Chen: Financial Interests, Institutional, Financial Interests: Pfizer Inc. R.M. Layman: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: GlaxoSmithKline; Financial Interests, Institutional, Financial Interests: Zentalis. M. Cristofanilli: Financial Interests, Institutional, Financial Interests: Merck; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Menarini; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: G1 Therapeutics; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Sermonix; Financial Interests, Institutional, Financial Interests: Foundation Medicine. M.A. Torres: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Genentech; Financial Interests, Institutional, Financial Interests: Centers for Disease Control; Financial Interests, Institutional, Financial Interests: Oncohealth; Financial Interests, Institutional, Financial Interests: MJH Life Sciences. G. Curigliano: Financial Interests, Institutional, Financial Interests: Seagen; Financial Interests, Institutional, Financial Interests: Roche; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Lilly; Financial Interests, Institutional, Financial Interests: Daiichi Sankyo; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Pfizer; Financial Interests, Institutional, Financial Interests: Sanofi; Financial Interests, Institutional, Financial Interests: Pierre Fabre; Financial Interests, Institutional, Financial Interests: Gilead. R.S. Finn: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: Novartis. A. Demichele: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Calithera; Financial Interests, Institutional, Financial Interests: Genentech.

Background

Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) but knowledge regarding their use in clinical practice is scarce. PROCURE Project preliminary results were presented at ESMO Breast Virtual Congress 2021 (Abstract 549). Final results regarding the panelist opinion on the utility of BCMS in treatment decision making for different eBC patient profiles are now available.

Methods

The Delphi questionnaire developed by the Scientific Committee was administered twice to 133 experts across 11 European countries. The questionnaire included 5 sections: 1) Panelists’ profile and experience with BCMS, 2) Current clinical practice in eBC and use of BCMS, 3) Panelists’ opinion on the utility of the BCMS in eBC according to patient profiles, 4) Agreement with a set of recommendations on the use of BCMS in clinical practice and 5) Identification of unmet needs and future applications of BCMS. 70% agreement was used to determine consensus on a topic.

Results

Panelists agreed on the clinical utility of BC molecular intrinsic subtypes for prognosis or residual risk of recurrence with standard of care in eBC HR+ (76%) and to identify a group of patients that can safely avoid chemotherapy (75%). Additionally, panelist agreed on the importance of BCMS prognostic results when deciding chemotherapy in the adjuvant setting in eBC patients with node negative (88%) or with 1 to 3 positive lymph nodes (75%). Regarding BCMS use in different patient profiles, panelists agreed on their utility in post-menopausal eBC patients (90%) and on the absence of utility in the metastatic setting (74%), in eBC patients with an HER2 overexpressed profile (82%) and in eBC triple negative (TN) (74%). Also, just 27% of the panelist considered that BCMS can be useful in the neoadjuvant setting.

Conclusions

The low percentage of panelists performing BCMS in the neoadjuvant setting, the misconception regarding their predictive value on chemotherapy benefits and the fact that some experts consider BCMS useful in TN, HER2+ eBC or in the metastatic setting show that there is a need of education on how to interpret BCMS results.

Legal entity responsible for the study

Veracyte Inc.

Funding

Veracyte Inc.

Disclosure

G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Ellipsis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Veracyte; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS; Financial Interests, Institutional, Funding, Phase I studies: Novartis; Financial Interests, Institutional, Funding, Phase I studies: AstraZeneca; Financial Interests, Institutional, Funding, Phase I studies: Daiichi Sankyo; Financial Interests, Institutional, Funding, Phase I studies: Roche; Financial Interests, Institutional, Funding, Phase I studies: Blueprint Medicine; Financial Interests, Institutional, Funding, Phase I studies: Kymab; Financial Interests, Institutional, Funding, Phase I studies: Astellas; Financial Interests, Institutional, Funding, Phase I studies: Sanofi; Financial Interests, Institutional, Funding, Phase I studies: Philogen; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Astellas/Medivation; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celgene; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Other, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: GE Oncology; Financial Interests, Personal, Other, Consultancy: Genentech; Financial Interests, Personal, Other, Consultancy: GlaxoSmithKline; Financial Interests, Personal, Other, Consultancy: Macrogenics; Financial Interests, Personal, Other, Consultancy: Medscape; Financial Interests, Personal, Other, Consultancy: Merck-Sharp; Financial Interests, Personal, Other, Consultancy: Merus BV; Financial Interests, Personal, Other, Consultancy: Mylan; Financial Interests, Personal, Other, Consultancy: Mundipharma; Financial Interests, Personal, Other, Consultancy: Novartis; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy: Pierre Fabre; Financial Interests, Personal, Other, Consultancy: prIME Oncology; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Sanofi; Financial Interests, Personal, Other, Consultancy: Samsung Bioepis; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Other, Consultancy: Teva; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: Fresenius GmbH; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Nektar Therapeutics; Financial Interests, Institutional, Invited Speaker: Nerviano; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Medigene; Financial Interests, Institutional, Invited Speaker: MedImmune; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Millenium; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Sanofi-Aventis; Financial Interests, Institutional, Invited Speaker: Sonus; Financial Interests, Institutional, Invited Speaker: Taiho Oncology; Financial Interests, Institutional, Invited Speaker: Tesaro; Financial Interests, Institutional, Invited Speaker: Tigris; Financial Interests, Institutional, Invited Speaker: Wilex; Financial Interests, Institutional, Invited Speaker: Wyeth; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO; Non-Financial Interests, Member: ESO; Non-Financial Interests, Member: EORTC; Non-Financial Interests, Member: BCG; Non-Financial Interests, Member: IBCSG; Non-Financial Interests, Member: SOLTI; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR; Non-Financial Interests, Member: EACR; Non-Financial Interests, Member: SIS; Non-Financial Interests, Member: ASPIC. M.I. Gnant: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Other, Consulting on scientific matters: LifeBrain; Financial Interests, Personal, Expert Testimony: Veracyte; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Full or part-time Employment: ABCSG GmbH; Financial Interests, Invited Speaker: Pfizer; Other, Spouse is employed by: Sandoz. N. Harbeck: Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Daiichi Sankyo; Financial Interests, Invited Speaker: Exact Sciences; Financial Interests, Invited Speaker: Gilead; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: MSD; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker Pierre Fabre; Financial Interests, Invited Speaker: Pfizer; Financial Interests, Invited Speaker: Roches; Financial Interests, Invited Speaker: Seagen; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: Gilead; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Sandoz; Financial Interests, Advisory Board: Seagen. J. King: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Seagen; Financial Interests, Personal, Speaker’s Bureau: Novartis. A. Laenkholm: Financial Interests, Advisory Board: Merck; Financial Interests, Advisory Board: Agilent; Financial Interests, Funding: Novartis; Financial Interests, Funding: Roche. F. Penault-Llorca: Financial Interests, Funding: Veracyte; Financial Interests, Funding: Myriad; Financial Interests, Funding: Illumina; Financial Interests, Advisory Board: Veracyte; Financial Interests, Advisory Board: Exact Science; Financial Interests, Advisory Board: Myriad; Financial Interests, Advisory Board: Agendia; Financial Interests, Advisory Board: Illumina; Financial Interests, Other: Myriad; Financial Interests, Other: Veracyte. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research:: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Personal, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: NanoString; Financial Interests, Institutional, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno. Research; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Institutional, Other, Contracted research: Astellas; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Clinical trials: Amgen; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation.

Background

In DESTINY-Breast03 (NCT03529110), T-DXd showed superior progression-free survival by BICR vs T-DM1 (HR, 0.28 [95% CI, 0.22-0.37]; P < 0.001) and manageable safety in pts with HER2+ MBC. PRO measures incorporate pts’ perspective in clinical trials to assess effect of treatment on health-related quality of life (QoL). Here, PROs and hospitalization rate for T-DXd vs T-DM1 (May 21, 2021, data cutoff) are reported.

Methods

Pts with HER2+ (IHC 3+ or IHC 2+/ISH+) MBC whose disease progressed on or after trastuzumab and a taxane were assigned 1:1 to T-DXd or T-DM1. PRO endpoints were assessed before infusion on day 1 of the first 3 21-day cycles, then every 2 cycles, at end of treatment, at 40-days’ follow-up, then every 3 months until end of follow-up; endpoints included European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ-C30; primary variable: global health status [GHS]/QoL scale score) and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale (VAS). Analyses included change from baseline (CFB) and time to definitive deterioration (TDD). Hospitalization-related endpoints were also measured.

Results

Compliance for questionnaires was >97% at baseline and >80% for cycles 3-29. QLQ-C30 baseline GHS scores recorded for T-DXd (n = 253) and T-DM1 (n = 260) were similar. At end of treatment, mean CFB was not meaningfully different vs baseline (<10-point CFB) in both arms. Median TDD of QLQ-C30 GHS was 9.7 mo for T-DXd vs 8.3 mo for T-DM1 (HR, 0.88 [95% CI, 0.70-1.11]), and all prespecified QLQ-C30 subscales presented longer TDD with T-DXd, including emotional functioning (HR, 0.69 [95% CI, 0.53-0.89]) and pain (HR, 0.75 [95% CI, 0.59-0.95]). Median TDD of EQ-5D-5L VAS was 13.2 mo for T-DXd vs 8.5 mo for T-DM1 (HR, 0.77 [95% CI, 0.61-0.98]). With T-DXd vs T-DM1, 18 pts (6.9%) vs 19 pts (7.2%) were hospitalized; median time to first hospitalization was 219.5 vs 60.0 days, respectively.

Conclusions

The improved efficacy and manageable toxicity reported previously for T-DXd, together with this evidence of maintained or improved QoL supports the overall benefit of T-DXd for pts with HER2+ MBC.

Clinical trial identification

NCT03529110.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Marianna B. Johnson, PhD, and Eileen McIver, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc., AstraZeneca.

Disclosure

G. Curigliano: Financial Interests, Personal, Other, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Advisory Board, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer, Roche; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Officer: ESMO, LILT, EUSOMA; Financial Interests, Personal, Other: National Health Council. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Rosenlund: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Janek: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Cathcart: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Liu: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. P.A. Fasching: Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Research Grant: Cepheid, BioNTech; Financial Interests, Personal, Officer: TRIO. H. Iwata: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Chugai, AstraZeneca, Sanofi, Lilly, MSD, Pfizer; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer.