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

Abemaciclib is the first and only approved CDK4 & 6 inhibitor in the adjuvant setting for certain types of HR+, HER2-, node-positive, high-risk early breast cancer (EBC). Patient (Pts) with HR+, HER2- tumors who are premenopausal (preM) may have a different tumor biology and response to endocrine therapy (ET) than postmenopausal (postM) pts, warranting analysis of the prespecified subgroup within monarchE.

Methods

Randomized (1:1) pts received adjuvant ET +/- abemaciclib for 2 years (yrs) plus at least 3 yrs of ET as clinically indicated. Menopausal status (preM vs. postM) at diagnosis was a predefined stratification factor. Standard ET (tamoxifen or an aromatase inhibitor), with or without additional GnRH, was determined by physician’s choice. Baseline disease characteristics and ET choice were described at ESMO, 2021. Efficacy and safety results of abemaciclib + ET vs. ET alone including invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) were assessed by menopausal status with a data cut-off date on 1 April 2021, at a median follow-up of 27 months.

Results

Among randomized pts, 2451 (43.5%) were preM and 3181 (56.4%) postM. Treatment benefit was consistent in both menopausal status subgroups, with numerically greater effect size in preM subgroup compared to postM subgroup (Table). For preM pts, abemaciclib + ET resulted in a 42.7% and 40.8% reduction in risk of developing an IDFS and DRFS event, respectively. The absolute improvement at 3 yrs was 5.7% for IDFS and 4.4% for DRFS rates. The safety profile for preM pts was consistent with the safety population. Table: 63P

Efficacy data by menopausal status

Conclusions

Abemaciclib + ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS vs. ET alone regardless of menopausal status, with a numerically greater benefit in the preM population. Safety data in preM pts is consistent with the overall safety profile of abemaciclib.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Medical writing support was provided by Trish Huynh (Eli Lilly and Company, IN, USA).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

S. Paluch-Shimon: Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Roche; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Pfizer; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Novartis; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Exact sciences; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Eli Lilly; Financial Interests, Institutional, Other, Advisory board, speaker's bureau, consultancy: Medison; Financial Interests, Personal and Institutional, Research Grant, Research grant for an RFP independent research put out by SPCC and Pfizer: SPCC (Shared Progress in Cancer Care). P. Neven: Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Roularta Belgium; Financial Interests, Personal, Other, Lecture fees: Eli Lilly; Financial Interests, Personal, Other, Lecture fees: Novartis; Financial Interests, Personal, Other, Lecture fees: Pfizer; Financial Interests, Personal, Other, Lecture fees: AstraZeneca. J. Huober: Financial Interests, Research Grant: Celgene; Financial Interests, Research Grant: Novartis; Financial Interests, Research Grant: Hexal; Financial Interests, Research Grant: Eli Lilly and Company; Financial Interests, Other, Honoraria: Eli Lilly and Company; Financial Interests, Other, Honoraria: Novartis; Financial Interests, Other, Honoraria: Roche; Financial Interests, Other, Honoraria: Pfizer; Financial Interests, Other, Honoraria: AstraZeneca; Financial Interests, Other, Honoraria: MSD; Financial Interests, Other, Honoraria: Celgene; Financial Interests, Other, Honoraria: Eisai; Financial Interests, Other, Honoraria: AbbVie; Financial Interests, Other, Honoraria: Seagen; Financial Interests, Other, Honoraria: Gilead; Financial Interests, Advisory Role: Eli Lilly and Company; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Hexal; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: AbbVie; Financial Interests, Advisory Role: Seagen; Financial Interests, Advisory Role: Gilead; Financial Interests, Other, Travel expenses: Roche; Financial Interests, Other, Travel expenses: Pfizer; Financial Interests, Other, Travel expenses: Novartis; Financial Interests, Other, Travel expenses: Celgene; Financial Interests, Other, Travel expenses: Daiichi. Z. Jiang: Financial Interests, Advisory Board: Eli Lilly and Company; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: AbbVie; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Amgen; Financial Interests, Advisory Board: Glaxo Smith Kline; Financial Interests, Advisory Board: Boehringer Ingelheim. M.P. Goetz: Other, Institutional, Other, Consulting: Eagle Pharmaceuticals; Other, Institutional, Other, Consulting: Eli Lilly and Company; Other, Institutional, Other, Consulting: Biovica; Other, Institutional, Other, Consulting: Novartis; Other, Institutional, Other, Consulting: Sermonix; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Research Grant: Eli Lilly and Company; Other, Institutional, Other, Consulting: Pfizer; Other, Institutional, Other, Consulting: Biotheranostics; Financial Interests, Institutional, Research Grant: Sermonix; Other, Institutional, Other, Consulting: AstraZeneca; Other, Institutional, Other, Consulting: Blueprint Medicines; Other, Personal, Other, Consulting: Research to Practice; Other, Personal, Other, Consulting: Clinical Education Alliance. C. Shimizu: Financial Interests, Research Grant: Eli Lilly and Company; Financial Interests, Personal, Invited Speaker, Lecture Fee: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture Fee: Chugai; Financial Interests, Personal, Invited Speaker, Lecture Fee: Taiho; Financial Interests, Personal, Other, Honoraria: AstraZeneca. C. Huang: Financial Interests, Personal, Advisory Board: Eli Lilly and Company; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Research Grant, Advisory board, Speaker bureau, travel expense: AstraZeneca; Financial Interests, Personal, Advisory Board: EirGenix; Financial Interests, Research Grant: MSD; Financial Interests, Personal, Invited Speaker, Advisory board, speaker bureau: Novartis; Financial Interests, Research Grant: Daiichi Sankyo; Financial Interests, Research Grant: OBI Pharma; Financial Interests, Personal, Research Grant, advisory board, speaker bureau, travel expense: Pfizer; Financial Interests, Personal, Research Grant, advisory board, speaker bureau, travel expense: Roche. R.J. Wei, S.C. Nabinger, T. Forrester: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. N. Harbeck: Financial Interests, Personal, Other, Lectures, Consulting: Pfizer; Financial Interests, Personal, Other, Lectures, Consulting: AstraZeneca; Financial Interests, Personal, Other, Lectures, Consulting: Eli Lilly and Company; Financial Interests, Personal, Other, Lectures, Consulting: Novartis. All other authors have declared no conflicts of interest.

Background

Neratinib is registered in Europe as extended adjuvant treatment for adult patients with Human Epidermal Growth Factor Receptor 2-positive (HER2+) and Hormone receptor-positive (HR+) eBC within one year after completed adjuvant trastuzumab-based therapy (“EMA-/Swiss-label” population). In the ExteNET trial, extended adjuvant neratinib improved the absolute 5-year invasive disease-free survival rate by 5.1% vs. placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]). More pronounced benefit was observed in patients with non-pCR after neoadjuvant trastuzumab-based therapy and/or in patients who completed one year of neratinib (descriptive post-hoc analyses). In the absence of primary prophylaxis, grade 3 diarrhea occurred in 39% of patients in the ExteNET trial. ELEANOR is the first study to investigate real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland.

Methods

300 patients with HER2+/HR+ eBC will be enrolled in accordance with the specifications of the local Summary of Product Characteristics. Primary objective is the proportion of patients adherent to neratinib treatment (i.e., neratinib intake for ≥75% of treatment days). Secondary objectives include analysis of prior trastuzumab-based therapies (including pertuzumab and T-DM1), neratinib dosing and management, relapses, safety / tolerability, and health-related quality of life (using the CANKADO eHealth application).

Results

Between July 2020 and Feb 2022, 206 patients were enrolled at 59 sites; patient enrollment is ongoing. We will present results from the interim analysis on the first 150 enrolled patients who have been observed for at least 3 months (data cut Nov 2021, analyses ongoing). Baseline demographics and tumor characteristics, prior trastuzumab-based treatments, and neratinib safety and tolerability will be reported.

Conclusions

ELEANOR will help to characterize adherence to neratinib and use of extended adjuvant HER2-targeted therapy in the current treatment landscape focusing on neratinib management after different prior therapies.

Editorial acknowledgement

Editorial assistance was provided by Anna Resch, Pierre Fabre Pharma GmbH, Freiburg, Germany.

Legal entity responsible for the study

Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).

Funding

Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).

Disclosure

N. Harbeck: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Eli Lilly, Gilead, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen, WSG; Financial Interests, Institutional, Other: clinical trials. D. Wrobel: Financial Interests, Personal, Other: Roche, Novartis. M. Zaiss: Financial Interests, Personal, Other: Celgene, AstraZeneca, RG, AKS, Vifor, Pfizer, Janssen, Novartis, AbbVie; Financial Interests, Personal and Institutional, Other: Roche, Eli Lilly; Financial Interests, Institutional, Other: GBG. R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. U. Breitenstein: Financial Interests, Institutional, Other: Novartis, Roche, AstraZeneca, Eli Lilly, Pierre Fabre, Pfizer, SAKK; Non-Financial Interests, Personal, Other: SGMO, SGS, SAKK. M. Schwitter: Financial Interests, Personal and Institutional, Other: Pierre Fabre. M. Balic: Financial Interests, Personal, Other: Amgen, Pierre Fabre, Daiichi Sankyo, Bayer, Samsung, Seagen; Financial Interests, Personal and Institutional, Other: Novartis, Eli Lilly, Pfizer, Celgene, AstraZeneca, MSD, Roche; Financial Interests, Institutional, Other: ABCSG, IBCSG, BIG. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Eisai, Pfizer, Eli Lilly, Novartis, Exact Sciences; Non-Financial Interests, Personal, Other: Roche. V. Müller: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead; Financial Interests, Institutional, Other: Novartis, Roche, Seattle Genetics, Genentech. G. Rinnerthaler: Financial Interests, Personal and Institutional, Other: Roche, Pierre Fabre; Financial Interests, Personal, Other: AstraZeneca, Novartis, BMS, Roche, Pfizer, Eli Lilly, MSD, Daiichi Sankyo. M. Schmidt: Financial Interests, Personal, Other: Amgen, Seagen; Financial Interests, Personal and Institutional, Other: Pierre Fabre, Roche, Pfizer, Novartis, AstraZeneca, Eisai, Pantarhei, BioNTech; Financial Interests, Institutional, Other: Genentech; Non-Financial Interests, Personal, Other: Roche, Pfizer, Pantarhei, BioNTech; Non-Financial Interests, Personal, Other, Issued patent EP: 2951317, Issued patent EP: 2390370: Other. K. Zaman: Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Institutional, Other: Eli Lilly, Novartis, MSD Oncology, Mylan, Daiichi Sankyo, Pierre Fabre, Genentech. T. Schinköthe: Financial Interests, Personal, Full or part-time Employment: CANKADO Service GmbH; Financial Interests, Personal, Ownership Interest: CANKADO Service GmbH. D. Lüftner: Financial Interests, Institutional, Other: Novartis; Financial Interests, Personal, Other: Amgen, Pfizer, GSK, Loreal, Teva, Gilead, Sanofi Aventis, Daiichi Sankyo, Samsung, AstraZeneca, Novartis. All other authors have declared no conflicts of interest.

Background

Gaps in RW evidence exist regarding pts’ and health-care professionals’ (HCPs) perspectives on SEs impacting QOL. Previously, RW survey results showed disconnects between pts with ABC and HCPs on the importance of QOL discussions (Cardoso, SABCS 2021). Here, we examine how SEs impacting QOL in pts with ABC are perceived.

Methods

The survey was designed by a committee of oncologists, nurses, advocates, and pts. After ethical approval, data were collected from July 2020 to May 2021 via a cross-sectional online survey of oncologists, nurses, and pts with HR+/HER2− ABC in 7 countries. HCPs and pts were surveyed on the impact of SEs on QOL and HCP interactions. Observations were assessed using a 4-point Likert scale.

Results

The survey was completed by 467 pts and 502 HCPs. Most pts and HCPs believed fear of progression (76% & 92%, respectively) and pain (73% & 96%) had a moderate/severe impact on QOL. The most common SEs experienced by pts since starting ABC tx or their current tx were fatigue (73% & 64%) and pain (64% & 42% [back pain]). Fatigue relieved by rest was believed to have a moderate/severe impact on QOL more so by pts (78%) than HCPs (40%). Most pts did not discuss SEs with HCPs (79% for fatigue, 74% for pain) until these were moderate/severe. Pts reported that insomnia (83%), anxiety (82%), back pain (78%), fatigue (77%), and diarrhea (71%) had a moderate/severe impact on their QOL. Pts were least willing to live with back pain (52%), fatigue (42%), diarrhea (41%), and loss of appetite (41%) even if tx was working. In pts on a CDK4/6i, 83% experienced ≥ 1 moderate/severe SE, with insomnia (85%), diarrhea (75%), back pain (75%), and fatigue (74%) having a moderate/severe impact on QOL.

Conclusions

Pts with ABC and HCPs were generally aligned on SEs that severely impacted QOL, but HCPs may undervalue the impact of mild SEs on pts. Fatigue and pain were the most common SEs experienced by pts. In pts on a CDK4/6i, insomnia, diarrhea, back pain, and fatigue had a moderate/severe impact on QOL. These data support close monitoring, early intervention, and when indicated, prophylaxis of SEs that may greatly impact QOL in pts with ABC.

Editorial acknowledgement

Medical writing support was provided by Shashank Tandon at MediTech Media, funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

F. Cardoso: Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Astellas/Medivation; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: EISAI; Financial Interests, Personal, Other: GE Oncology; Financial Interests, Personal, Other: Genentech; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Macrogenics; Financial Interests, Personal, Other: Medscape; Financial Interests, Personal, Other: Merck-Sharp; Financial Interests, Personal, Other: Merus; Financial Interests, Personal, Other: Mylan; Financial Interests, Personal, Other: Mundipharma; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: prIME Oncology; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Sanofi; Financial Interests, Personal, Other: Samsung Bioepis; Financial Interests, Personal, Other: Teva; Financial Interests, Personal, Other: Seagen; Financial Interests, Personal, Other: Debiopharm; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Iqvia; Financial Interests, Personal, Other: Touchime; Other, Personal, Writing Engagements, Medical Writer Support: Novartis. J. Rihani: Financial Interests, Personal, Invited Speaker, For participating in various Novartis (sponsored) events, i.e. giving talks, a member in committees and on patient engagement panels: Novartis. D. Aubel: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. J. de Courcy: Financial Interests, Institutional, Other, Adelphi Real World received payment from Novartis to conduct the study: Novartis; Financial Interests, Institutional, Other, Adelphi Real World received payment from Novartis to conduct the study: Adelphi Real World. N. Harbeck: Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Invited Speaker, Lectures: Lilly; Financial Interests, Personal, Other, Consulting: Lilly; Financial Interests, Personal, Invited Speaker, Lectures: AstraZeneca; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Lectures: MSD; Financial Interests, Personal, Other, Consulting: MSD; Financial Interests, Personal, Invited Speaker, Lectures: Pierre Fabre; Financial Interests, Personal, Other, Consulting: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Lectures: Roche; Financial Interests, Personal, Other, Consulting: Roche; Financial Interests, Personal, Invited Speaker, Lectures: Sandoz/Hexal; Financial Interests, Personal, Other, Consulting: Sandoz/Hexal; Financial Interests, Personal, Invited Speaker, Lectures: Seattle Genetics; Financial Interests, Personal, Other, Consulting: Seattle Genetics; Non-Financial Interests, Personal, Member of the Board of Directors, Co-Director WSG: West German Study Group. H.S. Rugo: Financial Interests, Institutional, Research Grant, Grant - Institution: Plexxikon; Financial Interests, Institutional, Research Grant, Grant - Institution: Macrogenics; Financial Interests, Institutional, Research Grant, Grant - Institution: OBI Pharma; Financial Interests, Institutional, Research Grant, Grant - Institution: Eisai; Financial Interests, Institutional, Research Grant, Grant - Institution: Pfizer; Financial Interests, Institutional, Research Grant, Grant - Institution: Novartis; Financial Interests, Institutional, Research Grant, Grant - Institution: Eli Lilly; Financial Interests, Institutional, Research Grant, Grant - Institution: GlaxoSmithKline; Financial Interests, Institutional, Research Grant, Grant - Institution: Genentech; Financial Interests, Institutional, Research Grant, Grant - Institution: Celsion; Financial Interests, Institutional, Research Grant, Grant - Institution: Merck; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Roche/Genentech; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: OBI Pharma; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Genomic Health. P.A. Fasching: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Funding, Institutional Funding: BioNTech; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Funding, Institutional Funding: Cepheid; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Advisory Board: Gilead.

S. Haftchenary: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares, Stock ownership: Novartis. P. Pathak: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares, Stock ownership: Novartis. All other authors have declared no conflicts of interest.

Background

Abemaciclib is the first and only approved CDK4 & 6 inhibitor in the adjuvant setting for certain types of HR+, HER2-, node-positive, high-risk early breast cancer (EBC). Patient (Pts) with HR+, HER2- tumors who are premenopausal (preM) may have a different tumor biology and response to endocrine therapy (ET) than postmenopausal (postM) pts, warranting analysis of the prespecified subgroup within monarchE.

Methods

Randomized (1:1) pts received adjuvant ET +/- abemaciclib for 2 years (yrs) plus at least 3 yrs of ET as clinically indicated. Menopausal status (preM vs. postM) at diagnosis was a predefined stratification factor. Standard ET (tamoxifen or an aromatase inhibitor), with or without additional GnRH, was determined by physician’s choice. Baseline disease characteristics and ET choice were described at ESMO, 2021. Efficacy and safety results of abemaciclib + ET vs. ET alone including invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) were assessed by menopausal status with a data cut-off date on 1 April 2021, at a median follow-up of 27 months.

Results

Among randomized pts, 2451 (43.5%) were preM and 3181 (56.4%) postM. Treatment benefit was consistent in both menopausal status subgroups, with numerically greater effect size in preM subgroup compared to postM subgroup (Table). For preM pts, abemaciclib + ET resulted in a 42.7% and 40.8% reduction in risk of developing an IDFS and DRFS event, respectively. The absolute improvement at 3 yrs was 5.7% for IDFS and 4.4% for DRFS rates. The safety profile for preM pts was consistent with the safety population. Table: 63P

Efficacy data by menopausal status

Conclusions

Abemaciclib + ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS vs. ET alone regardless of menopausal status, with a numerically greater benefit in the preM population. Safety data in preM pts is consistent with the overall safety profile of abemaciclib.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Medical writing support was provided by Trish Huynh (Eli Lilly and Company, IN, USA).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

S. Paluch-Shimon: Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Roche; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Pfizer; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Novartis; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Exact sciences; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Eli Lilly; Financial Interests, Institutional, Other, Advisory board, speaker's bureau, consultancy: Medison; Financial Interests, Personal and Institutional, Research Grant, Research grant for an RFP independent research put out by SPCC and Pfizer: SPCC (Shared Progress in Cancer Care). P. Neven: Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Roularta Belgium; Financial Interests, Personal, Other, Lecture fees: Eli Lilly; Financial Interests, Personal, Other, Lecture fees: Novartis; Financial Interests, Personal, Other, Lecture fees: Pfizer; Financial Interests, Personal, Other, Lecture fees: AstraZeneca. J. Huober: Financial Interests, Research Grant: Celgene; Financial Interests, Research Grant: Novartis; Financial Interests, Research Grant: Hexal; Financial Interests, Research Grant: Eli Lilly and Company; Financial Interests, Other, Honoraria: Eli Lilly and Company; Financial Interests, Other, Honoraria: Novartis; Financial Interests, Other, Honoraria: Roche; Financial Interests, Other, Honoraria: Pfizer; Financial Interests, Other, Honoraria: AstraZeneca; Financial Interests, Other, Honoraria: MSD; Financial Interests, Other, Honoraria: Celgene; Financial Interests, Other, Honoraria: Eisai; Financial Interests, Other, Honoraria: AbbVie; Financial Interests, Other, Honoraria: Seagen; Financial Interests, Other, Honoraria: Gilead; Financial Interests, Advisory Role: Eli Lilly and Company; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Hexal; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: AbbVie; Financial Interests, Advisory Role: Seagen; Financial Interests, Advisory Role: Gilead; Financial Interests, Other, Travel expenses: Roche; Financial Interests, Other, Travel expenses: Pfizer; Financial Interests, Other, Travel expenses: Novartis; Financial Interests, Other, Travel expenses: Celgene; Financial Interests, Other, Travel expenses: Daiichi. Z. Jiang: Financial Interests, Advisory Board: Eli Lilly and Company; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: AbbVie; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Amgen; Financial Interests, Advisory Board: Glaxo Smith Kline; Financial Interests, Advisory Board: Boehringer Ingelheim. M.P. Goetz: Other, Institutional, Other, Consulting: Eagle Pharmaceuticals; Other, Institutional, Other, Consulting: Eli Lilly and Company; Other, Institutional, Other, Consulting: Biovica; Other, Institutional, Other, Consulting: Novartis; Other, Institutional, Other, Consulting: Sermonix; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Research Grant: Eli Lilly and Company; Other, Institutional, Other, Consulting: Pfizer; Other, Institutional, Other, Consulting: Biotheranostics; Financial Interests, Institutional, Research Grant: Sermonix; Other, Institutional, Other, Consulting: AstraZeneca; Other, Institutional, Other, Consulting: Blueprint Medicines; Other, Personal, Other, Consulting: Research to Practice; Other, Personal, Other, Consulting: Clinical Education Alliance. C. Shimizu: Financial Interests, Research Grant: Eli Lilly and Company; Financial Interests, Personal, Invited Speaker, Lecture Fee: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture Fee: Chugai; Financial Interests, Personal, Invited Speaker, Lecture Fee: Taiho; Financial Interests, Personal, Other, Honoraria: AstraZeneca. C. Huang: Financial Interests, Personal, Advisory Board: Eli Lilly and Company; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Research Grant, Advisory board, Speaker bureau, travel expense: AstraZeneca; Financial Interests, Personal, Advisory Board: EirGenix; Financial Interests, Research Grant: MSD; Financial Interests, Personal, Invited Speaker, Advisory board, speaker bureau: Novartis; Financial Interests, Research Grant: Daiichi Sankyo; Financial Interests, Research Grant: OBI Pharma; Financial Interests, Personal, Research Grant, advisory board, speaker bureau, travel expense: Pfizer; Financial Interests, Personal, Research Grant, advisory board, speaker bureau, travel expense: Roche. R.J. Wei, S.C. Nabinger, T. Forrester: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. N. Harbeck: Financial Interests, Personal, Other, Lectures, Consulting: Pfizer; Financial Interests, Personal, Other, Lectures, Consulting: AstraZeneca; Financial Interests, Personal, Other, Lectures, Consulting: Eli Lilly and Company; Financial Interests, Personal, Other, Lectures, Consulting: Novartis. All other authors have declared no conflicts of interest.

Background

Neratinib is registered in Europe as extended adjuvant treatment for adult patients with Human Epidermal Growth Factor Receptor 2-positive (HER2+) and Hormone receptor-positive (HR+) eBC within one year after completed adjuvant trastuzumab-based therapy (“EMA-/Swiss-label” population). In the ExteNET trial, extended adjuvant neratinib improved the absolute 5-year invasive disease-free survival rate by 5.1% vs. placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]). More pronounced benefit was observed in patients with non-pCR after neoadjuvant trastuzumab-based therapy and/or in patients who completed one year of neratinib (descriptive post-hoc analyses). In the absence of primary prophylaxis, grade 3 diarrhea occurred in 39% of patients in the ExteNET trial. ELEANOR is the first study to investigate real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland.

Methods

300 patients with HER2+/HR+ eBC will be enrolled in accordance with the specifications of the local Summary of Product Characteristics. Primary objective is the proportion of patients adherent to neratinib treatment (i.e., neratinib intake for ≥75% of treatment days). Secondary objectives include analysis of prior trastuzumab-based therapies (including pertuzumab and T-DM1), neratinib dosing and management, relapses, safety / tolerability, and health-related quality of life (using the CANKADO eHealth application).

Results

Between July 2020 and Feb 2022, 206 patients were enrolled at 59 sites; patient enrollment is ongoing. We will present results from the interim analysis on the first 150 enrolled patients who have been observed for at least 3 months (data cut Nov 2021, analyses ongoing). Baseline demographics and tumor characteristics, prior trastuzumab-based treatments, and neratinib safety and tolerability will be reported.

Conclusions

ELEANOR will help to characterize adherence to neratinib and use of extended adjuvant HER2-targeted therapy in the current treatment landscape focusing on neratinib management after different prior therapies.

Editorial acknowledgement

Editorial assistance was provided by Anna Resch, Pierre Fabre Pharma GmbH, Freiburg, Germany.

Legal entity responsible for the study

Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).

Funding

Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).

Disclosure

N. Harbeck: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Eli Lilly, Gilead, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen, WSG; Financial Interests, Institutional, Other: clinical trials. D. Wrobel: Financial Interests, Personal, Other: Roche, Novartis. M. Zaiss: Financial Interests, Personal, Other: Celgene, AstraZeneca, RG, AKS, Vifor, Pfizer, Janssen, Novartis, AbbVie; Financial Interests, Personal and Institutional, Other: Roche, Eli Lilly; Financial Interests, Institutional, Other: GBG. R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. U. Breitenstein: Financial Interests, Institutional, Other: Novartis, Roche, AstraZeneca, Eli Lilly, Pierre Fabre, Pfizer, SAKK; Non-Financial Interests, Personal, Other: SGMO, SGS, SAKK. M. Schwitter: Financial Interests, Personal and Institutional, Other: Pierre Fabre. M. Balic: Financial Interests, Personal, Other: Amgen, Pierre Fabre, Daiichi Sankyo, Bayer, Samsung, Seagen; Financial Interests, Personal and Institutional, Other: Novartis, Eli Lilly, Pfizer, Celgene, AstraZeneca, MSD, Roche; Financial Interests, Institutional, Other: ABCSG, IBCSG, BIG. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Eisai, Pfizer, Eli Lilly, Novartis, Exact Sciences; Non-Financial Interests, Personal, Other: Roche. V. Müller: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead; Financial Interests, Institutional, Other: Novartis, Roche, Seattle Genetics, Genentech. G. Rinnerthaler: Financial Interests, Personal and Institutional, Other: Roche, Pierre Fabre; Financial Interests, Personal, Other: AstraZeneca, Novartis, BMS, Roche, Pfizer, Eli Lilly, MSD, Daiichi Sankyo. M. Schmidt: Financial Interests, Personal, Other: Amgen, Seagen; Financial Interests, Personal and Institutional, Other: Pierre Fabre, Roche, Pfizer, Novartis, AstraZeneca, Eisai, Pantarhei, BioNTech; Financial Interests, Institutional, Other: Genentech; Non-Financial Interests, Personal, Other: Roche, Pfizer, Pantarhei, BioNTech; Non-Financial Interests, Personal, Other, Issued patent EP: 2951317, Issued patent EP: 2390370: Other. K. Zaman: Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Institutional, Other: Eli Lilly, Novartis, MSD Oncology, Mylan, Daiichi Sankyo, Pierre Fabre, Genentech. T. Schinköthe: Financial Interests, Personal, Full or part-time Employment: CANKADO Service GmbH; Financial Interests, Personal, Ownership Interest: CANKADO Service GmbH. D. Lüftner: Financial Interests, Institutional, Other: Novartis; Financial Interests, Personal, Other: Amgen, Pfizer, GSK, Loreal, Teva, Gilead, Sanofi Aventis, Daiichi Sankyo, Samsung, AstraZeneca, Novartis. All other authors have declared no conflicts of interest.