Background

Up to 30% of metastatic breast cancer (BC) patients (pts) develop brain metastases (BM). Prognosis of pts with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities.

Methods

A total of 2889 out of 3234 pts of the BMBC registry were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the survival curve resulting in a cut-off of 15 months. 887 patients were categorized as long-term survivors.

Results

Long-term survivors compared to other pts were younger at BC and BM diagnosis (median 48 vs 54 years and 53 vs 59 years), had more often HER2+ tumors (59.1% vs 36.3%), less frequently luminal-like (29.1% vs 35.7%) or TNBC (11.9% vs 28.1%), showed better ECOG at time of BM diagnosis (ECOG 0-1 76.9% vs 51.0%), higher pCR rate (21.6% vs 13.7%) and lower number of BM (n=1 BM 40.9% vs 25.4%; n=2-3 BM 26.5% vs 26.7%; n≥4 BM 32.6% vs 47.9%) (p<0.001). Long-term survivors had less leptomeningeal metastases (10.4% vs 17.5%) and extracranial metastases (ECM, 73.6% vs 82.5%), and more often asymptomatic BM at time of BM diagnosis (26.5% vs 20.1, p<0.001). Median OS in long-term survivors was 30.9 months (95% CI 28.8-32.6) overall, 33.9 (95% CI 31.5-37.9) in HER2+, 26.9 (95% CI 25.0-30.9) in luminal-like and 26.5 (95% CI 22.7-31.2) in TNBC pts. Factors significantly associated with a categorization of long-term survivors are presented in the table below. Table: 170P

Multivariate logistic regression in long-term vs short-term survivors

Conclusions

Our analysis identified factors associated with long-term survival of BC pts with BM and characterized clinical features of this patient cohort. Pts with better ECOG status, younger age, lower number of BM, less extended visceral metastases are more likely to show a long-term survival and therefore are more eligible for extended local and systemic treatment.

Legal entity responsible for the study

GBG Forschung.

Funding

Partial Funding Daiichi Sankyo Europe.

Disclosure

M. Schmidt: Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Pantarhei; Financial Interests, Personal, Other: BioNTech; Financial Interests, Personal, Other: Genentech; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: MSD. J. Puppe: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Synlab; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Novartis. K. Lübbe: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisei; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche. M. Thill: Financial Interests, Personal, Advisory Board: Sysmex; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: RTI Surgical; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: pfm Medical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Onkowissen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Neodynamics; Financial Interests, Personal, Advisory Board: Norgine; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Gilead Science; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: ClearCut; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Biom‘Up; Financial Interests, Personal, Advisory Board: Becton/Dickinson; Financial Interests, Personal, Advisory Board: Aurikamed; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Funding: Endomag; Financial Interests, Personal, Funding: Exact Sciences; Financial Interests, Personal, Invited Speaker: Viatris; Financial Interests, Personal, Invited Speaker: Vifor; Financial Interests, Personal, Invited Speaker: Sysmex; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: RTI Surgical; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: pfm Medical; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Omniamed; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Medtronic; Financial Interests, Personal, Invited Speaker: MCI; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Jörg Eickeler; Financial Interests, Personal, Invited Speaker: I-Med-Institute; Financial Interests, Personal, Invited Speaker: Hexal; Financial Interests, Personal, Invited Speaker: Gilead Science; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Connect Medica; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Art Tempi; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other: Clear Cut. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Molecular Health; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Ownership Interest, Cofounder and shareholder of Sividon Diagnostics until 2016: Sividon Diagnostic; Financial Interests, Personal, Invited Speaker: VmScope digital pathology software; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Research Grant: Myriad. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: AbbVie; Financial Interests, Institutional, Advisory Board, Member: Amgen; Financial Interests, Institutional, Advisory Board, Member: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board, Member: Bayer; Financial Interests, Institutional, Advisory Board, Member: BMS; Financial Interests, Institutional, Advisory Board, Member: Celgene; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Advisory Board: DSI; Financial Interests, Institutional, Invited Speaker: DSI; Financial Interests, Institutional, Advisory Board, Member: EirGenix; Financial Interests, Institutional, Advisory Board, Member: GSK; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Advisory Board, Member: Lilly; Financial Interests, Institutional, Advisory Board: Merck KG; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board, Member: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board, Member: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: prIME/Medscape; Financial Interests, Institutional, Advisory Board, Member: prIME/Medscape; Financial Interests, Institutional, Advisory Board, Member: Puma; Financial Interests, Institutional, Advisory Board, Member: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Samsung; Financial Interests, Institutional, Advisory Board, Member: Seagen; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Funding: Cepheid; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Invited Speaker, Executive Board: BIG; Non-Financial Interests, Other, Medical Writing: Amgen; Non-Financial Interests, Other, Medical Writing: AstraZeneca; Non-Financial Interests, Other, Medical Writing: BMS; Non-Financial Interests, Other, Medical Writing: Celgene; Non-Financial Interests, Other, Medical Writing: Daiichi Sankyo; Non-Financial Interests, Other, Medical Writing: Novartis; Non-Financial Interests, Other, Medical Writing: Pfizer; Non-Financial Interests, Other, Medical Writing: Roche; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Chair ESMO Breast; SC: ESMO; Other, EP18209672.7No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent. V. Müller: Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: Teva; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: ClinSol; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Hexal; Financial Interests, Personal, Other: Genomic Health; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis. I. Witzel: Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.

Background

LUCY interim findings confirmed the clinical effectiveness of olaparib 300 mg twice daily in patients with metastatic breast cancer (mBC) in a real world setting. Findings were consistent with the OlympiAD trial of olaparib vs chemotherapy of physician’s choice. We report results of the final planned analysis.

Methods

Eligible adults had germline (g) or somatic (s) BRCA1- and/or BRCA2-mutated (BRCAm), HER2-negative mBC and had received taxane and/or anthracycline in early or metastatic settings and ≤2 previous lines of chemotherapy for mBC. Pts with hormone receptor-positive (HR+) mBC had previously completed ≥1 line of endocrine therapy (ET) in any setting or were unsuitable for further ET. Primary endpoint: investigator-assessed progression-free survival (PFS; gBRCAm cohort). Overall survival (OS) and safety were secondary endpoints. Final analysis was planned at 130 OS events (gBRCAm). Results are in all pts (gBRCAm and sBRCAm). Prespecified subgroups (gBRCAm only): HR status (HR+ vs triple-negative breast cancer [TNBC]); line of therapy (1st line vs 2nd line+).

Results

During 2018, 255 pts were enrolled (252 gBRCAm, 3 sBRCAm; median [m] age: 45.0 [range 22–75] years; 98.4% female). mPFS: 8.2 months (95% CI 7.0–9.2; 208 events, 81.6%). mOS: 24.9 months (95% CI 21.1–27.9; 142 events, 55.7%). OS rate at 30 months: 41.7% (95% CI 35.2–48.1). Treatment-related adverse events (AEs, >10% pts): nausea (47.8%), anaemia (34.5%), asthenia (20.8%), fatigue (18.0%), vomiting (17.6%), neutropenia (15.3%) and diarrhoea (11.0%). Grade ≥3 AEs (17.6% pts) included anaemia (11.8%). Few pts (4.3%) discontinued treatment due to an AE. Post study therapies will be reported.

Conclusions

The benefit of olaparib was similar across HR status and treatment lines. mOS was longer than reported in OlympiAD. No new safety signals were observed. These results strongly support olaparib as a chemotherapy-free alternative for gBRCAm, HER2-negative mBC. Table: 174P

Subgroup analyses (full analysis set)

Editorial acknowledgement

Medical writing assistance was provided by Elizabeth Gandhi, PhD of PharmaGenesis Cambridge, Cambridge, UK, with funding from AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Balmana: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MedSir. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Hecal; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BioNTech; Financial Interests, Institutional, Invited Speaker: Cepheid; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: Arbeitsgemeinschaft für Gynäkologische Onkologie e.V.; Non-Financial Interests, Member: Translational Research in Oncology; Non-Financial Interests, Member: Deutsche Gesellschaft für Senologie e.v. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/Servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Other, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Research Grant: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Other, Research Grant: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Pfizer; Non-Financial Interests, Principal Investigator: Novartis; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Principal Investigator: Lilly; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Principal Investigator: Daiichi Sankyo. J. Sohn: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. S. Aksoy: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck, Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche. C.V. Timcheva: Financial Interests, Personal, Invited Speaker, Presentation during national scientific conference: Roche Bulgaria; Financial Interests, Personal, Advisory Board, Discussion on the place of CDK4/6 inhibitors in the treatment of metastatic breast cancer: Eli Lilly; Financial Interests, Personal, Advisory Board, The role of PARP inhibitors in the treatment of breast and ovarian cancer: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: Parexel; Financial Interests, Personal and Institutional, Invited Speaker, Pi for several clinical trials perforing in the hospital: Roche; Financial Interests, Personal and Institutional, Invited Speaker, PI for some clinical trials performing in the hospital: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, PI for the clinical trial performing in the hospital: I3Research; Non-Financial Interests, Principal Investigator, Investigator initiated trial on metastatic CRC: Merck; Non-Financial Interests, Member, Created in 2012, Head of BAMO until 2020: Bulgarian Association for Medical Oncology (BAMO). T. Park-Simon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pizer; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis. E. John: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca. K. Baria: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G. Walker: Financial Interests, Institutional, Other, I work as a consultant to the company: AstraZeneca. K.A. Gelmon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Ayala; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: BMS. All other authors have declared no conflicts of interest.