N. Chic (Barcelona, Spain)

Hospital Clinic y Provincial de Barcelona

Author Of 5 Presentations

 On-Demand ePoster Display

16P - Understanding the biologic determinants of ribociclib efficacy in breast cancer

Abstract

Background

Ribociclib improves survival in hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer (BC). Deeper understanding of the biology associated with ribociclib efficacy is needed, especially within the HER2-enriched (HER2-E) subtype given recent analysis of MONALEESA program. Here, we performed gene expression (GE) analysis with/without ribociclib monotherapy in BC patient-derived xenografts (PDX).

Methods

Eighteen PDXs representative of HR+/HER2- (n=11, 61%), HER2+ (n=6, 33%) and triple-negative (n=1, 6%) BC were treated with ribociclib monotherapy (75 mg/kg/day). The % change in tumor volume from baseline was calculated at day 35. RNA was obtained from flash-frozen tumors at baseline and day 12. PAM50 GE was analyzed by nCounter and associated with tumor response (as a continuous variable) using quantitative Statistical Analysis Microarrays (SAM). Differential GE during ribociclib treatment was identified using two-class paired SAM. All SAM used a false-discovery rate<5%.

Results

Baseline PAM50 subtype distribution was Luminal B (44%), HER2-E (33%) and Basal-like (B-L) (22%). HER2-E and Luminal B PDXs showed a statistically significant higher response to ribociclib (mean change in volume >40% and >140%), than B-L (>660%). Baseline GE analysis identified 6 genes highly expressed in responders (FOXA1, ERBB2, GRB7, MLPH, GPR160 and CXXC5), and 7 lower expressed genes (SFRP1, KRT17, MYC, CDH3, KRT5, MIA and KRT14). Paired GE analyses across PDXs identified 12 upregulated genes during treatment, including estrogen activation-related genes (ESR1, PGR, FOXA1, MAPT or BLVRA); and 12 downregulated genes, including proliferation-related genes (MKI67 or KIF2C) and HER2-E-related genes (ERBB2 or TMEM45B). Similar results were obtained with HR+/HER2- PDXs when analyzed separately.

Conclusions

In BC PDXs, B-L biology associates with lower response to ribociclib monotherapy than Luminal or HER2-E. Ribociclib induces a luminal phenotype with high GE of estrogen-regulated genes and low GE of proliferation genes, a biological switch that could explain the better efficacy of ribociclib in the endocrine therapy (ET)-resistant HER2-E subtype observed in clinical trials when combined with ET.

Legal entity responsible for the study

Institut d'Investigacions Biomèdiques August Pi i Sunyer.

Funding

Has not received any funding.

Disclosure

M. Oliveira: Honoraria (self): Roche, Novartis, Seattle Genetics; Advisory/Consultancy: Roche/Genentech, GlaxoSmithKline, Puma Biotechnology, AstraZeneca, Seattle Genetics; Research grant/Funding (institution): Philips Healthcare (Inst), Roche/Genentech (Inst), Novartis (Inst), AstraZeneca (Inst), Immunomedics (Inst), Seattle Genetics (Inst), Boehringer Ingelheim (Inst), GlaxoSmithKline (Inst), Cascadian Therapeutics (Inst), Sanofi (Inst), Celldex Therapeutics; Travel/Accommodation/Expenses: Roche, Novartis, Grünenthal Group, Pierre Fabre, GP Pharm, Eisai. N. Chic: Travel/Accommodation/Expenses: Novartis, Eisai, Pierre Fabre. R. Dienstmann: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Research grant/Funding (self): Merck; Research grant/Funding (self): Pierre Fabre. C. Saura Manich: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca, Daiichi Sankyo, Merck, Sharp and Dohme España SA, Novartis, Pfizer, Puma, Synthon; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene, Clovis Oncology, Eisai, F. Hoffmann-La Roche Ltd., Genomic Health, Odonate Therapeutics, Philips Healthwork, Pierre Fabre, prIME Oncology, Sanofi Aventis, Zymeworks; Research grant/Funding (institution): Eli Lilly and Company, Genentech, Immunomedics, Macrogenics, Piqur Therapeutics, Roche, Synthon. A. Prat: Advisory/Consultancy, Research grant/Funding (self): Novartis Farma, SA; Advisory/Consultancy: Lilly Spain; Advisory/Consultancy: Pfizer, SLU; Advisory/Consultancy, Research grant/Funding (self): Roche Farma, SA; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Amgen, SA; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Oncolytics Bioteck; Research grant/Funding (self): Sysmex Europe GmbH; Research grant/Funding (self): Medica Scientia Inno, Research, SL; Research grant/Funding (self): Celgene, SLU; Research grant/Funding (self): Astellas Pharma, SA; Research grant/Funding (self): NanoString Technologies; Officer/Board of Directors, Member executive Board: Breast International Group (BIG).; Officer/Board of Directors, Member executive Board and Foundation: SOLTI; Research grant/Funding (self): Puma; Research grant/Funding (self): Incyte. V. Serra: Research grant/Funding (self): Novartis, Genentech. All other authors have declared no conflicts of interest.

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23P - CDK4/6 inhibition and endocrine therapy (ET) in the HER2-enriched subtype (HER2-E) in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (ABC): a retrospective analysis of real-world data

Abstract

Background

The HER2-E subtype within HR+/HER2- ABC represents 10-25% and is characterized by poor prognosis. In the MONALEESA program, ribociclib + ET was found highly active in this subtype compared to ET. Here, we explored the prognostic and predictive value of HER2-E in patients (pts) treated with a CDK4/6 inhibitor (CDK4/6i) + ET in the real-world setting.

Methods

This is a retrospective study of 144 consecutive pts with HR+/HER2- ABC treated with a CDK4/6i + ET in the first line setting from 2014-2020 in Hospital 12 de Octubre (Madrid) and Clinic of Barcelona. Research-based PAM50 was performed in FFPE tumors collected before CDK4/6i (primary tumors or metastatic biopsies). Univariate and multivariable cox model progression-free survival (PFS) analyses were performed adjusting for the presence of visceral or “de novo” disease, menopausal status and performance status.

Results

114 pts (79%) had PAM50 data (50% primary/50% metastatic), and 47%/46%/7% received palbociclib/ribociclib/abemaciclib. Subtype distribution: Luminal A (33%), Luminal B (37%), HER2-E (19%), normal-like (8%) and Basal-like (5%). Median PFS for HER2-E disease was 7.4 months (mo) (95% confidence interval [CI] 5.0-22.0) and 21.1 mo (95% CI 16.6-31.3) for non-HER2-E disease (adjusted hazard ratio [aHRatio]=2.38, p=0.010). Median OS for HER2-E disease was 30.9 months (mo) (95% confidence interval [CI] 13.2-not reached [NR]) and NR (95% CI 47.2-NR) for non-HER2-E disease (aHRatio=4.39, p=0.021). Although exploratory and statistically non-significant, the PFS HRatio estimates of ribociclib vs palbociclib/abemaciclib in Luminal A, Luminal B and HER2-E subtype were 0.88, 0.90 and 0.44, respectively. Finally, the overall response rate of ribociclib in Luminal A/B and HER2-E disease was 40.5% and 42.9% vs 36.8% and 25.0% with palbociclib/abemaciclib.

Conclusions

In a real-world setting, we confirmed the poor prognosis of the HER2-E subtype in HR+/HER2- ABC. Despite the limitations, our results support the observation from the ML program where ribociclib in combination with ET was particularly active in the HER2-E subtype.

Legal entity responsible for the study

The authors.

Funding

Instituto de Salud Carlos III (PI19/01846) (to A.P.) Instituto 299 de Salud Carlos III (PI18/01408) (to E.C.) Breast Cancer Research Foundation (to 300 A.P.) PhD4MD (to N.C.) Fundació La Marató TV3 (to A.P) RESCUER Horizon 2020 301 (to A.P.) Save the Mama (to A.P.) Pas a Pas (to A.P.) Asociación Cáncer de Mama 302 Metastásico (to A.P.) Fundación Científica Asociación Española Contra el Cáncer (to 303 F.B.M.) Fundación SEOM (SEOM 2018 Grant: Fellowship for Training in 304 Research in Reference Centers) (to T.P.).

Disclosure

O. Martínez-Sáez: Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Eisai. P. Tolosa: Honoraria (institution), Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Eisai. T. Pascual: Advisory/Consultancy: Roche; Advisory/Consultancy: Genentech. N. Chic: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pierre Fabre. J.C. Laguna: Speaker Bureau/Expert testimony: Kyowa Kirin. M. Vidal: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Daiichi Sankyo; Travel/Accommodation/Expenses: Pfizer. M. Muñoz: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Eisai. A. Prat: Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Amgen; Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): MSD Oncology; Advisory/Consultancy: NanoString Technologies; Honoraria (self): Lilly; Advisory/Consultancy: Pfizer. E.M. Ciruelos: Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

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40TiP - SOLTI-1802 ONAWA Trial: A Window of Opportunity Trial of Onapristone (ONA) in Postmenopausal Women with Estrogen and Progesterone Receptor-Positive/HER2-negative (ER+/PgR+/HER2-) Early Breast Cancer (EBC)

Abstract

Background

PgR expression is a biomarker of ER functionality, cellular progression to malignancy, and response to endocrine therapy (ET) in HR+ BC. ONA, a type I antiprogestin showed activity in patients with metastatic BC, but early trials with its immediate release formulation showed liver toxicity and further studies were halted. The development of a new extended-release formulation (Context Therapeutics, PA, USA), which is associated with a lower liver toxicity (Cottu PH, PLOS ONE, 2018) has strongly supported the relaunching of ONA clinical development. ONA blocks Ser294 phosphorylation of PgR, a posttranslational event associated with elevated PgR transcriptional activity coupled to rapid PgR turnover and also, downregulates PgR gene targets both in tumor cells expressing a sumo-deficient/phospho-mimic activated (KR) and non-activated (WT) PgR phenotype, independent to the presence of progesterone. Considering BC heterogeneity and that PgR analysis by standard immunohistochemistry (IHC) does not perfectly correlate with PgR target gene expression, the identification of biomarkers allowing the selection of patients with PgR-driven tumors that may benefit from antiprogestins treatment is currently an unmet need.

Trial design

ONAWA is an open-label, single arm, multicenter window of opportunity clinical trial of ONA (50 mg extended-release tablets BID for 21 days) for postmenopausal women with EBC amenable to receive a short course of ET before surgery. Ten patients with ER+/PgR+/HER2- and ki67 ≥ 15% BC will be enrolled at 4 sites of the SOLTI network. The primary objective is to evaluate the biological activity of ONA by the rate of Complete Cell Cycle Arrest determined by Ki67 (≤2.7%). Secondary endpoints include safety and correlating biological activity with IHC of tumor expression (ER, PgR, Ser294-PgR, CD24, CD44, ALDH1, Ki67), estradiol, and progesterone blood levels, and gene expression profile (NanoString nCounter® Breast 360TM panel). The study was approved in July 2020 and recruitment started in November 2020. Seven patients have been enrolled at the time of this submission.

Clinical trial identification

NCT04142892; EudraCT Number: 2019-001433-13.

Legal entity responsible for the study

SOLTI Breast Cancer Research Group.

Funding

Context Therapeutics.

Disclosure

X. González-Farré: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Eisai; Honoraria (self): SOLTI. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self): NanoString; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Puma. C. Saura Manich: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Hoffman-La Roche; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Genomic Health; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sharp and Dhome España SA; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Philips Healthwork; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: prIME Oncology; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Puma; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Synthon; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi Aventis. All other authors have declared no conflicts of interest.

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109P - Subsequent therapies after progressing to CDK4/6 inhibition (CDK4/6i) in hormone receptor positive/HER2 negative (HR+/HER2-) advanced breast cancer (ABC)

Abstract

Background

There is limited data in the real world setting regarding the effectiveness of subsequent lines of treatment after progressing to CDK4/6i. The optimal therapeutic sequence is still unknown and predictors are needed.

Methods

This is a retrospective single-center study of 99 consecutive patients (pts) with HR+/HER2- ABC who progressed to CDK4/6i + endocrine therapy (ET) in the 1st or 2nd line setting between 05/2015-01/2021. Research-based PAM50 subtyping using the nCounter platform was performed in tumor samples collected before CDK4/6i. Median progression free survival (mPFS) and overall survival (mOS) were calculated using the Kaplan Meier method.

Results

mPFS with CDK4/6i in 1st line (59%) was 10.4 months (m) and 11.7m in 2nd line (41%). At the time of the analysis, 71% of patients had progressed to the subsequent line. mPFS and mOS after CDK4/6i were 5.3 and 19.6m, respectively. No correlation was observed between previous PFS on CDK4/6i and mPFS (p=0.74). mPFS with chemotherapy (CT) (45%) was 6.4m; with ET alone (18%), 2.9m; with ET + everolimus (eve) (10%), 5.1m; with PIK3CA inhibitors + ET (9%), 5.4m; and with other CDK4/6i + ET (3%), 9.1m. Fourteen percent of pts did not receive any subsequent treatment. Responses were only observed with CT (12/44), eve + ET (1/10) and CDK4/6i re-treatment (2/3). PAM50 data was available for 75 pts (75%). Luminal A (30%) showed a mPFS of 6.4m and mOS was not reached; Luminal B (33%), 7.6 and 42.1m; HER2-enriched (19%), 1.8 and 11.6m; Basal-like (10%), 7.9 and 11.5m. Luminal vs. non-luminal disease with ET had a mPFS of 2.9 and 3.7m (p=0.99); with target therapies + ET, 13.8 and 1.7m (p=0.026) and with ET 7.0 and 6.1m (p=0.094). Pts who showed progression to CDK4/6i as the best response (n=19) had a mPFS of 1.7m when treated with ET combinations (n=4) and 8.1m with CT (n=15).

Conclusions

Our exploratory results show limited benefit with post-CDK4/6i therapies, independently from previous PFS. PAM50 subtype remains prognostic in this context. Primary CDK4/6i refractory tumors might benefit more from CT than ET.

Legal entity responsible for the study

Hospital Clinic y Provincial of Barcelona.

Funding

Instituto de Salud Carlos III (PI19/01846) (to A.P.) Breast Cancer Research Foundation (to 300 A.P.) PhD4MD (to N.C.) Fundació La Marató TV3 (to A.P) RESCUER Horizon 2020 301 (to A.P.) Save the Mama (to A.P.) Pas a Pas (to A.P.) Asociación Cáncer de Mama 302 Metastásico (to A.P.) Fundación Científica Asociación Española Contra el Cáncer (to 303 F.B.M.) Fundación SEOM (SEOM 2018 Grant: Fellowship for Training in 304 Research in Reference Centers) (to T.P.).

Disclosure

J.C. Laguna: Speaker Bureau/Expert testimony: Kyowa Kirin. T. Pascual: Advisory/Consultancy: Roche; Advisory/Consultancy: Genentech. N. Chic: Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony: Eisai; Travel/Accommodation/Expenses: Pier Fabre. M. Vidal: Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): Daiichi Sankyo; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis. R. Moreno: Speaker Bureau/Expert testimony: Eisai. A. Prat: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Lilly; Honoraria (self): Daiichi Sankyo; Travel/Accommodation/Expenses: Daiichi Sankyo; Research grant/Funding (self): Roche; Research grant/Funding (self): Novartis; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bristol-Myers Squibb. M. Muñoz: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Eisai; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Eisai; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly. O. Martínez-Sáez: Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Eisai. All other authors have declared no conflicts of interest.

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177P - COVID-19 pandemic impact in newly diagnosed breast cancer patients BCP at a 3rd level hospital

Abstract

Background

On March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. Worldwide, health authorities recommended limiting elective surgeries, diagnostic procedures and non-urgent face-to-face consultations. The full range of consequences of these restrictive measures in cancer diagnosis has not yet been well documented in Spain. Here, we report the impact of these disruptions in the diagnosis of breast cancer at our institution.

Methods

We performed a retrospective study comparing new breast cancer diagnosis at the medical oncology department in a tertiary center in 2019 and 2020. Data corresponding to clinical-pathological features at diagnosis was collected from clinical records. Categorical variables were compared using the Fisher’s exact test and chi-square. Normally-distributed continuous variables were compared using two sample-t-tests. P values of < 0.05 were considered statistically significant.

Results

In 2020, there were 210 new BCP, which represent a 26% decrease compared to 2019 (n=285). The overall number of screening mamograms (SM) decreased from 13041 in 2019 to 8239 in 2020 (37%), resulting in 46% fewer new diagnosis in this group (57 in 2019 vs 31 in 2020). Diagnoses made after referral from other hospital services were also reduced (40 in 2019 vs 23 in 2020, 42% reduction). Smaller reductions were observed in new breast cancer patients referred from other hospitals (19%) and from primary care centers (13%). Diagnoses at stage I, were significantly reduced by 47% (n=135 in 2019 vs n=71 in 2020) and in stage II by 18% (n=108 in 2019 vs n=89 in 2020). Stage III diagnoses were increased by 30% (n=23 in 2019 vs n=30 in 2020) and in stage IV by 11%, although the absolute number of patients was similar in both subgroups (n=18 in 2019 vs n=20 in 2020) (p=0.0068).

Conclusions

Suspension of SM and limited outpatient consultations have contributed to diagnostic delays. Accordingly, higher proportion of patients presented with locally advanced disease. These delays are expected to have an impact in breast cancer specific survival in the coming years. Therefore, our findings should bring awareness about the importance of defining measures to prevent COVID pandemic impact on other diseases.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Vidal: Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Daiichi Sankyo. N. Chic: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pierre Fabre. O. Martínez-Sáez: Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. R. Moreno: Speaker Bureau/Expert testimony: Eisai. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): MSD Oncology; Honoraria (self): Lilly; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Meyers Squib. M. Muñoz: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Eisai; Travel/Accommodation/Expenses: Lilly. All other authors have declared no conflicts of interest.

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