- Email: [email protected]
mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
abstracts
Annals of Oncology Conclusions: accRCC molecular subtypes exhibit different miRNA expression patterns. Differentially expressed miRNAs are implicated in pathways driving tumor biology and strongly correlated with OS. These findings underscore the robustness of the molecular subtypes and are, to the best of our knowledge, the first to show an association of global miRNome expression with outcome. Legal entity responsible for the study: The authors. Funding: Fonds Wetenschappelijk Onderzoek Vlaanderen. Disclosure: M. Albersen: Research grant / Funding (self): Ipsen. B. Beuselinck: Advisory / Consultancy, Research grant / Funding (self): Bristol Meyers Squibb; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (self): Pfizer. All other authors have declared no conflicts of interest.
Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
V. Iebba1, L. Albiges2, L. Alla3, E. Colomba4, C. Alves Costa Silva4, N. Pons3, G. Baciarello4, E. Le Chatelier3, K. Fizazi5, B. Routy6, B. Escudier2, L. Zitvogel7, L. Derosa1 1 U1015, Institut Gustave Roussy, Villejuif, France, 2Medical Oncology, Institut Gustave Roussy, Villejuif, France, 3MGP MetaGe´noPolis, Centre de Recherche, INRA French National, Jouy-en-Josas, France, 4Medical Oncology, Institut Gustave Roussy, Villejuif, France, 5Institut Gustave Roussy, University of Paris Sud, Villejuif, France, 6CHUM, University of Montreal Research Centre, Montreal, QC, Canada, 7U1015, Institut Gustave Roussy, Villejuif, France Background: Evidence suggests that ATB and gut microbiota composition are associated to anti-PD-1 outcomes in RCC patients. Network analysis of the gut microbiota represents a novel tool to determine “guilds” of bacterial communities. Methods: Here, we investigated guilds’ relationships with prior exposure to ATB, TKI [axitinib (axi), sunitinib (suni) or other] and clinical outcomes of RCC patients treated with nivolumab (nivo). Results: Considering prior exposure to ATB (n ¼ 11, 22%), axi (n ¼ 13, 19%), suni (n ¼ 49, 71%) or other TKI (n ¼ 20, 29%), n ¼ 36 (52%) patients were NR and 33 (48%) R to nivo. Cross-validation of overall fecal microbiota composition stratified RCC patients with different predictive power (ATB¼84%; axi¼81%; suni¼69%; outcome¼49%). Network analysis revealed six guilds (G1 to G6). G1-G2 behaved in an opposite way and topologically separated by negative correlations. G1-G2 were both related to NR, while G1 was dominated by species related to ATB. Conversely G2 was mainly represented by species related to no ATB (X2¼8.98, P ¼ 0.0027) and more susceptible to prior TKI exposure (where axi and suni behaved in an opposite way) compared to the other guilds (X2¼10.68, P ¼ 0.0011). G4 was mainly inhabited by species related to other TKI (no axi and no suni). Random forest analysis found definite bacterial species able to drive the stratification into guilds of the global RCC network, such as Akkermansia muciniphila for R and Dorea formicigenerans for no ATB. Conclusions: We show that ATB and suni are the most powerful external features able to drive fecal microbiota compositional shifts in RCC patients treated with nivo. Analysis of the gut microbiota using bacterial communities guilds provides a novel theranostic approach to stratify RCC patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: L. Albiges: Honoraria (self): Novartis, BMS, Amgen, Ipsen, Roche, Pfizer, Astellas, Merck. K. Fizazi: Advisory / Consultancy: Participation to advisory boards/honorarium for: Astellas, AAA, Bayer, Clovis, Curevac, Incyte, Janssen, MSD, Orion, Sanofi. B. Escudier: Advisory / Consultancy: IPSEN, BMS, AZ, Novartis, Roche, Oncorena. L. Zitvogel: Advisory / Consultancy: BMS, AstraZeneca,; Research grant / Funding (self): Incyte, GSK, Transgene, Innovate Biopharma, Pilege; Advisory / Consultancy: Everimmune. All other authors have declared no conflicts of interest.
975P
mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
C. Suarez Rodriguez1, J.A. Arranz Arija2, R. Morales Barrera3, J. Puente4, O. Reig5, L. Faez6, A. Gonzalez del Alba7, B. P. Valderrama8, E. Gallardo9, B. Mellado10, E. Esteban6, J. Jimenez3, A. Vivancos11, J. Carles3 1 Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, 2Oncology, Hospital General Universitario Gregorio Mara~ non, Madrid, Spain, 3Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain, 4Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid, Spain, 5Medical Oncology Department, Hospital Clınic Barcelona, Barcelona, Spain, 6Medical Oncology Department, Hospital Universiatrio Central Asturias, Oviedo, Spain, 7Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, 8Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain, 9Medical Oncology Department, Hospital Parc Taulı, Sabadell, Spain, 10Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, Barcelona, Spain, 11Genomics, Vall d’Hebron University Hospital, Barcelona, Spain Background: Activation of the mTOR pathway is associated with shorter overall survival (OS) in patients (p) with metastatic renal cell carcinoma (mRCC). This outcome could be reversed with mTOR inhibitors (mTORi).
Volume 30 | Supplement 5 | October 2019
Table: 975P Adjusted HR (Cox)
PFS
OS1
OS 2
M/NoM 95% CI p
1.12 0.67 – 1.89 0.660
1.02 0.61 – 1.69 0.946
1.18 0.63 – 2.21 0.607
Conclusions: In a multivariate adjusted model in patients with mRCC treated with mTORi, we did not find the expected worse prognosis associated with mTOR mutations. This finding can be considered as an indirect signal of the effect of mTORi on PFS and OS in patients with mTOR mutations. Although, not the most effective treatment in the overall population, some patients with specific alterations in the mTOR pathway should be considered for an mTORi. Legal entity responsible for the study: Vall dHebron Institute of Oncology. Funding: Has not received any funding. Disclosure: C. Suarez Rodriguez: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy: Eusa; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Sanofi-Aventis; Research grant / Funding (institution), Travel / Accommodation / Expenses, Nonremunerated activity/ies: Roche; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution): Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na, S.A; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution):, F. Hoffmann-La Roche LTD; Research grant / Funding (institution): Genentech INC; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Janssen-Cilag International NV; Research grant / Funding (institution): Karyopharm Therapeutics INC; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly, S.A; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA. J.A. Arranz Arija: Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Pierre-Fabre; Research grant / Funding (institution): Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: Janssen-Cilag. R. Morales Barrera: Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals, INC; Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas Pharma.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na, S.A.; Research grant / Funding (institution): Bristol-Myers Squibb International Corporation (BMS); Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis Oncology, INC,; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: F. Hoffmann-La Roche LTD/Genentech,; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Janssen-Cilag International NV; Advisory / Consultancy: Johnson and Johnson; Research grant / Funding (institution): Karyopharm Therapeutics INC.,; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Medimmune, Millennium Pharmaceuticals, INC.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: MSD; Research grant / Funding (institution): Nanobiotix SA,; Research grant / Funding (institution): Novartis Farmace´utica, S.A; Research grant / Funding (institution): Puma Biotechnology; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: SanofiAventis; Research grant / Funding (institution): Pharma LTD; Research grant / Funding (institution): Teva Pharma S.L.U.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Asofarma. J. Puente: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Astellas; Advisory / Consultancy, Travel /
doi:10.1093/annonc/mdz249 | v395
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974P
Methods: We retrospectively analized by amplicon-seq mutations in mTOR, VEGF, and cell cycle pathways in 90 mRCC p who had received mTORi. A multivariate Cox model including sex, age, non-clear or sarcomatoide component, metastatic sites, IMDC subgroup, and line of mTORi was adjusted to isolate the effect of having mTORi mutations on progression-free survival (PFS), death form diagnosis (OS1) and death from mTORi treatment (OS2). Results: We identified 33% of p having mutations in the mTOR pathway: mTOR (17.8%), PIK3CA (5.6%), PTEN (3.3%), TSC1 (5.6%) and TSC2 (4%). No mutations were found in AKT (AKT1, AKT2, AKT3). OS for favorable, intermediate and poor prognosis of the IMDC were 43.7, 22.2 and 8.7 months respectively. As summarized in the table, in the best adjusted model there were no statistically differences in the hazard ratios (HR) of PFS, OS1 or OS2, between patient with and without mutations (M/ NotM). Four long-term responders to mTORi (> 7 years) harboured mutations in one or more genes of this pathway (p53, PTEN and mTOR). Upon progression one patient adquired an LRPB1 mutation.
abstracts
v396 | Genitourinary Tumours, Non-Prostate
976P
Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in advanced renal cell carcinoma (RCC)
A-K.A. Lalani1, Z. Bakouny2, S. Farah3, W. Xie3, R. Flippot2, J.A. Steinharter2, P.V. Nuzzo2, J. Fleischer2, S.K. Pal4, N. Rathi5, A.R. Hansen6, F. Donskov7, S. Dudani8, T. Yuasa9, U. Vaishampayan10, M. Subasri11, J.C. Wells8, N.S. Basappa12, D.Y.C. Heng8, T.K. Choueiri2 1 Department of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada, 2 Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 3Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA, 4Medical Oncology, City of Hope, Duarte, CA, USA, 5Department of Oncology, Huntsman Cancer Institute, Salt Lake City, UT, USA, 6Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 7Department of Oncology, Aarhus University Hospital, Aarhus, Denmark, 8 Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada, 9 Department of Urology, Japanese Foundation for Cancer Research, Tokyo, Japan, 10 Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA, 11Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada, 12 Medical Oncology, University of Alberta Cross Cancer Institute, Edmonton, AB, Canada Background: An elevated BMI is associated with improved prognosis in certain solid tumors treated with ICI; however, real-world data and genomic analysis has been lacking. We investigated the effect of BMI on RCC patients treated with PD-1/PD-L1 based ICI and explored potential genomic alterations (GA). Methods: Using the International Metastatic RCC Database Consortium (IMDC) database, we performed a retrospective analysis on patients treated with ICI alone or in combination with other therapies. The association of BMI with overall survival (OS), time to treatment failure (TTF), and objective response rate (ORR) was evaluated using Cox and logistic regressions respectively, adjusted for IMDC risk groups, histology, line and type of therapy, age, gender, and race. In an exploratory analysis of patients with clear cell RCC and available NGS panel data (275-447 genes), GA frequencies and tumor mutational burden (TMB) were compared by BMI status using Fisher’s exact and Mann-Whitney U tests. Results were considered statistically significant if p < 0.05 or q < 0.10. Results: Of 1055 eligible patients, 735 had BMI data at start of ICI. Median follow up was 13.5 (<1-78.6) months (mos). Patients were mostly male (76%), had clear cell histology (85%), and were intermediate risk (60%). Overall, 31% received first-line ICI and 31% received combination ICI (19% with VEGF, 12% with CTLA-4/other therapies). At ICI initiation, 274 (37%) patients were considered low BMI (<25 kg/m2) and 461 (63%) considered high BMI (25 kg/m2). Patients with high BMI had better OS compared to those with low BMI, with 1-yr OS 79% vs 66% (adjusted HR ¼ 0.75, 0.570.97, p ¼ 0.03). ORR (30% vs 21%, adjusted p ¼ 0.06) and TTF (median 7.4 vs 4.9 mos, adjusted p ¼ 0.8) did not statistically differ. In a subset of 319 patients with clear cell RCC and available NGS data, GA and TMB (6.81 vs 6.81 mut/Mb, p ¼ 0.9) were found to be similar between those with high BMI compared to low BMI. Conclusions: High BMI is associated with improved OS in advanced RCC patients treated with ICI. In an exploratory analysis, there were no differences in genomic alterations on NGS by BMI status. Further correlative work is ongoing. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S.K. Pal: Advisory / Consultancy: Astellas; Advisory / Consultancy: Aveo; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Myriad; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Medivation. A.R. Hansen: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Pfizer. F. Donskov: Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer. T. Yuasa: Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ono; Advisory / Consultancy: Pfizer. U. Vaishampayan: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Sanofi. N.S. Basappa: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche. D.Y.C. Heng: Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Janssen. T.K. Choueiri: Advisory / Consultancy: Alexion; Advisory / Consultancy: Alligent; Advisory / Consultancy: Analysis Group; Research grant / Funding (institution): Agensys; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Cerulean; Advisory / Consultancy, Research grant / Funding (institution): Corvus; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Peloton; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Prometheus; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz249.071/5576919 by guest on 24 October 2019
Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Clovis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eusa; Advisory / Consultancy: Sanofi-Aventis; Speaker Bureau / Expert testimony: Pierre-Fabre; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony: Kiowa; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Lilly. O. Reig: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Pfizer. L. Faez: Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Pfizer. A. Gonzalez del Alba: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eusa; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: MSD. B. P. Valderrama: Honoraria (self), Advisory / Consultancy: Pierre-Fabre; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi-Aventis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: Janssen-Cilag; Travel / Accommodation / Expenses: Pfizer. E. Gallardo: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Rovi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Daiichi Sankyo; Advisory / Consultancy: Techdow; Travel / Accommodation / Expenses: Pierre Fabre. B. Mellado: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi-Aventis; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer. E. Esteban: Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. A. Vivancos: Advisory / Consultancy, Research grant / Funding (institution): Sysmex; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Guardan Health; Licensing / Royalties: Ferrer; Research grant / Funding (institution): Debio; Research grant / Funding (institution): Cellestia Biotech; Honoraria (institution): Chittern. J. Carles: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Johnson & Johnson; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): SanofiAventis; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): AB Science,; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na, S.A; Research grant / Funding (institution): Clovis Oncology; Speaker Bureau / Expert testimony: Asofarma; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution): Genentech INC; Research grant / Funding (institution): GlaxoSmithKline, SA; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly, S.A; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): SFJ Pharma; Research grant / Funding (institution): Teva Pharma. All other authors have declared no conflicts of interest.
Annals of Oncology
Annals of Oncology Conclusions: accRCC molecular subtypes exhibit different miRNA expression patterns. Differentially expressed miRNAs are implicated in pathways driving tumor biology and strongly correlated with OS. These findings underscore the robustness of the molecular subtypes and are, to the best of our knowledge, the first to show an association of global miRNome expression with outcome. Legal entity responsible for the study: The authors. Funding: Fonds Wetenschappelijk Onderzoek Vlaanderen. Disclosure: M. Albersen: Research grant / Funding (self): Ipsen. B. Beuselinck: Advisory / Consultancy, Research grant / Funding (self): Bristol Meyers Squibb; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (self): Pfizer. All other authors have declared no conflicts of interest.
Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
V. Iebba1, L. Albiges2, L. Alla3, E. Colomba4, C. Alves Costa Silva4, N. Pons3, G. Baciarello4, E. Le Chatelier3, K. Fizazi5, B. Routy6, B. Escudier2, L. Zitvogel7, L. Derosa1 1 U1015, Institut Gustave Roussy, Villejuif, France, 2Medical Oncology, Institut Gustave Roussy, Villejuif, France, 3MGP MetaGe´noPolis, Centre de Recherche, INRA French National, Jouy-en-Josas, France, 4Medical Oncology, Institut Gustave Roussy, Villejuif, France, 5Institut Gustave Roussy, University of Paris Sud, Villejuif, France, 6CHUM, University of Montreal Research Centre, Montreal, QC, Canada, 7U1015, Institut Gustave Roussy, Villejuif, France Background: Evidence suggests that ATB and gut microbiota composition are associated to anti-PD-1 outcomes in RCC patients. Network analysis of the gut microbiota represents a novel tool to determine “guilds” of bacterial communities. Methods: Here, we investigated guilds’ relationships with prior exposure to ATB, TKI [axitinib (axi), sunitinib (suni) or other] and clinical outcomes of RCC patients treated with nivolumab (nivo). Results: Considering prior exposure to ATB (n ¼ 11, 22%), axi (n ¼ 13, 19%), suni (n ¼ 49, 71%) or other TKI (n ¼ 20, 29%), n ¼ 36 (52%) patients were NR and 33 (48%) R to nivo. Cross-validation of overall fecal microbiota composition stratified RCC patients with different predictive power (ATB¼84%; axi¼81%; suni¼69%; outcome¼49%). Network analysis revealed six guilds (G1 to G6). G1-G2 behaved in an opposite way and topologically separated by negative correlations. G1-G2 were both related to NR, while G1 was dominated by species related to ATB. Conversely G2 was mainly represented by species related to no ATB (X2¼8.98, P ¼ 0.0027) and more susceptible to prior TKI exposure (where axi and suni behaved in an opposite way) compared to the other guilds (X2¼10.68, P ¼ 0.0011). G4 was mainly inhabited by species related to other TKI (no axi and no suni). Random forest analysis found definite bacterial species able to drive the stratification into guilds of the global RCC network, such as Akkermansia muciniphila for R and Dorea formicigenerans for no ATB. Conclusions: We show that ATB and suni are the most powerful external features able to drive fecal microbiota compositional shifts in RCC patients treated with nivo. Analysis of the gut microbiota using bacterial communities guilds provides a novel theranostic approach to stratify RCC patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: L. Albiges: Honoraria (self): Novartis, BMS, Amgen, Ipsen, Roche, Pfizer, Astellas, Merck. K. Fizazi: Advisory / Consultancy: Participation to advisory boards/honorarium for: Astellas, AAA, Bayer, Clovis, Curevac, Incyte, Janssen, MSD, Orion, Sanofi. B. Escudier: Advisory / Consultancy: IPSEN, BMS, AZ, Novartis, Roche, Oncorena. L. Zitvogel: Advisory / Consultancy: BMS, AstraZeneca,; Research grant / Funding (self): Incyte, GSK, Transgene, Innovate Biopharma, Pilege; Advisory / Consultancy: Everimmune. All other authors have declared no conflicts of interest.
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mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
C. Suarez Rodriguez1, J.A. Arranz Arija2, R. Morales Barrera3, J. Puente4, O. Reig5, L. Faez6, A. Gonzalez del Alba7, B. P. Valderrama8, E. Gallardo9, B. Mellado10, E. Esteban6, J. Jimenez3, A. Vivancos11, J. Carles3 1 Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, 2Oncology, Hospital General Universitario Gregorio Mara~ non, Madrid, Spain, 3Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain, 4Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid, Spain, 5Medical Oncology Department, Hospital Clınic Barcelona, Barcelona, Spain, 6Medical Oncology Department, Hospital Universiatrio Central Asturias, Oviedo, Spain, 7Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, 8Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain, 9Medical Oncology Department, Hospital Parc Taulı, Sabadell, Spain, 10Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, Barcelona, Spain, 11Genomics, Vall d’Hebron University Hospital, Barcelona, Spain Background: Activation of the mTOR pathway is associated with shorter overall survival (OS) in patients (p) with metastatic renal cell carcinoma (mRCC). This outcome could be reversed with mTOR inhibitors (mTORi).
Volume 30 | Supplement 5 | October 2019
Table: 975P Adjusted HR (Cox)
PFS
OS1
OS 2
M/NoM 95% CI p
1.12 0.67 – 1.89 0.660
1.02 0.61 – 1.69 0.946
1.18 0.63 – 2.21 0.607
Conclusions: In a multivariate adjusted model in patients with mRCC treated with mTORi, we did not find the expected worse prognosis associated with mTOR mutations. This finding can be considered as an indirect signal of the effect of mTORi on PFS and OS in patients with mTOR mutations. Although, not the most effective treatment in the overall population, some patients with specific alterations in the mTOR pathway should be considered for an mTORi. Legal entity responsible for the study: Vall dHebron Institute of Oncology. Funding: Has not received any funding. Disclosure: C. Suarez Rodriguez: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy: Eusa; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Sanofi-Aventis; Research grant / Funding (institution), Travel / Accommodation / Expenses, Nonremunerated activity/ies: Roche; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution): Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na, S.A; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution):, F. Hoffmann-La Roche LTD; Research grant / Funding (institution): Genentech INC; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Janssen-Cilag International NV; Research grant / Funding (institution): Karyopharm Therapeutics INC; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly, S.A; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA. J.A. Arranz Arija: Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Pierre-Fabre; Research grant / Funding (institution): Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: Janssen-Cilag. R. Morales Barrera: Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals, INC; Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas Pharma.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na, S.A.; Research grant / Funding (institution): Bristol-Myers Squibb International Corporation (BMS); Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis Oncology, INC,; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: F. Hoffmann-La Roche LTD/Genentech,; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Janssen-Cilag International NV; Advisory / Consultancy: Johnson and Johnson; Research grant / Funding (institution): Karyopharm Therapeutics INC.,; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Medimmune, Millennium Pharmaceuticals, INC.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: MSD; Research grant / Funding (institution): Nanobiotix SA,; Research grant / Funding (institution): Novartis Farmace´utica, S.A; Research grant / Funding (institution): Puma Biotechnology; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: SanofiAventis; Research grant / Funding (institution): Pharma LTD; Research grant / Funding (institution): Teva Pharma S.L.U.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Asofarma. J. Puente: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Astellas; Advisory / Consultancy, Travel /
doi:10.1093/annonc/mdz249 | v395
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974P
Methods: We retrospectively analized by amplicon-seq mutations in mTOR, VEGF, and cell cycle pathways in 90 mRCC p who had received mTORi. A multivariate Cox model including sex, age, non-clear or sarcomatoide component, metastatic sites, IMDC subgroup, and line of mTORi was adjusted to isolate the effect of having mTORi mutations on progression-free survival (PFS), death form diagnosis (OS1) and death from mTORi treatment (OS2). Results: We identified 33% of p having mutations in the mTOR pathway: mTOR (17.8%), PIK3CA (5.6%), PTEN (3.3%), TSC1 (5.6%) and TSC2 (4%). No mutations were found in AKT (AKT1, AKT2, AKT3). OS for favorable, intermediate and poor prognosis of the IMDC were 43.7, 22.2 and 8.7 months respectively. As summarized in the table, in the best adjusted model there were no statistically differences in the hazard ratios (HR) of PFS, OS1 or OS2, between patient with and without mutations (M/ NotM). Four long-term responders to mTORi (> 7 years) harboured mutations in one or more genes of this pathway (p53, PTEN and mTOR). Upon progression one patient adquired an LRPB1 mutation.
abstracts
v396 | Genitourinary Tumours, Non-Prostate
976P
Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in advanced renal cell carcinoma (RCC)
A-K.A. Lalani1, Z. Bakouny2, S. Farah3, W. Xie3, R. Flippot2, J.A. Steinharter2, P.V. Nuzzo2, J. Fleischer2, S.K. Pal4, N. Rathi5, A.R. Hansen6, F. Donskov7, S. Dudani8, T. Yuasa9, U. Vaishampayan10, M. Subasri11, J.C. Wells8, N.S. Basappa12, D.Y.C. Heng8, T.K. Choueiri2 1 Department of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada, 2 Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 3Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA, 4Medical Oncology, City of Hope, Duarte, CA, USA, 5Department of Oncology, Huntsman Cancer Institute, Salt Lake City, UT, USA, 6Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 7Department of Oncology, Aarhus University Hospital, Aarhus, Denmark, 8 Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada, 9 Department of Urology, Japanese Foundation for Cancer Research, Tokyo, Japan, 10 Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA, 11Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada, 12 Medical Oncology, University of Alberta Cross Cancer Institute, Edmonton, AB, Canada Background: An elevated BMI is associated with improved prognosis in certain solid tumors treated with ICI; however, real-world data and genomic analysis has been lacking. We investigated the effect of BMI on RCC patients treated with PD-1/PD-L1 based ICI and explored potential genomic alterations (GA). Methods: Using the International Metastatic RCC Database Consortium (IMDC) database, we performed a retrospective analysis on patients treated with ICI alone or in combination with other therapies. The association of BMI with overall survival (OS), time to treatment failure (TTF), and objective response rate (ORR) was evaluated using Cox and logistic regressions respectively, adjusted for IMDC risk groups, histology, line and type of therapy, age, gender, and race. In an exploratory analysis of patients with clear cell RCC and available NGS panel data (275-447 genes), GA frequencies and tumor mutational burden (TMB) were compared by BMI status using Fisher’s exact and Mann-Whitney U tests. Results were considered statistically significant if p < 0.05 or q < 0.10. Results: Of 1055 eligible patients, 735 had BMI data at start of ICI. Median follow up was 13.5 (<1-78.6) months (mos). Patients were mostly male (76%), had clear cell histology (85%), and were intermediate risk (60%). Overall, 31% received first-line ICI and 31% received combination ICI (19% with VEGF, 12% with CTLA-4/other therapies). At ICI initiation, 274 (37%) patients were considered low BMI (<25 kg/m2) and 461 (63%) considered high BMI (25 kg/m2). Patients with high BMI had better OS compared to those with low BMI, with 1-yr OS 79% vs 66% (adjusted HR ¼ 0.75, 0.570.97, p ¼ 0.03). ORR (30% vs 21%, adjusted p ¼ 0.06) and TTF (median 7.4 vs 4.9 mos, adjusted p ¼ 0.8) did not statistically differ. In a subset of 319 patients with clear cell RCC and available NGS data, GA and TMB (6.81 vs 6.81 mut/Mb, p ¼ 0.9) were found to be similar between those with high BMI compared to low BMI. Conclusions: High BMI is associated with improved OS in advanced RCC patients treated with ICI. In an exploratory analysis, there were no differences in genomic alterations on NGS by BMI status. Further correlative work is ongoing. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S.K. Pal: Advisory / Consultancy: Astellas; Advisory / Consultancy: Aveo; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Myriad; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Medivation. A.R. Hansen: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Pfizer. F. Donskov: Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer. T. Yuasa: Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ono; Advisory / Consultancy: Pfizer. U. Vaishampayan: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Sanofi. N.S. Basappa: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche. D.Y.C. Heng: Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Janssen. T.K. Choueiri: Advisory / Consultancy: Alexion; Advisory / Consultancy: Alligent; Advisory / Consultancy: Analysis Group; Research grant / Funding (institution): Agensys; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Cerulean; Advisory / Consultancy, Research grant / Funding (institution): Corvus; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Peloton; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Prometheus; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz249.071/5576919 by guest on 24 October 2019
Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Clovis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eusa; Advisory / Consultancy: Sanofi-Aventis; Speaker Bureau / Expert testimony: Pierre-Fabre; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony: Kiowa; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Lilly. O. Reig: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Pfizer. L. Faez: Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Pfizer. A. Gonzalez del Alba: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eusa; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: MSD. B. P. Valderrama: Honoraria (self), Advisory / Consultancy: Pierre-Fabre; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi-Aventis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: Janssen-Cilag; Travel / Accommodation / Expenses: Pfizer. E. Gallardo: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Rovi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Daiichi Sankyo; Advisory / Consultancy: Techdow; Travel / Accommodation / Expenses: Pierre Fabre. B. Mellado: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi-Aventis; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer. E. Esteban: Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. A. Vivancos: Advisory / Consultancy, Research grant / Funding (institution): Sysmex; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Guardan Health; Licensing / Royalties: Ferrer; Research grant / Funding (institution): Debio; Research grant / Funding (institution): Cellestia Biotech; Honoraria (institution): Chittern. J. Carles: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Johnson & Johnson; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): SanofiAventis; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): AB Science,; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na, S.A; Research grant / Funding (institution): Clovis Oncology; Speaker Bureau / Expert testimony: Asofarma; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution): Genentech INC; Research grant / Funding (institution): GlaxoSmithKline, SA; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly, S.A; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): SFJ Pharma; Research grant / Funding (institution): Teva Pharma. All other authors have declared no conflicts of interest.
Annals of Oncology