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Real world experience of nivolumab therapy in metastatic renal cancer patients: A 3 year multi-centre review
abstracts
Annals of Oncology Conclusions: We report the largest analysis of treatment with N beyond progression in a real world cohort of mRCC supporting that pseudo-progression is a rare event (4%). We show also that treatment beyond progression is very common (49%) and that LDH>200 might be the better ready-to-use predictive factor of a lack of CB. Legal entity responsible for the study: Yann-Alexandre Vano. Funding: Has not received any funding. Disclosure: L. Fournier: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testi-
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First results of safety profile of nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in II and III line of patients (pts) with metastatic renal cell carcinoma (mRCC) in NIVES study
C. Masini1, P. Ciammella2, G. Timon2, R. Gnoni1, U.F.F. De Giorgi3, S.R. Bellia4, S. Buti5, F. Salaroli6, M. Milella7, R. Mazzarotto8, C. Mucciarini9, M.G. Vitale10, A. Bruni11, G. Procopio12, S. Kinspergher13, F. Nole14, F. Morelli15, G. Pappagallo16, C. buttigliero17, C. Pinto18 1 Oncology Unit, Medical Oncology Unit, Clinical Cancer Center, AUSL-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 2Radiation Oncology Unit, Radiation Oncology Unit, AUSL - IRCCS di Reggio Emilia, Italy, Reggio Emilia, Italy, 3Oncology Unit, Istituto Tumori della Romagna I.R.S.T., Meldola, Italy, 4Radiotherapy Unit, Istituto Tumori della Romagna I.R.S.T., Meldola, Italy, 5Medical Oncology Unit, University Hospital of Parma, Parma, Italy, 6Radiotherapy Unit, University Hospital of Parma, Parma, Italy, 7Oncology, Universita degli Studi di Verona, Verona, Italy, 8Radiotherapy Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy, 9Medical Oncology Unit, Ospedale Ramazzini di Capri, Carpi, Italy, 10Department of Hematology and Oncology, Azienda Ospedaliera Universitaria di Modena, Modena, Italy, 11Radiotherapy Unit, Azienda Ospedaliera Universitaria di Modena, Modena, Italy, 12Oncologia Medica, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 13Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy, 14Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy, 15Dipartimento di Onco-Ematologia, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 16 Oncology Department, Unita Locale Socio Sanitaria 13 P.O Mirano, Mirano, Italy, 17 Medical Oncology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy, 18Clinical Cancer Center, Medical Oncology Unit, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy Background: NIVO is an anti-programmed cell death-1 (PD-1) monoclonal antibody; it might work even better when combined with SBRT improving clinical outcomes with a phenomenon known as abscopal effect. To date there are limited data on safety profile of combined SBRT and NIVO in mRCC. We report for the first time the toxicities occurred in phase II NIVES Study. Methods: This is a phase II, single arm, multicentre study in pts with mRCC with progression disease after2 prior anti-angiogenic therapies and with measurable non-brain metastatic sites, at least one of which potentially suitable for SBRT. The pts included received hypofractionated radiation in one lesion at dose of 10 Gy/3 fractions after 7 days from the first infusion of NIVO. NIVO will be given as flat dose of 240 mg on day 1 every 14 days for 6 months, then switch to 480 mg q4-weekly in responding pts until PD or unacceptable toxicity. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed severe Adverse Events (AEs) graded by CTCAE v. 4.03. Results: Sixty-nine pts were enrolled from July 2017 to March 2019 in 11 Italian centers. 79.7% of pts had clear cell histology, median age was 67 years (range 43-85), 82.6% were male. ECOG PS was 0 in 57 pts (82.6%), only 18.8% pts had received 2 previous lines of therapy. The most frequent sites of SBRT were lung (39.4% of pts), lymphonodes (16.7%) and bone (10.6%). Toxicities of grade (G) 3-4 related to NIVO were experienced in 13 pts (18.8%); all G3-4 toxicities were outside of the irradiated area. The most frequently observed G3-4 treatment-related AEs included diarrhea (5.8%), fatigue (4.3%), anemia (2.9%) and increase of amylase/lipase (2.9%). To date no G3-4 pneumonitis were observed. Six pts (8.7%) were hospitalized due to treatment-related SAEs. Overall, 5 of 69 treated pts (7.2%) discontinued therapy because of G3-4 AEs. At the time of this analysis 32/69 pts (46%) are still on treatment. Conclusions: Concurrent NIVO plus SBRT is generally well tolerated, without increased rates of common severe toxicity. Definitive data of toxicities and efficacy of the combination of immunotherapy and radiotherapy are not yet mature. Clinical trial identification: NCT03469713. Legal entity responsible for the study: GOIRC. Funding: GOIRC. Disclosure: C. Masini: Travel / Accommodation / Expenses: BMS, Janssen, Astellas, Bayer; Advisory / Consultancy: Pfizer, Novartis, Sanofi. U.F.F. De Giorgi: Research grant / Funding (institution): AstraZeneca, Roche, Sanofi; Advisory / Consultancy: Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi; Travel / Accommodation / Expenses: BMS, Ipsen, Janssen, Pfizer. S. Buti: Advisory /
Volume 30 | Supplement 5 | October 2019
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Real world experience of nivolumab therapy in metastatic renal cancer patients: A 3 year multi-centre review
J. Hack1, S.L. Hill2, J. Broadfoot3, C. Chau1, T. Geldart3, J. Gale1, K. Fife4, M. Wheater5 Oncology Department, Portsmouth Hospitals NHS Trust, Portsmouth, UK, 2Oncology Department, Southampton General Hospital, Southampton, UK, 3Oncology Department, Royal Bournemouth Hospital, Bournemouth, UK, 4Oncology Department, Cambridge University Hospitals NHS Foundation Trust - Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK, 5Oncology Department, Southampton General Hospital Southampton University Hospitals NHS Trust, Southampton, UK
1
Background: In the UK renal cancer has an incidence of around 12600 cases per year. Nivolumab is an anti-PD1 checkpoint inhibitor, which was approved in the UK for second or subsequent line treatment of advanced renal cancer in 2016. The aim of this study was to evaluate a regional experience of nivolumab use in this setting. Methods: A retrospective analysis was undertaken of patients who commenced nivolumab as monotherapy for advanced renal cancer at three Cancer Centres in South Central England between February 2016 and April 2019. Information was collated from electronic patient records and e-prescribing systems. Information was gathered on patient demographics, Heng (IMDC) prognostic scores, previous treatments, treatment toxicity, use of steroids and radiotherapy during treatment, physician assessment of response and survival data. Results: 109 eligible patients were identified. The average age was 59 with 72.5% of patients male. 67.9% (74/109) of patients had prior nephrectomy and 50.5% (55/109) had metastatic disease at diagnosis. 82.6% (90/109) had pure clear cell histology. 63.3% (69/109) received nivolumab as second-line treatment, 27.5% (30/109) as third-line treatment and 9.2% (10/109) as fourth-line and beyond. At the start of treatment 19.41% (19/103) had a ‘favourable’ risk Heng score, 61.2% (64/103) had an ‘intermediate’ risk and 18.3% (19/103) had a ‘poor’ risk. The number of Nivolumab cycles received ranged from 1-69, with a mean of 11 and median of 5. 45.9% of patients experienced toxicity of any grade, with 16.5% experiencing grade 3/4 toxicity. 24.8% (28/ 109) received radiotherapy and 40.4% (44/109) received steroids during nivolumab treatment. At response assessment 31.5% showed a response to nivolumab, 9.3% had stable disease and 59.3% had disease progression. From the start of nivolumab treatment median progression-free survival was 5.4 months, and the 12-month overall survival rate was 56.88%. 22.6% (24/109) are still receiving nivolumab. Conclusions: This review has given us important real-world data on the safety and efficacy of nivolumab which reflects the findings of the pivotal phase 3 trials that led to it’s use. Further analysis will allow us to see the effect of different factors on these outcomes. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC)
M.T. Campbell1, S. Martin2, A.L. Tam3, R.A. Sheth3, S. Singh4, K. Ahrar3, B. Slack Tidwell5, P. Rao6, J.A. Karam7, C.G. Wood8, N.M. Tannir9, E. Jonasch10, J. Gao11, A.Y. Shah8, J.M. Blando4, F. Duan4, S. Basu4, J. Allison4, P. Sharma12, S. Singh4 1 Genitourinary Medical Oncology, The M. D. Anderson Cancer Center, Houston, TX, USA, 2Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 3 Interventional Radiology, MD Anderson Cancer Center, Houston, TX, USA, 4 Immunology, MD Anderson Cancer Center, Houston, TX, USA, 5Biostatistics, MD Anderson Cancer Center, Houston, TX, USA, 6Pathology Admin, MD Anderson Cancer Center, Houston, TX, USA, 7Urology, MD Anderson Cancer Center, Houston, TX, USA, 8 Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA, 9 Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA, 10GU Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 11Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA, 12Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA Background: Cryo is an effective intervention for palliation and local control for small primary and metastatic tumours in mRCC. Pre-clinical murine tumour modeling found cryo recruits effector immune cells and synergizes with anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) to inhibit tumour rechallenge as compared to either therapy (tx) alone, leading to a prospective pilot study evaluating safety/tolerability.
doi:10.1093/annonc/mdz249 | v389
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz249.058/5576814 by guest on 26 October 2019
mony: Novartis; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Sanofi; Research grant / Funding (institution): Invectys; Research grant / Funding (institution): Philips; Research grant / Funding (institution): Evolucare; Research grant / Funding (institution): ArianaPharma; Research grant / Funding (institution): Imagia. C. Thibault: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. Y. Vano: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Pfizer MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen-Cilag; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Astellas. All other authors have declared no conflicts of interest.
Consultancy: BMS, Pfizer, MSD. M. Milella: Speaker Bureau / Expert testimony: AstraZeneca, Pfizer, EUSA Pharma. M.G. Vitale: Speaker Bureau / Expert testimony: Astellas, Ipsen, Janssen, Pierre Fabre, BMS, Pfizer, Novartis; Travel / Accommodation / Expenses: Astellas, Pfizer, Ipsen, Janssen, BMS, Novartis; Advisory / Consultancy: Janssen, BMS. G. Procopio: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer, BMS, Ipsen, MSD, Novartis, Pfizer. F. Nole: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS, Ipsen, Pfizer, Bayer, Novartis, MSD. G. Pappagallo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen, BMS, Astellas, Janssen, Bayer, Pfizer, Novartis. C. Pinto: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche, BMS, MSD, Janssen, Pfizer, Novartis, Ipsen, Lilly, Bayer. All other authors have declared no conflicts of interest.
Annals of Oncology Conclusions: We report the largest analysis of treatment with N beyond progression in a real world cohort of mRCC supporting that pseudo-progression is a rare event (4%). We show also that treatment beyond progression is very common (49%) and that LDH>200 might be the better ready-to-use predictive factor of a lack of CB. Legal entity responsible for the study: Yann-Alexandre Vano. Funding: Has not received any funding. Disclosure: L. Fournier: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testi-
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First results of safety profile of nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in II and III line of patients (pts) with metastatic renal cell carcinoma (mRCC) in NIVES study
C. Masini1, P. Ciammella2, G. Timon2, R. Gnoni1, U.F.F. De Giorgi3, S.R. Bellia4, S. Buti5, F. Salaroli6, M. Milella7, R. Mazzarotto8, C. Mucciarini9, M.G. Vitale10, A. Bruni11, G. Procopio12, S. Kinspergher13, F. Nole14, F. Morelli15, G. Pappagallo16, C. buttigliero17, C. Pinto18 1 Oncology Unit, Medical Oncology Unit, Clinical Cancer Center, AUSL-IRCCS, Reggio Emilia, Italy, Reggio Emilia, Italy, 2Radiation Oncology Unit, Radiation Oncology Unit, AUSL - IRCCS di Reggio Emilia, Italy, Reggio Emilia, Italy, 3Oncology Unit, Istituto Tumori della Romagna I.R.S.T., Meldola, Italy, 4Radiotherapy Unit, Istituto Tumori della Romagna I.R.S.T., Meldola, Italy, 5Medical Oncology Unit, University Hospital of Parma, Parma, Italy, 6Radiotherapy Unit, University Hospital of Parma, Parma, Italy, 7Oncology, Universita degli Studi di Verona, Verona, Italy, 8Radiotherapy Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy, 9Medical Oncology Unit, Ospedale Ramazzini di Capri, Carpi, Italy, 10Department of Hematology and Oncology, Azienda Ospedaliera Universitaria di Modena, Modena, Italy, 11Radiotherapy Unit, Azienda Ospedaliera Universitaria di Modena, Modena, Italy, 12Oncologia Medica, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 13Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy, 14Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy, 15Dipartimento di Onco-Ematologia, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 16 Oncology Department, Unita Locale Socio Sanitaria 13 P.O Mirano, Mirano, Italy, 17 Medical Oncology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy, 18Clinical Cancer Center, Medical Oncology Unit, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy Background: NIVO is an anti-programmed cell death-1 (PD-1) monoclonal antibody; it might work even better when combined with SBRT improving clinical outcomes with a phenomenon known as abscopal effect. To date there are limited data on safety profile of combined SBRT and NIVO in mRCC. We report for the first time the toxicities occurred in phase II NIVES Study. Methods: This is a phase II, single arm, multicentre study in pts with mRCC with progression disease after2 prior anti-angiogenic therapies and with measurable non-brain metastatic sites, at least one of which potentially suitable for SBRT. The pts included received hypofractionated radiation in one lesion at dose of 10 Gy/3 fractions after 7 days from the first infusion of NIVO. NIVO will be given as flat dose of 240 mg on day 1 every 14 days for 6 months, then switch to 480 mg q4-weekly in responding pts until PD or unacceptable toxicity. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed severe Adverse Events (AEs) graded by CTCAE v. 4.03. Results: Sixty-nine pts were enrolled from July 2017 to March 2019 in 11 Italian centers. 79.7% of pts had clear cell histology, median age was 67 years (range 43-85), 82.6% were male. ECOG PS was 0 in 57 pts (82.6%), only 18.8% pts had received 2 previous lines of therapy. The most frequent sites of SBRT were lung (39.4% of pts), lymphonodes (16.7%) and bone (10.6%). Toxicities of grade (G) 3-4 related to NIVO were experienced in 13 pts (18.8%); all G3-4 toxicities were outside of the irradiated area. The most frequently observed G3-4 treatment-related AEs included diarrhea (5.8%), fatigue (4.3%), anemia (2.9%) and increase of amylase/lipase (2.9%). To date no G3-4 pneumonitis were observed. Six pts (8.7%) were hospitalized due to treatment-related SAEs. Overall, 5 of 69 treated pts (7.2%) discontinued therapy because of G3-4 AEs. At the time of this analysis 32/69 pts (46%) are still on treatment. Conclusions: Concurrent NIVO plus SBRT is generally well tolerated, without increased rates of common severe toxicity. Definitive data of toxicities and efficacy of the combination of immunotherapy and radiotherapy are not yet mature. Clinical trial identification: NCT03469713. Legal entity responsible for the study: GOIRC. Funding: GOIRC. Disclosure: C. Masini: Travel / Accommodation / Expenses: BMS, Janssen, Astellas, Bayer; Advisory / Consultancy: Pfizer, Novartis, Sanofi. U.F.F. De Giorgi: Research grant / Funding (institution): AstraZeneca, Roche, Sanofi; Advisory / Consultancy: Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi; Travel / Accommodation / Expenses: BMS, Ipsen, Janssen, Pfizer. S. Buti: Advisory /
Volume 30 | Supplement 5 | October 2019
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Real world experience of nivolumab therapy in metastatic renal cancer patients: A 3 year multi-centre review
J. Hack1, S.L. Hill2, J. Broadfoot3, C. Chau1, T. Geldart3, J. Gale1, K. Fife4, M. Wheater5 Oncology Department, Portsmouth Hospitals NHS Trust, Portsmouth, UK, 2Oncology Department, Southampton General Hospital, Southampton, UK, 3Oncology Department, Royal Bournemouth Hospital, Bournemouth, UK, 4Oncology Department, Cambridge University Hospitals NHS Foundation Trust - Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK, 5Oncology Department, Southampton General Hospital Southampton University Hospitals NHS Trust, Southampton, UK
1
Background: In the UK renal cancer has an incidence of around 12600 cases per year. Nivolumab is an anti-PD1 checkpoint inhibitor, which was approved in the UK for second or subsequent line treatment of advanced renal cancer in 2016. The aim of this study was to evaluate a regional experience of nivolumab use in this setting. Methods: A retrospective analysis was undertaken of patients who commenced nivolumab as monotherapy for advanced renal cancer at three Cancer Centres in South Central England between February 2016 and April 2019. Information was collated from electronic patient records and e-prescribing systems. Information was gathered on patient demographics, Heng (IMDC) prognostic scores, previous treatments, treatment toxicity, use of steroids and radiotherapy during treatment, physician assessment of response and survival data. Results: 109 eligible patients were identified. The average age was 59 with 72.5% of patients male. 67.9% (74/109) of patients had prior nephrectomy and 50.5% (55/109) had metastatic disease at diagnosis. 82.6% (90/109) had pure clear cell histology. 63.3% (69/109) received nivolumab as second-line treatment, 27.5% (30/109) as third-line treatment and 9.2% (10/109) as fourth-line and beyond. At the start of treatment 19.41% (19/103) had a ‘favourable’ risk Heng score, 61.2% (64/103) had an ‘intermediate’ risk and 18.3% (19/103) had a ‘poor’ risk. The number of Nivolumab cycles received ranged from 1-69, with a mean of 11 and median of 5. 45.9% of patients experienced toxicity of any grade, with 16.5% experiencing grade 3/4 toxicity. 24.8% (28/ 109) received radiotherapy and 40.4% (44/109) received steroids during nivolumab treatment. At response assessment 31.5% showed a response to nivolumab, 9.3% had stable disease and 59.3% had disease progression. From the start of nivolumab treatment median progression-free survival was 5.4 months, and the 12-month overall survival rate was 56.88%. 22.6% (24/109) are still receiving nivolumab. Conclusions: This review has given us important real-world data on the safety and efficacy of nivolumab which reflects the findings of the pivotal phase 3 trials that led to it’s use. Further analysis will allow us to see the effect of different factors on these outcomes. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC)
M.T. Campbell1, S. Martin2, A.L. Tam3, R.A. Sheth3, S. Singh4, K. Ahrar3, B. Slack Tidwell5, P. Rao6, J.A. Karam7, C.G. Wood8, N.M. Tannir9, E. Jonasch10, J. Gao11, A.Y. Shah8, J.M. Blando4, F. Duan4, S. Basu4, J. Allison4, P. Sharma12, S. Singh4 1 Genitourinary Medical Oncology, The M. D. Anderson Cancer Center, Houston, TX, USA, 2Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 3 Interventional Radiology, MD Anderson Cancer Center, Houston, TX, USA, 4 Immunology, MD Anderson Cancer Center, Houston, TX, USA, 5Biostatistics, MD Anderson Cancer Center, Houston, TX, USA, 6Pathology Admin, MD Anderson Cancer Center, Houston, TX, USA, 7Urology, MD Anderson Cancer Center, Houston, TX, USA, 8 Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA, 9 Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA, 10GU Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 11Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA, 12Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA Background: Cryo is an effective intervention for palliation and local control for small primary and metastatic tumours in mRCC. Pre-clinical murine tumour modeling found cryo recruits effector immune cells and synergizes with anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) to inhibit tumour rechallenge as compared to either therapy (tx) alone, leading to a prospective pilot study evaluating safety/tolerability.
doi:10.1093/annonc/mdz249 | v389
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz249.058/5576814 by guest on 26 October 2019
mony: Novartis; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Sanofi; Research grant / Funding (institution): Invectys; Research grant / Funding (institution): Philips; Research grant / Funding (institution): Evolucare; Research grant / Funding (institution): ArianaPharma; Research grant / Funding (institution): Imagia. C. Thibault: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. Y. Vano: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Pfizer MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen-Cilag; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Astellas. All other authors have declared no conflicts of interest.
Consultancy: BMS, Pfizer, MSD. M. Milella: Speaker Bureau / Expert testimony: AstraZeneca, Pfizer, EUSA Pharma. M.G. Vitale: Speaker Bureau / Expert testimony: Astellas, Ipsen, Janssen, Pierre Fabre, BMS, Pfizer, Novartis; Travel / Accommodation / Expenses: Astellas, Pfizer, Ipsen, Janssen, BMS, Novartis; Advisory / Consultancy: Janssen, BMS. G. Procopio: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer, BMS, Ipsen, MSD, Novartis, Pfizer. F. Nole: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS, Ipsen, Pfizer, Bayer, Novartis, MSD. G. Pappagallo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen, BMS, Astellas, Janssen, Bayer, Pfizer, Novartis. C. Pinto: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche, BMS, MSD, Janssen, Pfizer, Novartis, Ipsen, Lilly, Bayer. All other authors have declared no conflicts of interest.