المؤلفون: Grob, J.-J., Amonkar, M. M., Martin-Algarra, S., Demidov, L. V., Goodman, V., Grotzinger, K., Haney, P., Kämpgen, E., Karaszewska, B., Mauch, C., Miller Jr., W. H., Millward, M., Mirakhur, B., Rutkowski, P., Chiarion-Sileni, V., Swann, S., Hauschild, A.

مصطلحات موضوعية: ddc:610

الوصف: Background: In a randomized phase III study (BREAK-3), dabrafenib showed prolonged progression-free survival (PFS) (median 5.1 versus 2.7 months; hazard ratio = 0.30; 95% confidence interval 0.18–0.53; P < 0.0001) compared with dacarbazine (DTIC) in patients with BRAF V600E metastatic melanoma. Assessing how these results are transformed into a real health benefit for patients is crucial. Methods: The EORTC QLQ-C30 questionnaire assessed quality of life (QoL) at baseline and follow-up visits. Results: For DTIC, all functional dimensions except role dimension worsened from baseline at follow-up. For dabrafenib, all functionality dimensions remained stable relative to baseline or improved at week 6; mean change in seven symptom dimensions improved from baseline, with appetite loss, insomnia, nausea and vomiting, and pain showing the greatest improvement. In the DTIC arm, symptom dimensions were unchanged or worsened from baseline for all symptoms except pain (week 6), with the greatest exacerbations observed for fatigue and nausea and vomiting. Mixed-model-repeated measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements from baseline in favor of dabrafenib for emotional and social functioning, nausea and vomiting, appetite loss, diarrhea, fatigue, dyspnea, and insomnia at weeks 6 and/or 12. After crossing over to dabrafenib upon progression (n = 35), improvements in all QoL dimensions were evident after receiving dabrafenib for 6 (n = 31) to 12 (n = 25) weeks. Conclusions: This first reported QoL analysis for a BRAF inhibitor in metastatic melanoma demonstrates that the high tumor response rates and PFS superiority of dabrafenib over DTIC is not only a theoretical advantage, but also transforms in a rapid functional and symptomatic benefit for the patient. Clinical Trials.gov identifier NCT01227889.

وصف الملف: application/pdf

العلاقة: https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/7419Test; urn:nbn:de:bvb:29-opus4-74190; https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-74190Test; https://doi.org/10.1093/annonc/mdu154Test; https://opus4.kobv.de/opus4-fau/files/7419/Grob_patient.pdfTest

الإتاحة: https://doi.org/10.1093/annonc/mdu154Test
https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/7419Test
https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-74190Test
https://opus4.kobv.de/opus4-fau/files/7419/Grob_patient.pdfTest

المؤلفون: Schadendorf, D., Amonkar, M. M., Milhem, M., Grotzinger, K., Demidov, L. V., Rutkowski, P., Garbe, C., Dummer, R., Hassel, J. C., Wolter, P., Mohr, P., Trefzer, U., Lefeuvre-Plesse, C., Rutten, A., Steven, N., Ullenhag, G., Sherman, L., Wu, F. S., Patel, K., Casey, M., Robert, C.

مصطلحات موضوعية: Original article

الوصف: <$O_ST_ABS>Background<$C_ST_ABS>In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. <$O_ST_ABS>Patients and methods<$C_ST_ABS>Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. <$O_ST_ABS>Results<$C_ST_ABS>In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4–5 points with chemotherapy but improved by 2–3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8–11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4–8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11–12 points), insomnia (10–12 points), and appetite loss (1–5 points), whereas those for diarrhea worsened (15–16 points). Mixed-model repeated-measures analyses showed significant ( P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. ...

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/mdt580v1Test; http://dx.doi.org/10.1093/annonc/mdt580Test

الإتاحة: https://doi.org/10.1093/annonc/mdt580Test
http://annonc.oxfordjournals.org/cgi/content/short/mdt580v1Test

المؤلفون: Hauschild, A., Grobb, J., Demidov, L., Jouary, T., Gutzmer, R., Millward, M., Rutkowski, P., Blank, C., Miller, W., Martin-Algarra, S., Karaszewska, B., Mauch, C., Chiarion Sileni, V., Aktan, G., Haney, P., Jin, F., Legos, J., Swann, S., Chapman, P.

المصدر: Annals of Oncology ; volume 25, page iv378 ; ISSN 0923-7534

مصطلحات موضوعية: Oncology, Hematology

الإتاحة: https://doi.org/10.1093/annonc/mdu344.8Test
https://api.elsevier.com/content/article/PII:S0923753419525443?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0923753419525443?httpAccept=text/plainTest
http://academic.oup.com/annonc/article-pdf/25/suppl_4/iv378/9691345/mdu344.8.pdfTest

المؤلفون: Ribas, A. Chesney, J. Long, G. V. Kirkwood, J. M. and Dummer, R. Puzanov, I. Hoeller, C. Gajewski, T. F. and Gutzmer, R. Rutkowski, P. Demidov, L. Arenberger, P. and Shin, S. J. Ferrucci, P. F. Diede, S. J. Anderson, J. R. and Treichel, S. Chan, E. Hodi, F. S. Gogas, H. J.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od______2127::458c2e4bce13a599d82f5ec24cc47b4eTest
https://pergamos.lib.uoa.gr/uoa/dl/object/uoadl:3031626Test

المؤلفون: Gogas, H. Dréno, B. Larkin, J. Demidov, L. Stroyakovskiy, D. Eroglu, Z. Francesco Ferrucci, P. Pigozzo, J. Rutkowski, P. Mackiewicz, J. Rooney, I. Voulgari, A. Troutman, S. Pitcher, B. Guo, Y. Yan, Y. Castro, M. Mulla, S. Flaherty, K. Arance, A.

الوصف: Background: Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAFV600 wild-type advanced melanoma. Patients and methods: IMspire170 was an international, randomized, open-label, phase III study. Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed death-ligand 1 atezolizumab (840 mg every 2 weeks) in 28-day cycles or anti-programmed death-1 pembrolizumab (200 mg every 3 weeks) alone until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary outcome was progression-free survival (PFS), assessed by an independent review committee in the intention-to-treat population. Results: Between 11 December 2017, and 29 January 2019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n = 222) or pembrolizumab (n = 224). Median follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. Median PFS was 5.5 months [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI 3.7-9.6) with pembrolizumab [stratified hazard ratio 1.15 (95% CI 0.88-1.50); P = 0.30]. Hazard ratios for PFS were consistent across prespecified subgroups. In exploratory biomarker analyses, higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. The most common grade 3-5 adverse events (AEs) were increased blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), hypertension (6.4% versus 3.7%), and dermatitis acneiform (5.0% versus 0). Serious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and 20.8% with pembrolizumab. Conclusion: Cobimetinib plus atezolizumab did not improve PFS compared with pembrolizumab monotherapy in patients with BRAFV600 wild-type advanced melanoma. © 2020 European Society for Medical Oncology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od______2127::4ffcaa298e92105ffd0f42860dd18136Test
https://pergamos.lib.uoa.gr/uoa/dl/object/uoadl:3102745Test

المؤلفون: Schadendorf D., Ascierto P. A., Haanen J., Espinosa E., Demidov L., Garbe C., Guida M., Lorigan P., Chiarion-Sileni V., Gogas H., Maio M., Fierro M. T., Hoeller C., Terheyden P., Gutzmer R., Guren T. K., Bafaloukos D., Rutkowski P., Plummer R., Waterston A., Kaatz M., Mandala M., Marquez-Rodas I., Munoz-Couselo E., Dummer R., Grigoryeva E., Young T. C., Nathan P.

المساهمون: Schadendorf D., Ascierto P.A., Haanen J., Espinosa E., Demidov L., Garbe C., Guida M., Lorigan P., Chiarion-Sileni V., Gogas H., Maio M., Fierro M.T., Hoeller C., Terheyden P., Gutzmer R., Guren T.K., Bafaloukos D., Rutkowski P., Plummer R., Waterston A., Kaatz M., Mandala M., Marquez-Rodas I., Munoz-Couselo E., Dummer R., Grigoryeva E., Young T.C., Nathan P.

مصطلحات موضوعية: Advanced melanoma, Autoimmune, CNS metastasi, ECOG performance statu, Ipilimumab, Nivolumab

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31581055; info:eu-repo/semantics/altIdentifier/wos/WOS:000490764300018; volume:121; firstpage:144; lastpage:153; numberofpages:10; journal:EUROPEAN JOURNAL OF CANCER; http://hdl.handle.net/2318/1717992Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85072658755; http://www.journals.elsevier.com/european-journal-of-cancerTest/

الإتاحة: https://doi.org/10.1016/j.ejca.2019.08.014Test
http://hdl.handle.net/2318/1717992Test
http://www.journals.elsevier.com/european-journal-of-cancerTest/

المؤلفون: Schadendorf D., Di Giacomo A. M., Demidov L., Merelli B., Bondarenko I., Ascierto P. A., Herbert C., Mackiewicz A., Rutkowski P., Guminski A., Goodman G. R., Simmons B., Ye C., Hong A., Lewis K.

المساهمون: Schadendorf, D., Di Giacomo, A. M., Demidov, L., Merelli, B., Bondarenko, I., Ascierto, P. A., Herbert, C., Mackiewicz, A., Rutkowski, P., Guminski, A., Goodman, G. R., Simmons, B., Ye, C., Hong, A., Lewis, K.

مصطلحات موضوعية: Adjuvant treatment, BRAF, Health-related quality of life, Resected melanoma, Vemurafenib, Adolescent, Adult, Aged, 80 and over, Anorexia, Antineoplastic Agent, Cognitive Dysfunction, Fatigue, Female, Human, Logistic Model, Male, Melanoma, Middle Aged, Pain, Proto-Oncogene Proteins B-raf, Skin Neoplasm, Young Adult, Chemotherapy, Adjuvant, Dermatologic Surgical Procedure, Quality of Life

الوصف: Aim of study: The aim of the study was to assess the impact of treatment with adjuvant vemurafenib monotherapy on health-related quality of life (HRQOL) in patients with resected stage IIC–IIIC melanoma. Methods: The phase 3 BRIM8 study (NCT01667419) randomised patients with BRAFV600 mutation–positive resected stage IIC–IIIC melanoma to 960 mg of vemurafenib twice daily or matching placebo for 52 weeks (13 × 28-day cycles). Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3 at baseline, cycle 1 (days 1, 15 and 22), cycle 2 (days 1 and 15), day 1 of every subsequent 4-week cycle, the end-of-treatment visit and each visit during the follow-up period. Results: Completion rates for the EORTC QLQ-C30 questionnaire were high (>80%). There was a mean decline in the global health status (GHS)/quality of life (QOL) score of 17.4 (±22.9) and 17.3 (±24.1) points at days 15 and 22 of cycle 1, respectively, among vemurafenib-treated patients who recovered to approximately 10 points below baseline for the remainder of the treatment period. A similar trend was observed in all functional scales except for cognitive function (<10-point change from baseline at all visits) and in the symptom scores for appetite loss, fatigue and pain. As observed for the GHS/QOL score, all scores rapidly returned to baseline after completion of planned vemurafenib treatment or treatment discontinuation. Conclusions: The schedule of HRQOL assessments allowed for an accurate and complete evaluation of the impact of acute treatment-related symptoms. Vemurafenib-treated patients experience clinically meaningful moderate worsening in some treatment- or disease-related symptoms and GHS/QOL that resolve over time.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31704549; info:eu-repo/semantics/altIdentifier/wos/WOS:000499645600019; volume:123; firstpage:155; lastpage:161; numberofpages:7; journal:EUROPEAN JOURNAL OF CANCER; http://hdl.handle.net/11365/1119739Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85074348441

الإتاحة: https://doi.org/10.1016/j.ejca.2019.09.019Test
http://hdl.handle.net/11365/1119739Test

المؤلفون: Nathan P, Ascierto PA, Haanen J, Espinosa E, Demidov L, Garbe C, Guida M, Lorigan P, Chiarion-Sileni V, Gogas H, Maio M, Fierro MT, Hoeller C, Terheyden P, Gutzmer R, Guren TK, Bafaloukos D, Rutkowski P, Plummer R, Waterston A, Kaatz M, MANDALA' M, Marquez-Rodas I, Muñoz-Couselo E, Dummer R, Grigoryeva E, Young TC, Schadendorf D

المساهمون: Nathan, P, Ascierto, Pa, Haanen, J, Espinosa, E, Demidov, L, Garbe, C, Guida, M, Lorigan, P, Chiarion-Sileni, V, Gogas, H, Maio, M, Fierro, Mt, Hoeller, C, Terheyden, P, Gutzmer, R, Guren, Tk, Bafaloukos, D, Rutkowski, P, Plummer, R, Waterston, A, Kaatz, M, Mandala', M, Marquez-Rodas, I, Muñoz-Couselo, E, Dummer, R, Grigoryeva, E, Young, Tc, Schadendorf, D

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000486628600018; journal:EUROPEAN JOURNAL OF CANCER; http://hdl.handle.net/11391/1480919Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85070912965

الإتاحة: http://hdl.handle.net/11391/1480919Test

المؤلفون: Schadendorf D, Ascierto PA, Haanen J, Espinosa E, Demidov L, Garbe C, Guida M, Lorigan P, Chiarion-Sileni V, Gogas H, Maio M, Fierro MT, Hoeller C, Terheyden P, Gutzmer R, Guren TK, Bafaloukos D, Rutkowski P, Plummer R, Waterston A, Kaatz M, MANDALA' M, Marquez-Rodas I, Muñoz-Couselo E, Dummer R, Grigoryeva E, Young TC, Nathan P

المساهمون: Schadendorf, D, Ascierto, Pa, Haanen, J, Espinosa, E, Demidov, L, Garbe, C, Guida, M, Lorigan, P, Chiarion-Sileni, V, Gogas, H, Maio, M, Fierro, Mt, Hoeller, C, Terheyden, P, Gutzmer, R, Guren, Tk, Bafaloukos, D, Rutkowski, P, Plummer, R, Waterston, A, Kaatz, M, Mandala', M, Marquez-Rodas, I, Muñoz-Couselo, E, Dummer, R, Grigoryeva, E, Young, Tc, Nathan, P

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000490764300018; journal:EUROPEAN JOURNAL OF CANCER; http://hdl.handle.net/11391/1480881Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85072658755

الإتاحة: http://hdl.handle.net/11391/1480881Test

المؤلفون: Gogas, H, Dréno, B, Larkin, J, Demidov, L, Stroyakovskiy, D, Eroglu, Z, Francesco Ferrucci, P, Pigozzo, J, Rutkowski, P, Mackiewicz, J, Rooney, I, Voulgari, A, Troutman, S, Pitcher, B, Guo, Y, Yan, Y, Castro, M, Mulla, S, Flaherty, K, Arance, A

المساهمون: National and Kapodistrian University of Athens (NKUA), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Royal Marsden NHS Foundation Trust, N.N. Blokhin Russian Cancer Research Center, Moscow City Oncology Hospital No. 62 Moscow, Russia (MCOH), H. Lee Moffitt Cancer Center and Research Institute, European Institute of Oncology Milan (ESMO), Veneto Institute of Oncology IOV-IRCCS Padua, Italy, Maria Sklodowska-Curie National Research Institute of Oncology Krakow, Poland, Poznan University of Medical Sciences Poland (PUMS), Genentech, Inc. San Francisco, Roche Products Ltd, F. Hoffmann-La Roche Basel, Massachusetts General Hospital Cancer Center Boston, MA, USA, Harvard Medical School Boston (HMS), Hospital Clinic Barcelona, Spain

المصدر: ISSN: 0923-7534.

مصطلحات موضوعية: atezolizumab, cobimetinib, pembrolizumab, melanoma, BRAF wild-type, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Background: Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAF V600 wild-type advanced melanoma. Patients and methods: IMspire170 was an international, randomized, open-label, phase III study. Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed death-ligand 1 atezolizumab (840 mg every 2 weeks) in 28-day cycles or anti-programmed death-1 pembrolizumab (200 mg every 3 weeks) alone until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary outcome was progression-free survival (PFS), assessed by an independent review committee in the intention-to-treat population. Results: Between 11 December 2017, and 29 January 2019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n ¼ 222) or pembrolizumab (n ¼ 224). Median follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. Median PFS was 5.5 months [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI 3.7-9.6) with pembrolizumab [stratified hazard ratio 1.15 (95% CI 0.88-1.50); P ¼ 0.30]. Hazard ratios for PFS were consistent across prespecified subgroups. In exploratory biomarker analyses, higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. The most common grade 3-5 adverse events (AEs) were increased blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), hypertension (6.4% versus 3.7%), and dermatitis acneiform (5.0% versus 0). Serious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33309774; inserm-03710214; https://inserm.hal.science/inserm-03710214Test; https://inserm.hal.science/inserm-03710214/documentTest; https://inserm.hal.science/inserm-03710214/file/PIIS092375342043203X.pdfTest; PUBMED: 33309774

الإتاحة: https://doi.org/10.1016/j.annonc.2020.12.004Test
https://inserm.hal.science/inserm-03710214Test
https://inserm.hal.science/inserm-03710214/documentTest
https://inserm.hal.science/inserm-03710214/file/PIIS092375342043203X.pdfTest