المؤلفون: Bernies van der Hiel, John B.A.G. Haanen, Marcel P.M. Stokkel, Daniel S. Peeper, Connie R. Jimenez, Jos H. Beijnen, Bart A. van de Wiel, Ronald Boellaard, Alfons J.M. van den Eertwegh, REPOSIT study group

المصدر: BMC Cancer, Vol 17, Iss 1, Pp 1-13 (2017)

مصطلحات موضوعية: Stage IIIc/IV melanoma, Resistance, BRAF inhibitor, MEK inhibitor, 18F-FDG, 18F-FLT, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3′-deoxy-3’L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. Discussion The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated melanoma to molecular changes within the tumor. We will be able to correlate both 18F-FDG and 18F-FLT PET to outcome and decide on the best modality to predict long-term remissions to combined BRAF/MEK-inhibitors. Results coming from this study may help in identifying responders from non-responders early after the initiation of therapy and reveal early development of resistance to vemurafenib/cobimetinib. Furthermore, we believe that the results can be fundamental for further optimizing individual patient treatment. Trial registration Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12885-017-3626-5Test; https://doaj.org/toc/1471-2407Test

الوصول الحر: https://doaj.org/article/77ba6f1ed208421eb8ac731a793a38eaTest

المؤلفون: Annegien Broeks, Sofie Wilgenhof, John B A G Haanen, Karolina Sikorska, Christian U Blank, Judith M Versluis, Jan Willem B de Groot, Esmee P Hoefsmit, Elisa A Rozeman, Petros Dimitriadis, Aysegul Sari, Daan van den Broek, Disha Rao, Ruben Lacroix, Lindsay G Grijpink-Ongering, Marta Lopez-Yurda, Birthe C Heeres, Bart A van de Wiel, Claudie Flohil, Stijn W T P J Heijmink, Marieke A Vollebergh, Johannes V van Thienen

المصدر: Journal for ImmunoTherapy of Cancer, Vol 11, Iss 7 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Continuous combination of MAPK pathway inhibition (MAPKi) and anti-programmed death-(ligand) 1 (PD-(L)1) showed high response rates, but only limited improvement in progression-free survival (PFS) at the cost of a high frequency of treatment-related adverse events (TRAE) in patients with BRAFV600-mutated melanoma. Short‐term MAPKi induces T-cell infiltration in patients and is synergistic with anti-programmed death-1 (PD‐1) in a preclinical melanoma mouse model. The aim of this phase 2b trial was to identify an optimal regimen of short-term MAPKi with dabrafenib plus trametinib in combination with pembrolizumab.Methods Patients with treatment-naïve BRAFV600E/K-mutant advanced melanoma started pembrolizumab 200 mg every 3 weeks. In week 6, patients were randomized to continue pembrolizumab only (cohort 1), or to receive, in addition, intermittent dabrafenib 150 mg two times per day plus trametinib 2 mg one time per day for two cycles of 1 week (cohort 2), two cycles of 2 weeks (cohort 3), or continuously for 6 weeks (cohort 4). All cohorts continued pembrolizumab for up to 2 years. Primary endpoints were safety and treatment-adherence. Secondary endpoints were objective response rate (ORR) at week 6, 12, 18 and PFS.Results Between June 2016 and August 2018, 33 patients with advanced melanoma have been included and 32 were randomized. Grade 3–4 TRAE were observed in 12%, 12%, 50%, and 63% of patients in cohort 1, 2, 3, and 4, respectively. All planned targeted therapy was given in 88%, 63%, and 38% of patients in cohort 2, 3, and 4. ORR at week 6, 12, and 18 were 38%, 63%, and 63% in cohort 1; 25%, 63%, and 75% in cohort 2; 25%, 50%, and 75% in cohort 3; and 0%, 63%, and 50% in cohort 4. After a median follow-up of 43.5 months, median PFS was 10.6 months for pembrolizumab monotherapy and not reached for patients treated with pembrolizumab and intermittent dabrafenib and trametinib (p=0.17). The 2-year and 3-year landmark PFS were both 25% for cohort 1, both 63% for cohort 2, 50% and 38% for cohort 3 and 75% and 60% for cohort 4.Conclusions The combination of pembrolizumab plus intermittent dabrafenib and trametinib seems more feasible and tolerable than continuous triple therapy. The efficacy is promising and appears to be favorable over pembrolizumab monotherapy.Trial registration number NCT02625337.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/11/7/e006821.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/85f4bb454d4548b7b0eddc4aff9da5e2Test

المؤلفون: Viola, Franke, Emma H A, Stahlie, Willem M C, Klop, Charlotte L, Zuur, Danique M S, Berger, Bernies, van der Hiel, Bart A, van de Wiel, Michel W J M, Wouters, Winan J, van Houdt, Alexander C J, van Akkooi

المصدر: Melanoma Research. 33:66-70

مصطلحات موضوعية: Cancer Research, Oncology, Dermatology

الوصف: Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1, intralesionally administered in patients with stage IIIB/C-IVM1a unresectable melanoma. When surgery is not a treatment option in the head and neck region, T-VEC can be an elegant alternative to systemic immunotherapy. Ten patients with metastatic melanoma in the head and neck region started treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events (AEs), and baseline characteristics. For response evaluation, we used clinical evaluation with photography, 3-monthly PET/computed tomography (PET/CT) using 18F-fluoro-2-D-deoxyglucose, and histological biopsies. Median age at baseline was 78.2 (35-97) years with a median follow-up of 11.6months. Of these 10 patients, 5 had a complete response (CR), 3 had a partial response, 1 had stable disease and 1 showed progressive disease (PD) as their best response. Best overall response rate (ORR) was 80%. Median progression-free survival was 10.8 months (95% confidence interval, 2.2-19.4). Grade 1 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms, and injection site pain. PET-CT and histological biopsies proved to be clinically useful tools to evaluate treatment response for T-VEC monotherapy, confirming pCR or PD to stage IV disease requiring systemic treatment. ORR for T-VEC monotherapy for melanoma in the head and neck region at our institute was 80% with 50% achieving a CR. This realworld data demonstrates promising results and suggests T-VEC can be an alternative to systemic therapy in this select, mostly elderly patient population.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::435776695b7927730672cd3cf881b871Test
https://doi.org/10.1097/cmr.0000000000000866Test

المؤلفون: Viola, Franke, Emma H A, Stahlie, Bernies, van der Hiel, Bart A, van de Wiel, Michel W J M, Wouters, Winan J, van Houdt, Alexander C J, van Akkooi

المصدر: Journal of Immunotherapy. 45:263-266

مصطلحات موضوعية: Oncolytic Virotherapy, Pharmacology, Biological Products, Cancer Research, Skin Neoplasms, Chronic Disease, Immunology, Humans, Immunology and Allergy, Herpesvirus 1, Human, Immunotherapy, Melanoma

الوصف: Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus type 1, which can be administered intralesionally in patients with stage IIIB/C-IVM1a (American Joint Committee of Cancer; AJCC 7th edition) unresectable melanoma. In the case of disease recurrence, T-VEC can be re-introduced for the same category of patients. Five patients with recurrent disease after a prior achieved complete response (CR) recommenced treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events and baseline characteristics. All 5 patients that were re-treated with T-VEC presented with in-transit metastases on the lower limb. Median age at baseline was 72.1 years with a median follow-up time of 30.4 months. Histologically proven CR was achieved after a median of 8 T-VEC courses on the initial exposure. Duration of response (time between first CR and recurrence) varied between 3.8 and 14.2 months. All 5 patients achieved a histologically and/or positron emission tomography/computed tomography proven CR again after re-introduction of T-VEC with a median of 5 courses. One patient (20%) developed a second recurrence and is currently still on treatment with T-VEC. No patients developed distant metastases. Grade 1 adverse events occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site pain. Response to re-introduction of T-VEC monotherapy in this select patient population is promising. This real world data on re-introduction of T-VEC monotherapy in stage IIIB/C-IVM1a melanoma suggests T-VEC could be a treatment option for chronic disease control.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f75071dad0d2cc90452547d85ba79a7Test
https://doi.org/10.1097/cji.0000000000000423Test

المؤلفون: Irene L.M. Reijers, Disha Rao, Judith M. Versluis, Alexander M. Menzies, Petros Dimitriadis, Michel W. Wouters, Andrew J. Spillane, Willem M.C. Klop, Annegien Broeks, Linda J.W. Bosch, Marta Lopez-Yurda, Winan J. van Houdt, Robert V. Rawson, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Sten Cornelissen, Jasper Bouwman, Joyce Sanders, Elsemieke Plasmeijer, Yannick S. Elshot, Richard A. Scolyer, Bart A. van de Wiel, Daniel S. Peeper, Alexander C.J. van Akkooi, Georgina V. Long, Christian U. Blank

المساهمون: Oral and Maxillofacial Surgery, Dermatology, Graduate School, AII - Infectious diseases, AII - Inflammatory diseases, CCA - Cancer Treatment and Quality of Life

المصدر: Reijers, I L M, Rao, D, Versluis, J M, Menzies, A M, Dimitriadis, P, Wouters, M W, Spillane, A J, Klop, W M C, Broeks, A, Bosch, L J W, Lopez-Yurda, M, van Houdt, W J, Rawson, R V, Grijpink-Ongering, L G, Gonzalez, M, Cornelissen, S, Bouwman, J, Sanders, J, Plasmeijer, E, Elshot, Y S, Scolyer, R A, van de Wiel, B A, Peeper, D S, van Akkooi, A C J, Long, G V & Blank, C U 2023, ' IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma ', Journal of Experimental Medicine, vol. 220, no. 5, e20221952 . https://doi.org/10.1084/jem.20221952Test
Journal of experimental medicine, 220(5):e20221952. Rockefeller University Press
Journal of Experimental Medicine, 220(5):e20221952. Rockefeller University Press

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17999c5aac89a5332bee79a05cb4e596Test
https://doi.org/10.1084/jem.20221952Test

المؤلفون: Bernies, van der Hiel, Stephanie A, Blankenstein, Else A, Aalbersberg, Maurits, Wondergem, Marcel P M, Stokkel, Bart A, van de Wiel, W Martin C, Klop, Alexander C J, van Akkooi, John B, Haanen

المصدر: Clinical Nuclear Medicine. 47:583-589

مصطلحات موضوعية: Mitogen-Activated Protein Kinase Kinases, Proto-Oncogene Proteins B-raf, Skin Neoplasms, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Humans, Radiology, Nuclear Medicine and imaging, General Medicine, Radiopharmaceuticals, Melanoma, Protein Kinase Inhibitors, Neoadjuvant Therapy

الوصف: The aim of this study was to investigate whether 18F-FDG PET/CT can predict histopathological response or recurrence in BRAF-mutated unresectable locally advanced stage III melanoma treated with neoadjuvant BRAF/MEK inhibition followed by resection and the value of PET in detecting early recurrence after resection.Twenty BRAF-mutated, unresectable stage III melanoma patients received BRAF/MEK inhibitors before surgery. 18F-FDG PET/CT was performed at baseline and 2 and 8 weeks after initiation of therapy. After resection, PET/CT was performed at specific time points during 5 years of follow-up. Pathological response was assessed on the dissection specimen. Response monitoring was measured with SUVmax, SUVpeak, MATV, and TLG and according to EORTC and PERCIST criteria.Pathological response was assessed in 18 patients. Nine patients (50%) had a pathologic complete or near-complete response, and 9 (50%) had a pathologic partial or no response. EORTC or PERCIST response measurements did not correspond with pathologic outcome. SUVmax, SUVpeak, MATV, and TLG at all time points and absolute or percentage change among the 3 initial time points did not differ between the groups.During follow-up, 8 of 17 patients with R0 resection developed a recurrence, 6 recurrences were detected with imaging only, 4 of which with PET/CT in less than 6 months after surgery. PET parameters before surgery did not predict recurrence.Baseline 18F-FDG PET or PET response in previous unresectable stage III melanoma patients seems not useful to predict pathologic response after neoadjuvant BRAF/MEK inhibitors treatment. However, PET/CT seems valuable in detecting recurrence early after R0 resection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f426e969687282483d368cca4afa0fcTest
https://doi.org/10.1097/rlu.0000000000004217Test

المؤلفون: Irene L. M. Reijers, Alexander M. Menzies, Alexander C. J. van Akkooi, Judith M. Versluis, Noëlle M. J. van den Heuvel, Robyn P. M. Saw, Thomas E. Pennington, Ellen Kapiteijn, Astrid A. M. van der Veldt, Karijn P. M. Suijkerbuijk, Geke A. P. Hospers, Elisa A. Rozeman, Willem M. C. Klop, Winan J. van Houdt, Karolina Sikorska, Jos A. van der Hage, Dirk J. Grünhagen, Michel W. Wouters, Arjen J. Witkamp, Charlotte L. Zuur, Judith M. Lijnsvelt, Alejandro Torres Acosta, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Katarzyna Jóźwiak, Carolien Bierman, Kerwin F. Shannon, Sydney Ch’ng, Andrew J. Colebatch, Andrew J. Spillane, John B. A. G. Haanen, Robert V. Rawson, Bart A. van de Wiel, Lonneke V. van de Poll-Franse, Richard A. Scolyer, Annelies H. Boekhout, Georgina V. Long, Christian U. Blank

المساهمون: Medical and Clinical Psychology, Oral and Maxillofacial Surgery, Medical Oncology, Radiology & Nuclear Medicine, Surgery, Guided Treatment in Optimal Selected Cancer Patients (GUTS)

المصدر: Nature Medicine, 28(6), 1178-+. NATURE PORTFOLIO
Nature Medicine, 28(6), 1178-1188. Nature Publishing Group
Nature Medicine
Nature medicine, 28(6), 1178-1188. Nature Publishing Group
Nature Medicine, 28. Nature Publishing Group

مصطلحات موضوعية: Skin Neoplasms, General Medicine, BIOMARKER ANALYSES, Ipilimumab, Neoadjuvant Therapy, General Biochemistry, Genetics and Molecular Biology, MORBIDITY, Nivolumab, QUALITY-OF-LIFE, Antineoplastic Combined Chemotherapy Protocols, Quality of Life, BIOPSY, SURVIVAL, Humans, AXILLARY, Neoplasm Recurrence, Local, IMMUNOTHERAPY, Melanoma, DISSECTION, SENTINEL LYMPH-NODE, Neoplasm Staging

الوصف: Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg-1 and nivolumab 3 mg kg-1. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3-4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67d79d3cfe1f3c168f561afa30efdc6cTest
https://doi.org/10.1038/s41591-022-01851-xTest

المؤلفون: Bart A. van de Wiel, Judith M. Versluis, Robyn P. M. Saw, Sydney Ch'ng, C. Blank, Bastian Schilling, Irene L.M. Reijers, Richard A. Scolyer, Georgina V. Long, Michel W.J.M. Wouters, Alexander C.J. van Akkooi, Elisa A. Rozeman, Alexander M. Menzies

المصدر: European Journal of Cancer. 148:51-57

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Ipilimumab, Metastasis, Neoplasms, Multiple Primary, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Melanoma, Lymph node, Neoadjuvant therapy, Aged, Neoplasm Staging, Retrospective Studies, business.industry, Middle Aged, medicine.disease, Neoadjuvant Therapy, Survival Rate, Clinical trial, Nivolumab, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Lymphadenectomy, Neoplasm Recurrence, Local, business, Follow-Up Studies, medicine.drug

الوصف: Background Patients with synchronous clinical stage III melanoma can present with primary melanoma lesions, locally recurrent melanoma or in-transit metastases. Neoadjuvant ipilimumab plus nivolumab induces high pathologic response rates and an impressive relapse-free survival in patients with nodal macroscopic stage III melanoma. Whether primary site melanoma and in-transit metastases respond similarly to lymph node metastases with neoadjuvant immunotherapy is largely unknown. Such data would clarify whether surgical excision of these melanoma lesions should be performed before neoadjuvant therapy or whether it could be deferred and performed in conjunction with lymphadenectomy following neoadjuvant immunotherapy. Patients Patients with synchronous clinical stage III melanoma were identified from the OpACIN, OpACIN-neo and PRADO neoadjuvant trials, where all patients were treated with ipilimumab plus nivolumab. An additional case treated outside those clinical trials was included. Results Seven patients were identified; six patients had a concordant response in primary site melanoma lesions or in-transit metastasis and the lymph node metastases. One patient had concordant progression in both the primary and nodal tumour lesions and developed stage IV disease during neoadjuvant treatment, and thus, no resection was performed. Conclusion Pathologic response following neoadjuvant ipilimumab plus nivolumab in primary site melanoma lesions or in-transit metastasis is concordant with a response in the lymph node metastases, indicating that there may be no need to perform upfront surgery to these melanoma lesions prior to neoadjuvant treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0cd6cfcc041a55a4244871ca4c62202Test
https://doi.org/10.1016/j.ejca.2021.02.012Test

المؤلفون: Emma H.A. Stahlie, Evalyn E.A.P. Mulder, Sophie Reijers, Sara Balduzzi, Charlotte L. Zuur, Willem M.C. Klop, Bernies van der Hiel, Bart A. Van de Wiel, Michel W.J.M. Wouters, Yvonne M. Schrage, Winan J. van Houdt, Dirk J. Grunhagen, Alexander C.J. van Akkooi

المساهمون: Surgery, Medical Oncology

المصدر: Critical Reviews in Oncology/Hematology, 175. ELSEVIER SCIENCE INC
Critical Reviews in Oncology/Hematology, 175:103705. Elsevier Ireland Ltd

مصطلحات موضوعية: Oncolytic Virotherapy, Biological Products, T-VEC, Skin Neoplasms, Oncology, Humans, Metastatic, Herpesvirus 1, Human, Hematology, Immunotherapy, Melanoma

الوصف: Single-agent Talimogene Laherparepvec (T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying response rates. The purpose of this systematic review and meta-analysis was to investigate the efficacy and safety of T-VEC. Of 341 publications that were identified, eight studies with a total of 642 patients were included. In patients with stage IIIB-IVM1a, the pooled complete- and overall response rate (CRR and ORR) were 41% and 64%, respectively. In patients with stage IIIB-IVM1c, the pooled CRR and ORR were 30% and 44%, respectively. In patients with stage IVM1b and IVM1c, the pooled CRR and ORR were 4% and 9%, respectively. Adverse events (AEs) were seen in 41–100% of all patients and 0–11% of AEs were severe. In conclusion, single agent T-VEC achieves the highest response rates in patients with early metastatic melanoma and is well-tolerated with generally only mild toxicities.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afda418f16f959e55733a43646188c96Test
https://doi.org/10.1016/j.critrevonc.2022.103705Test

المؤلفون: Christian U. Blank, Rodabe N. Amaria, Jennifer A. Wargo, Bart A. van de Wiel, Georgina V. Long, Hussein Abdul-Hassan Tawbi, Alexander C. Huang, Xiaowei Xu, Richard A. Scolyer, Tara C. Mitchell, Giorgos C. Karakousis, Alexander C.J. van Akkooi, Michael A. Davies, Andrew J. Spillane, Elisa A. Rozeman, Alexander M. Menzies, Robyn P. M. Saw, Michael T. Tetzlaff, Ahmad A. Tarhini, Thomas E. Pennington, Elizabeth M. Burton, Paolo A. Ascierto, Serigne Lo

المصدر: Nature Medicine. 27:301-309

مصطلحات موضوعية: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Surrogate endpoint, Melanoma, medicine.medical_treatment, Ipilimumab, General Medicine, Immunotherapy, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Targeted therapy, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Nivolumab, business, Neoadjuvant therapy, medicine.drug

الوصف: The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::826ffd3ff8235e1e6c027f5367069a0cTest
https://doi.org/10.1038/s41591-020-01188-3Test