المؤلفون: McDermott, David F., Lee, Jae Lyun, Bjarnason, Georg A., Larkin, James M.G., Gafanov, Rustem A., Kochenderfer, Mark D., Jensen, Niels Viggo, Donskov, Frede, Malik, Jahangeer, Poprach, Alexandr, Tykodi, Scott S., Alonso-Gordoa, Teresa, Cho, Daniel C., Geertsen, Poul F., Climent Duran, Miguel Angel, DiSimone, Christopher, Silverman, Rachel Kloss, Perini, Rodolfo F., Schloss, Charles, Atkins, Michael B.

المصدر: McDermott , D F , Lee , J L , Bjarnason , G A , Larkin , J M G , Gafanov , R A , Kochenderfer , M D , Jensen , N V , Donskov , F , Malik , J , Poprach , A , Tykodi , S S , Alonso-Gordoa , T , Cho , D C , Geertsen , P F , Climent Duran , M A , DiSimone , C , Silverman , R K , Perini , R F , Schloss , C & Atkins , M B 2021 , ' Open-Label, ....

مصطلحات موضوعية: Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized/therapeutic use, Antineoplastic Agents, Immunological/therapeutic use, Carcinoma, Renal Cell/drug therapy, Female, Follow-Up Studies, Humans, Kidney Neoplasms/drug therapy, Male, Middle Aged, Non-Randomized Controlled Trials as Topic, Prognosis, Survival Rate

الوصف: PURPOSE: Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS: In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS: In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION: Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.

وصف الملف: application/pdf

العلاقة: https://pure.au.dk/portal/en/publications/bae5aee9-7f1b-4552-855b-cfdb62d318f9Test

الإتاحة: https://doi.org/10.1200/JCO.20.02363Test
https://pure.au.dk/portal/en/publications/bae5aee9-7f1b-4552-855b-cfdb62d318f9Test
https://pure.au.dk/ws/files/274416924/jco.20.02363.pdfTest
http://www.scopus.com/inward/record.url?scp=85103228704&partnerID=8YFLogxKTest

المؤلفون: Motzer, Robert, Alekseev, Boris, Rha, Sun-Young, Porta, Camillo, Eto, Masatoshi, Powles, Thomas, Grünwald, Viktor, Hutson, Thomas E, Kopyltsov, Evgeny, Méndez-Vidal, María J, Kozlov, Vadim, Alyasova, Anna, Hong, Sung-Hoo, Kapoor, Anil, Alonso Gordoa, Teresa, Merchan, Jaime R, Winquist, Eric, Maroto, Pablo, Goh, Jeffrey C, Kim, Miso, Gurney, Howard, Patel, Vijay, Peer, Avivit, Procopio, Giuseppe, Takagi, Toshio, Melichar, Bohuslav, Rolland, Frederic, De Giorgi, Ugo, Wong, Shirley, Bedke, Jens, Schmidinger, Manuela, Dutcus, Corina E, Smith, Alan D, Dutta, Lea, Mody, Kalgi, Perini, Rodolfo F, Xing, Dongyuan, Choueiri, Toni K, Galamaga, Rob

المصدر: ENT and Skull Base Surgery

مصطلحات موضوعية: Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Everolimus, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Phenylurea Compounds, Programmed Cell Death 1 Receptor, Progression-Free Survival, Protein Kinase Inhibitors, Quinolines, Sunitinib, Survival Analysis

الوصف: BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

العلاقة: https://scholar.barrowneuro.org/ent-and-skull-base-surgery/23Test

الإتاحة: https://doi.org/10.1056/NEJMoa2035716Test
https://scholar.barrowneuro.org/ent-and-skull-base-surgery/23Test

المؤلفون: Grande, Enrique, Teulé, Alex, Alonso-Gordoa, Teresa, Jiménez-Fonseca, Paula, Benavent, Marta, Capdevila, Jaume, Custodio, Ana, Vera, Ruth, Munarriz, Javier, La Casta, Adelaida, Díez, Juan José, Gajate, Pablo, Molina-Cerrillo, Javier, Matos, Ignacio, Cristóbal, Eva María, Ruffinelli, José C, Palacios, José, García-Carbonero, Rocío

مصطلحات موضوعية: Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, Pancreatic Neoplasms, Piperazines, Pyridines, Spain

الوصف: Palbociclib demonstrated no detectable activity in molecularly unselected and heavily pretreated patients with advanced grade 1/2 pancreatic neuroendocrine tumors. Predictive biomarkers that improve patient selection should be investigated in future studies of palbociclib. Palbociclib, a CDK4/6 inhibitor, has shown in vitro activity in pancreatic neuroendocrine tumor (pNET) cell lines. Here we prospectively assessed the activity and safety of palbociclib in monotherapy in metastatic refractory pNETs. This was a nonrandomized, open-label, phase II study of patients with metastatic grade (G)1/2 pNETs recruited from 10 centers in Spain. Palbociclib 125 mg was orally administered once daily for 21 of 28 days until disease progression or unacceptable toxicity. Twenty-one patients were included; 52.4% were men, and median age was 57.4 years (range, 37.4-73.4). Patients had previously received a median of three prior lines of systemic therapy (range, 1-10) for advanced disease (somatostatin analogues, 71.4%; sunitinib, 81.0%; everolimus, 47.6%; chemotherapy, 47.6%). Nineteen patients were evaluated for objective response rate (ORR), with a median follow-up of 12.4 months (range, 7.53-19.33). No objective and confirmed responses were observed (0%); 11 (57.9%) patients had stable disease, and 6 of them lasted more than 6 months; 8 (42.1%) patients had disease progression as best response. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 0-14.4) and median overall survival (OS) was 18.7 months (95% CI, 7.4-29.9; Fig. 1). Most frequent toxicities of any grade were asthenia (76.2%), neutropenia (42.9%), diarrhea (33.3%), and nausea (33.3%). Five (23.8%) patients developed G3-4 neutropenia and two (9.5%) patients developed G3-4 thrombocytopenia. Lack of activity was observed with palbociclib as a single agent in molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs.

العلاقة: http://hdl.handle.net/10668/15086Test; PMC7485337; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485337/pdfTest

الإتاحة: https://doi.org/10.1634/theoncologist.2020-0033Test
http://hdl.handle.net/10668/15086Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485337/pdfTest

المؤلفون: Carmona-Bayonas, Alberto, Jiménez-Fonseca, Paula, Lamarca, Ángela, Barriuso, Jorge, Castaño, Ángel, Benavent, Marta, Alonso, Vicente, Riesco-Martínez, María Del Carmen, Alonso-Gordoa, Teresa, Custodio, Ana, Sánchez Cánovas, Manuel, Hernando Cubero, Jorge, López, Carlos, Lacasta, Adelaida, Fernández Montes, Ana, Marazuela, Mónica, Crespo, Guillermo, Escudero, Pilar, Diaz, José Ángel, Feliciangeli, Eduardo, Gallego, Javier, Llanos, Marta, Segura, Ángel, Vilardell, Felip, Percovich, Juan Carlos, Grande, Enrique, Capdevila, Jaume, Valle, Juan W, García-Carbonero, Rocío

مصطلحات موضوعية: Adolescent, Adult, Cohort Studies, Female, Hormones, Humans, Male, Neuroendocrine Tumors, Progression-Free Survival, Retrospective Studies, Somatostatin, Survival Analysis, Young Adult

الوصف: Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in ...

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/10668/14373Test; PMC6768612; https://doi.org/10.1200/jco.19.00980Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768612/pdfTest

الإتاحة: https://doi.org/10.1200/JCO.19.00980Test
https://doi.org/10.1200/jco.19.00980Test
http://hdl.handle.net/10668/14373Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768612/pdfTest

المؤلفون: Solis-Hernandez, Mª Pilar, Fernandez Del Valle, Ana, Carmona-Bayonas, Alberto, Garcia-Carbonero, Rocio, Custodio, Ana, Benavent, Marta, Alonso Gordoa, Teresa, Nuñez-Valdovino, Bárbara, Sanchez Canovas, Manuel, Matos, Ignacio, Alonso, Vicente, Lopez, Carlos, Viudez, Antonio, Izquierdo, Marta, Calvo-Temprano, David, Grande, Enrique, Capdevila, Jaume, Jimenez-Fonseca, Paula

مصطلحات موضوعية: Adult, Aged, 80 and over, Antineoplastic Agents, Confidence Intervals, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, Pancreatic Neoplasms, Progression-Free Survival, Proportional Hazards Models, Prospective Studies, Response Evaluation Criteria in Solid Tumors, Sunitinib, Tomography, X-Ray Computed, Tumor Burden, Young Adult

الوصف: The purpose of our study was to analyse the usefulness of Choi criteria versus RECIST in patients with pancreatic neuroendocrine tumours (PanNETs) treated with sunitinib. A multicentre, prospective study was conducted in 10 Spanish centres. Computed tomographies, at least every 6 months, were centrally evaluated until tumour progression. One hundred and seven patients were included. Median progression-free survival (PFS) by RECIST and Choi were 11.42 (95% confidence interval [CI], 9.7-15.9) and 15.8 months (95% CI, 13.9-25.7). PFS by Choi (Kendall's τ = 0.72) exhibited greater correlation with overall survival (OS) than PFS by RECIST (Kendall's τ = 0.43). RECIST incorrectly estimated prognosis in 49.6%. Partial response rate increased from 12.8% to 47.4% with Choi criteria. Twenty-four percent of patients with progressive disease according to Choi had stable disease as per RECIST, overestimating treatment effect. Choi criteria predicted PFS/OS. Changes in attenuation occurred early and accounted for 21% of the variations in tumour volume. Attenuation and tumour growth rate (TGR) were associated with improved survival. Choi criteria were able to capture sunitinib's activity in a clinically significant manner better than RECIST; their implementation in standard clinical practice shall be strongly considered in PanNET patients treated with this drug.

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/10668/14466Test; PMC6889276; https://www.nature.com/articles/s41416-019-0558-7.pdfTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889276/pdfTest

الإتاحة: https://doi.org/10.1038/s41416-019-0558-7Test
http://hdl.handle.net/10668/14466Test
https://www.nature.com/articles/s41416-019-0558-7.pdfTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889276/pdfTest

المؤلفون: Climent, Miguel A, Font, Albert, Durán, Ignacio, Puente, Javier, José Méndez-Vidal, María, Sáez, María Isabel, Santander Lobera, Carmen, Ángel Arranz Arija, Jóse, González-Del-Alba, Aranzazu, Sánchez-Hernandez, Alfredo, Juan Fita, Maria Jose, Esteban, Emilio, Alonso-Gordoa, Teresa, Mellado Gonzalez, Begoña, Maroto, Pablo, Lázaro-Quintela, Martín, Cassinello-Espinosa, Javier, Pérez-Valderrama, Begoña, Garcias, Carmen, Castellano, Daniel

مصطلحات موضوعية: Abiraterone acetate, Combination, Docetaxel, Metastatic castration-resistant prostate cancer, Phase II, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Humans, Male, Prednisone, Prostatic Neoplasms, Castration-Resistant, Treatment Outcome

الوصف: We aimed to compare the efficacy and safety of maintaining or withdrawing abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer who had experienced cancer progression to this treatment and were beginning a docetaxel-based therapy. Phase II, randomised, open-label study conducted in patients with metastatic castration-resistant prostate cancer who were asymptomatic or mildly symptomatic. After open-label treatment with AAP, patients who had experienced cancer progression to AAP were randomised to 75 mg/m2 of docetaxel plus AAP or to receive 75 mg/m2 of docetaxel plus 10 mg of prednisone orally daily. The primary outcome was the radiographic progression-free survival rate at 12 months as evaluated by the investigators in all randomised patients. A total of 148 patients were included in open-label treatment with AAP, and of them, 94 patients were randomised to receive either docetaxel plus AAP (intervention group; n = 47) or docetaxel plus prednisone (control group; n = 47). The 12-month radiographic progression-free survival rates did not differ between the intervention group (34.9%; 95% CI 20.7-49.2) and the control group (33.9%; 95% CI 19.5-48.3). There were no significant differences in the time to radiographic progression and the overall survival between the intervention and control groups. Grade 3-5 neutropenia with the combination of docetaxel plus prednisone and AA was more frequent than with docetaxel plus prednisone (59.6% versus 27.7%). Our results indicate that the therapeutic strategy of maintaining AAP added to docetaxel in chemotherapy-naïve patients who have experienced cancer progression to AAP treatment should not be further evaluated and should be avoided in clinical practice. NCT02036060 https://clinicaltrials.gov/ct2/show/NCT02036060Test.

العلاقة: http://hdl.handle.net/10668/22179Test

الإتاحة: https://doi.org/10.1016/j.ejca.2022.08.002Test
http://hdl.handle.net/10668/22179Test

المؤلفون: Crespo, Guillermo, Jiménez-Fonseca, Paula, Custodio, Ana, López, Carlos, Carmona-Bayonas, Alberto, Alonso, Vicente, Navarro, Miguel, Aller, Javier, Sevilla, Isabel, Grande, Enrique, Gajate, Pablo, Alonso-Gordoa, Teresa, Matos, Ignacio, Capdevila, Jaume, Nieto, Beatriz, Barriuso, Jorge

المصدر: Crespo , G , Jiménez-Fonseca , P , Custodio , A , López , C , Carmona-Bayonas , A , Alonso , V , Navarro , M , Aller , J , Sevilla , I , Grande , E , Gajate , P , Alonso-Gordoa , T , Matos , I , Capdevila , J , Nieto , B & Barriuso , J 2017 , ' Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors : a Spanish multicenter experience ' , Future oncology (London, England) , vol. 13 , no. 7 , pp. 615-624 . https://doi.org/10.2217/fon-2016-0434Test

مصطلحات موضوعية: Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Capecitabine/administration & dosage, Dacarbazine/administration & dosage, Female, Humans, Male, Middle Aged, Neoplasm Grading, Neuroendocrine Tumors/diagnosis, Proportional Hazards Models, Spain, Survival Analysis, Treatment Outcome, ResearchInstitutes_Networks_Beacons/mcrc, Manchester Cancer Research Centre

الوصف: BACKGROUND & METHODS: Capecitabine and temozolomide chemotherapy was used in 65 patients with grade 1/2 neuroendocrine tumors (NETs). 46 patients (70.8%) had pancreatic NETs (pNETs). RESULTS: Response rate was 47.7%, with two complete responses (3.1%), 29 partial responses (44.6%) and 27 patients (41.5%) achieved stable disease. Median progression-free survival was 16.1 months (95% CI: 10.7-21.6) and overall survival was 38.3 months (95% CI: 24.6-51.9). Differences in progression-free survival and overall survival between pNETs and non-pNETs were not found. Nine (13.8%) patients experienced grade 3/4 toxicities, mainly thrombocytopenia (10.8%) and neutropenia (7.7%). CONCLUSION: This is the largest reported series of NETs treated with capecitabine and temozolomide in daily practice and shows that this combination is a promising treatment option for both grade 1/2 pNETs and non-pNETs.

الإتاحة: https://doi.org/10.2217/fon-2016-0434Test
https://research.manchester.ac.uk/en/publications/e5547d79-a6f7-4616-acd7-baba0bbe43c1Test