المؤلفون: Cortes, Javier, Winer, Eric, Lipatov, Oleg, Im, Seock-Ah, Gonçalves, Anthony, MUÑOZ COUSELO, EVA

المساهمون: Institut Català de la Salut, Cortes J Oncology Department, International Breast Cancer Center (BCC), Pangaea Oncology, Quirónsalud, Barcelona, Spain. Department of Medicine, Faculty of Biomedical and Health Sciences, European University of Madrid, Madrid, Spain. Winer EP Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. Lipatov O Department of Oncology, Republican Clinical Oncology Dispensary of the Ministry of Public Health of Bashkortostan Republic, Ufa, Russia. Im SA Department of Internal Medicine, Seoul National University Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea. Gonçalves A Aix Marseille University, CNRS, INSERM, Department of Medical Oncology, Institut Paoli-Calmettes, CRCM, Marseille, France. Muñoz-Couselo E Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: Scientia

مصطلحات موضوعية: Mama - Càncer - Tractament, Mama - Càncer - Aspectes genètics, Marcadors tumorals, Antígens, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms, Other subheadings::Other subheadings::Other subheadings::/drug therapy, CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::B7 Antigens::B7-H1 Antigen, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::péptidos y proteínas de señalización intercelular::antígenos B7::antígeno B7-H1

الوصف: Pembrolizumab; Triple‐negative breast cancer ; Pembrolizumab; Cáncer de mama triple negativo ; Pembrolizumab; Càncer de mama triple negatiu ; The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types.

وصف الملف: application/pdf

العلاقة: The Journal of Pathology: Clinical Research;10(3); https://doi.org/10.1002/2056-4538.12371Test; Cortes J, Winer EP, Lipatov O, Im SA, Gonçalves A, Muñoz-Couselo E, et al. Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119. J Pathol Clin Res. 2024 May;10(3):e12371.; https://hdl.handle.net/11351/11362Test

الإتاحة: https://doi.org/10.1002/2056-4538.12371Test
https://hdl.handle.net/11351/11362Test

المؤلفون: Cescon, David W, Schmid, Peter, Rugo, Hope S, Im, Seock-Ah, Yusof, Mastura Md., Gallardo, Carlos, Lipatov, Oleg, Barrios, Carlos H, Perez-Garcia, Jose, Iwata, Hiroji, Masuda, Norikazu, Otero, Marco Torregroza, Gokmen, Erhan, Loi, Sherene, Haiderali, Amin, Zhou, Xuan, Guo, Zifang, Nguyen, Allison Martin, Cortes, Javier

المصدر: JNCI: Journal of the National Cancer Institute; May2024, Vol. 116 Issue 5, p717-727, 11p

مصطلحات موضوعية: TRIPLE-negative breast cancer, QUALITY of life, PEMBROLIZUMAB, PHYSICAL mobility, HORMONE receptor positive breast cancer, CANCER chemotherapy

مستخلص: Background In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Methods Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30), Breast Cancer–Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Results Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = −1.81, 95% confidence interval [CI] = −6.92 to 3.30), emotional functioning (least-squares mean difference = −1.43, 95% CI = −7.03 to 4.16), physical functioning (least-squares mean difference = −1.05, 95% CI = −6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = −5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning. Conclusions Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10). [ABSTRACT FROM AUTHOR]

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المؤلفون: Slamon, Dennis J., Diéras, Véronique, Rugo, Hope S., Harbeck, Nadia, Im, Seock-Ah, Gelmon, Karen A., Lipatov, Oleg N., Walshe, Janice M., Martin, Miguel, Chavez-MacGregor, Mariana, Bananis, Eustratios, Gauthier, Eric, Lu, Dongrui R., Kim, Sindy, Finn, Richard S.

المصدر: Journal of Clinical Oncology; 3/20/2024, Vol. 42 Issue 9, p994-1000, 9p

المؤلفون: Cortes, Javier, Rugo, Hope S, Cescon, David W, Im, Seock-Ah, Yusof, Mastura M, Gallardo, Carlos, Lipatov, Oleg, Barrios, Carlos H, Perez-Garcia, Jose, Iwata, Hiroji, Masuda, Norikazu, Torregroza Otero, Marco, Gokmen, Erhan, Loi, Sherene, Guo, Zifang, Zhou, Xuan, Karantza, Vassiliki, Pan, Wilbur, Schmid, Peter, KEYNOTE-355 Investigators, Taylor, Donatienne

المساهمون: UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale

المصدر: The New England journal of medicine, Vol. 387, no.3, p. 217-226 (2022)

مصطلحات موضوعية: Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, B7-H1 Antigen, Humans, Immune Checkpoint Inhibitors, Triple Negative Breast Neoplasms

الوصف: In an interim analysis of this phase 3 trial, the addition of pembrolizumab to chemotherapy resulted in longer progression-free survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more. The results of the final analysis of overall survival have not been reported. We randomly assigned patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer in a 2:1 ratio to receive pembrolizumab (200 mg) every 3 weeks plus the investigator's choice of chemotherapy (nanoparticle albumin-bound paclitaxel, paclitaxel, or gemcitabine-carboplatin) or placebo plus chemotherapy. The primary end points were progression-free survival (reported previously) and overall survival among patients whose tumors expressed PD-L1 with a CPS of 10 or more (the CPS-10 subgroup), among patients whose tumors expressed PD-L1 with a CPS of 1 or more (the CPS-1 subgroup), and in the intention-to-treat population. Safety was also assessed. A total of 847 patients underwent randomization: 566 were assigned to the pembrolizumab-chemotherapy group, and 281 to the placebo-chemotherapy group. The median follow-up was 44.1 months. In the CPS-10 subgroup, the median overall survival was 23.0 months in the pembrolizumab-chemotherapy group and 16.1 months in the placebo-chemotherapy group (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = 0.0185 [criterion for significance met]); in the CPS-1 subgroup, the median overall survival was 17.6 and 16.0 months in the two groups, respectively (hazard ratio, 0.86; 95% CI, 0.72 to 1.04; two-sided P = 0.1125 [not significant]); and in the intention-to-treat population, the median overall survival was 17.2 and 15.5 months, respectively (hazard ratio, ...

العلاقة: boreal:280104; http://hdl.handle.net/2078.1/280104Test; info:pmid/35857659; urn:EISSN:1533-4406

الإتاحة: https://doi.org/10.1056/NEJMoa2202809Test
http://hdl.handle.net/2078.1/280104Test

المؤلفون: Li, Rubi K., Tokunaga, Eriko, Adamchuk, Hryhoriy, Vladimirov, Vladimir, Yanez, Eduardo, Lee, Keun Seok, Bondarenko, Igor, Vana, Alicia, Hilton, Fiona, Ishikawa, Tomofumi, Tajima, Kentaro, Lipatov, Oleg

المساهمون: Pfizer

المصدر: BioDrugs ; volume 36, issue 1, page 55-69 ; ISSN 1173-8804 1179-190X

مصطلحات موضوعية: Pharmacology (medical), Pharmacology, General Medicine, Biotechnology

الإتاحة: https://doi.org/10.1007/s40259-021-00513-7Test

المؤلفون: Cortes, Javier, Cescon, David W, Rugo, Hope S, Nowecki, Zbigniew, Im, Seock-Ah, Yusof, Mastura Md, Gallardo, Carlos, Lipatov, Oleg, Barrios, Carlos H, Holgado, Esther, Iwata, Hiroji, Masuda, Norikazu, Otero, Marco Torregroza, Gokmen, Erhan, Loi, Sherene, Guo, Zifang, Zhao, Jing, Aktan, Gursel, Karantza, Vassiliki, Schmid, Peter, KEYNOTE-355 Investigators, Taylor, Donatienne

المساهمون: UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale

المصدر: Lancet (London, England), Vol. 396, no.10265, p. 1817-1828 (2020)

مصطلحات موضوعية: Adult, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, B7-H1 Antigen, Double-Blind Method, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Recurrence, Local, Outcome Assessment, Health Care, Placebos, Progression-Free Survival, Triple Negative Breast Neoplasms

الوصف: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer. In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine-carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at ...

العلاقة: boreal:280105; http://hdl.handle.net/2078.1/280105Test; info:pmid/33278935; urn:EISSN:1474-547X

الإتاحة: https://doi.org/10.1016/S0140-6736Test(20)32531-9
http://hdl.handle.net/2078.1/280105Test

المؤلفون: Schmid, Peter, Lipatov, Oleg, Im, Seock-Ah, Goncalves, Anthony, Muñoz-Couselo, Eva, Lee, Keun Seok, Tamura, Kenji, Testa, Laura, Witzel, Isabell, Ohtani, Shoichiro, Turner, Nicholas, Zambelli, Stefania, Harbeck, Nadia, Andre, Fabrice, Dent, Rebecca, Mejia, Jaime A, Zhou, Xuan, Haiderali, Amin, Nguyen, Allison Martin, Cortes, Javier, Winer, Eric P

المصدر: Schmid, Peter; Lipatov, Oleg; Im, Seock-Ah; Goncalves, Anthony; Muñoz-Couselo, Eva; Lee, Keun Seok; Tamura, Kenji; Testa, Laura; Witzel, Isabell; Ohtani, Shoichiro; Turner, Nicholas; Zambelli, Stefania; Harbeck, Nadia; Andre, Fabrice; Dent, Rebecca; Mejia, Jaime A; Zhou, Xuan; Haiderali, Amin; Nguyen, Allison Martin; Cortes, Javier; Winer, Eric P (2023). Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study. European Journal of Cancer, 195:113393.

مصطلحات موضوعية: Clinic for Gynecology, 610 Medicine & health, Cancer Research, Oncology, Chemotherapy, Health-related quality of life, Patient-reported outcomes, Pembrolizumab, Triple-negative breast cancer

الوصف: Background: In KEYNOTE-119 (ClinicalTrials.gov, NCT02555657), overall survival (primary end-point) was similar between pembrolizumab and chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC), although the pembrolizumab treatment effect increased with tumour PD-L1 expression. We report results of prespecified health-related quality of life (HRQoL) analyses from KEYNOTE-119. Methods: Eligible patients were randomised 1:1 to pembrolizumab 200 mg Q3W intravenously for up to 35 cycles or treatment of physician's choice per local/country guidelines. Prespecified exploratory end-points were the change from baseline in HRQoL (EORTC QLQ-C30, QLQ-BR23) and to characterise utilities (EQ-5D-3L). Time to deterioration (TTD) was the time from start of treatment to first onset of a ≥10-point worsening from baseline. Results: HRQoL analyses included 187 patients with tumour PD-L1 combined positive score (CPS) ≥10. Changes from baseline at 6 weeks (primary analysis time point) were directionally better with pembrolizumab versus chemotherapy for QLQ-C30 GHS/QoL (between-group difference in least-squares mean scores of 4.21 [95% CI, -1.38 to 9.80]), QLQ-C30 functional scales (physical, role, cognitive, social), QLQ-C30 symptom scales/items (fatigue, nausea/vomiting, dyspnoea, appetite loss), and QLQ-BR23 symptom scales/items (systemic therapy side-effects, upset by hair loss). Median TTD was directionally longer for pembrolizumab versus chemotherapy for QLQ-C30 QHS/QoL (4.3 versus 1.7 months), QLQ-C30 nausea/vomiting (7.7 versus 4.8 months), and QLQ-BR23 systemic therapy side-effects (6.1 versus 3.4 months). Minimal treatment differences were observed for other HRQoL end-points. Conclusions: HRQoL results were consistent with clinical outcomes and appeared to be driven by results for patients with tumour PD-L1 CPS ≥10.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/256039/1/ZORA_256039.pdfTest; info:pmid/37976633; urn:issn:0959-8049

الإتاحة: https://doi.org/10.5167/uzh-25603910.1016/j.ejca.2023.113393Test
https://www.zora.uzh.ch/id/eprint/256039Test/
https://www.zora.uzh.ch/id/eprint/256039/1/ZORA_256039.pdfTest

المؤلفون: Cescon, David W, Schmid, Peter, Rugo, Hope S, Im, Seock-Ah, Md. Yusof, Mastura, Gallardo, Carlos, Lipatov, Oleg, Barrios, Carlos H, Perez-Garcia, Jose, Iwata, Hiroji, Masuda, Norikazu, Otero, Marco Torregroza, Gokmen, Erhan, Loi, Sherene, Haiderali, Amin, Zhou, Xuan, Guo, Zifang, Nguyen, Allison Martin, Cortes, Javier

المساهمون: Merck Sharp & Dohme LLC, Merck & Co., Inc.

المصدر: JNCI: Journal of the National Cancer Institute ; volume 116, issue 5, page 717-727 ; ISSN 0027-8874 1460-2105

الوصف: Background In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Methods Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator’s choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30), Breast Cancer–Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Results Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = −1.81, 95% confidence interval [CI] = −6.92 to 3.30), emotional functioning (least-squares mean difference = −1.43, 95% CI = −7.03 to 4.16), physical functioning (least-squares mean difference = −1.05, 95% CI = −6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = ...

الإتاحة: https://doi.org/10.1093/jnci/djad240Test
https://academic.oup.com/jnci/article-pdf/116/5/717/57420884/djad240.pdfTest

المؤلفون: Candelaria, Myrna, González, Derlis E., Delamain, Marcia Torresan, Bär, Daniel Oscar, Beniwal, Surender Kumar, Dasappa, Lokanatha, Flores, David Hugo, Querol, John, Guan, Toh See, Lipatov, Oleg Nikolaevich, Volodicheva, Elena Mikhailovna, Patel, Moosa, Safaee Nodehi, Sayyed Reza, Fogliatto, Laura, Paravisini, Alexandra, Perez Diaz, Luis

المساهمون: mAbxience Research S.L

المصدر: Leukemia & Lymphoma ; volume 60, issue 14, page 3375-3385 ; ISSN 1042-8194 1029-2403

الإتاحة: https://doi.org/10.1080/10428194.2019.1633632Test

المؤلفون: Molina, Ana M., Hutson, Thomas E., Nosov, Dmitry, Tomczak, Piotr, Lipatov, Oleg, Sternberg, Cora N., Motzer, Robert, Eisen, Tim

المساهمون: AVEO Oncology and Astellas Pharma US, Inc

المصدر: European Journal of Cancer ; volume 94, page 87-94 ; ISSN 0959-8049

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.ejca.2018.02.009Test
https://api.elsevier.com/content/article/PII:S0959804918301783?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0959804918301783?httpAccept=text/plainTest