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1. Ulcerative colitis six years after colon cancer: only a coincidence?

Author

Sakellakis M, Makatsoris T, Gkermpesi M, Peroukidis S, and Kalofonos H

Subjects
Medicine (General), R5-920
Abstract

Minas Sakellakis,1 Thomas Makatsoris,1 Maria Gkermpesi,2 Stavros Peroukidis,1 Haralabos Kalofonos11Division of Oncology, Department of Medicine, 2Department of Pathology, University, Hospital of Patras, Patras, GreeceAbstract: The association between inflammatory bowel disease and colorectal cancer is well known. Ulcerative colitis is a risk factor for the development of colorectal cancer, and this risk increases with the activity and duration of bowel inflammation. Here we describe the case of a 52-year-old man who developed ulcerative colitis 6 years after the diagnosis and treatment of colon cancer. Although this could be a coincidence, there could be additional possibilities, like pre-existence of quiescent colitis, late effect of therapy, or maybe the existence of common pathogenetic factors contributing to the development of ulcerative colitis and colorectal cancer.Keywords: ulcerative, colitis, colorectal, cancer, inflammation

Published
2014

2. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Author

Bachelot, T., Bouzid, K., Campone, M., Desmoulins, I., Coudert, B., Bondarenko, I., Nowecki, Z., Glogowska, I., Ciruelos Gil, E., Errihani, H., Dalenc, F., Ricci, F., Dieras, V., Kaufman, B., Paluch-Shimon, S., Wardley, A., Schneeweiss, A., Ferreira, A., Mano, M., Kalofonos, H., Andreetta, C., Puglisi, F., Montemurro, F., Barrett, S., Zhang, Q., Mavroudis, D., Matus, J., Villarreal Garza, C., Beato, C., Ismael, G., Hu, X., Abdel Azeem, H., Gaafar, R., Perrin, C., Kerbrat, P., Ettl, J., Paepke, S., Hitre, E., Lang, I., Trudeau, M., Verma, S., Li, H., Hoffmann, O., Aktas, B., Cariello, A., Cruciani, G., Tienghi, A., Tondini, C., Al-Twegieri, T., Loman, N., Laing, R., Miles, D., Brain, E., Fasching, P., Lux, M., Frassoldati, A., Aziz, Z., Salas, J., Streb, J., Krzemieniecki, K., Wronski, A., Garcia Garcia, J., Menjon Beltran, S., Cicin, I., Schmid, P., Gallagher, C., Turner, N., Tong, Z., Boer, K., Juhász, B., Horvath, Z., Bianchini, G., Gianni, L., Curigliano, G., Juarez Ramiro, A., Susnjar, S., Matos, E., Sevillano, E., Garcia Estevez, L., Gokmen, E., Uslu, R., Wildiers, H., Schutz, F., Cruz, M., Bourgeois, H., von Schumann, R., Stemmer, S., Dominguez, A., Morales-Vásques, F., Wojtukiewicz, M., Trifunovic, J., Echarri Gonzalez, M.J., Illarramendi Mañas, J., Martinez De Dueñas, E., Voitko, N., Hicks, J., Waters, S., Barrett-Lee, P., Wheatley, D., De Boer, R., Cocquyt, V., Jerusalem, G., Barrios, C., Panasci, L., Mattson, J., Tanner, M., Gozy, M., Vasilopoulos, G., Papandreou, C., Revesz, J., Battelli, N., Benedetti, G., Latini, L., Gridelli, C., Lazaro Leon, J., Alarcón Company, J., Arance Fernandez, A., Barnadas Molins, A., Calvo Plaza, I., Bratos, R., Gonzalez Martin, A., Izarzugaza Peron, Y., Klint, L., Kovalev, A., McCarthy, N., Yeo, B., Kee, D., Thomson, J., White, S., Greil, R., Wang, S., Artignan, X., Juhasz-Böess, I., Rody, A., Ngan, R., Dourleshter, F., Goldberg, H., Doni, L., Di Costanzo, F., Ferraù, F., Drobniene, M., Aleknavicius, E., Rashid, K., Costa, L., de la Cruz Merino, L., Garcia Saenz, J., López, R., Del Val Munoz, O., Ozyilkan, O., Azribi, F., Jaafar, H., Baird, R., Verrill, M., Beith, J., Petzer, A., Moreira de Andrade, J., Bernstein, V., Macpherson, N., Rayson, D., Saad Eldin, I., Achille, M., Augereau, P., Müller, V., Rasco, A., Evron, E., Katz, D., Berardi, R., Cascinu, S., De Censi, A., Gennari, A., El-Saghir, N., Ghosn, M., Oosterkamp, H.M., Van den Bosch, J., Kukulska, M., Kalinka, E., Alonso, J., Dalmau Portulas, E., Del Mar Gordon Santiago, M., Pelaez Fernandez, I., Aksoy, S., Altundag, K., Senol Coskun, H., Bozcuk, H., Shparyk, Y., Barraclough, L., Levitt, N., Panwar, U., Kelly, S., Rigg, A., Varughese, M., Castillo, C., Fein, L., Malik, L., Stuart-Harris, R., Singer, C., Stoeger, H., Samonigg, H., Feng, J., Cedeño, M., Ruohola, J., Berdah, J.-F., Goncalves, A., Orfeuvre, H., Grischke, E.-M., Simon, E., Wagner, S., Koumakis, G., Papazisis, K., Ben Baruch, N., Fried, G., Geffen, D., Karminsky, N., Peretz, T., Cavanna, L., Pedrazzioli, P., Grasso, D., Ruggeri, E., D’Auria, G., Moscetti, L., Juozaityte, E., Rodriguez Cid, J., Roerdink, H., Siddiqi, N., Passos Coelho, J., Arcediano Del Amo, A., Garcia Garre, E., García Gonzalez, M., Garcia-Palomo Perez, A., Herenandez Perez, C., Lopez Alvarez, P., Lopez De Ceballos, M.H., Martínez Jañez, N., Mele Olive, M., McAdam, K., Perren, T., Dunn, G., Humphreys, A., Taylor, W., Vera, R., Kaen, L., Andel, J., Steger, G., De Grève, J., Huizing, M., Hegg, R., Joy, A., Kuruvilla, P., Sehdev, S., Smiljanic, S., Kütner, R., Alexandre, J., Grosjean, J., Laplaige, P., Largillier, R., Maes, P., Martin, P., Pottier, V., Christensen, B., Khandan, F., Lück, H.-J., Zahm, D.-M., Fountzilas, G., Karavasilis, V., Safra, T., Inbar, M., Ryvo, L., Bonetti, A., Seles, E., Giacobino, A., Chavarri Guerra, Y., de Jongh, F., van der Velden, A., van Warmerdam, L., Vrijaldenhoven, S., Smorenburg, C.H., Cavero, M., Andres Conejero, R., Oltra Ferrando, A., Redondo Sanchez, A., Ribelles Entrena, N., Saura Grau, S., Viñas Vilaro, G., Bachmeier, K., Beresford, M., Butt, M., Joffe, J., Poole, C., Woodings, P., Chakraborti, P., Yordi, G., Woodward, N., Nobre, A., Luiz Amorim, G., Califaretti, N., Fox, S., Robidoux, A., Li, E., Li, N., Jiang, J., Soria, T., Padrik, P., Lahdenpera, O., Barletta, H., Dohollou, N., Genet, D., Prulhiere, K., Coeffic, D., Facchini, T., Vieillot, S., Catala, S., Teixeira, L., Hesse, T., Kühn, T., Ober, A., Repp, R., Schröder, W., Pectasides, D., Bodoky, G., Kahan, Z., Jiveliouk, I., Rosengarten, O., Rossi, V., Alabiso, O., Pérez Martínez, M., van de Wouw, A.J., Smok-Kalwat, J., Damasecno, M., Augusto, I., Sousa, G., Saadein, A., Abdelhafiez, N., Abulkhair, O., Antón Torres, A., Corbellas Aparicio, M., Llorente Domenech, R., Florián Jerico, J., Garcia Mata, J., Gil Raga, M., Galan Brotons, A., Llombart Cussac, A., Llorca Ferrandiz, C., Martinez Del Prado, P., Olier Garate, C., Rodriguez Sanchez, C., Sanchez Gomez, R., Santisteban Eslava, M., Soberino, J., Vidal Losada Garcia, M., Soto de Prado, D., Torrego Garcia, J., Vicente Rubio, E., Garcia, M., Murias Rosales, A., Granstam Björneklett, H., Narbe, U., Jafri, M., Rea, D., Newby, J., Jones, A., Westwell, S., Ring, A., Alonso, I., Rodríguez, R., Ciruelos, E., Peretz-Yablonski, T., Merot, J.-L., Trask, P., du Toit, Y., Pena-Murillo, C., Revelant, V., and Klingbiel, D.

Published
2021
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3. Serum neurofilament light chain levels as biomarker of paclitaxel-induced cognitive impairment in patients with breast cancer: a prospective study

Author

Argyriou, A, Karteri, S, Bruna, J, Mariotto, S, Simo, M, Velissaris, D, Kalofonou, F, Cavaletti, G, Ferrari, S, Kalofonos, H, Argyriou A. A., Karteri S., Bruna J., Mariotto S., Simo M., Velissaris D., Kalofonou F., Cavaletti G., Ferrari S., Kalofonos H. P., Argyriou, A, Karteri, S, Bruna, J, Mariotto, S, Simo, M, Velissaris, D, Kalofonou, F, Cavaletti, G, Ferrari, S, Kalofonos, H, Argyriou A. A., Karteri S., Bruna J., Mariotto S., Simo M., Velissaris D., Kalofonou F., Cavaletti G., Ferrari S., and Kalofonos H. P.

Abstract

Objective: To prospectively assess the utility of serum neurofilament light chain (sNfL) levels in identifying the risk to develop chemotherapy-induced cognitive impairment (CICI) in cancer patients. We also examined if sNfL can be identified as an early biomarker of CICI development. Methods: We longitudinally measured sNfL levels in 20 female patients with breast cancer, scheduled to receive the 12 weekly paclitaxel-based regimen. An equal number of age-matched female heathy subjects was incuded as control group. CICI was graded by means of the Montreal Cognitive Assessment scale (MOCA); peripheral neurotoxicity (PN) was graded using the neurosensory Common Criteria for Adverse Events (CTCAE)v5.0, while sNfL levels were quantified using a high-sensitive technique (Quanterix, Simoa) before the administration of chemotherapy (T0), after 3 courses (T1), and at the end of chemotherapy (T2). Results: Pre-treatment sNfL levels were comparable in patients and controls (p = 0.103). At T2, 5/20 patients (mean age 61.4 ± 5.0 years) developed CICI. These 5 patients also had clinically-significant PN. Patients with and without CICI had comparable sNfL values at T2 (p = 0.1). In addition, at T2, sNfL levels did not correlate significantly with MOCA score in CICI patients (p = 0.604). The difference of sNfL levels between T1 and T0 failed to predict independently the occurrence of CICI at T2. Conclusion: Our findings do not support the utility of measuring sNfL levels as a biomarker of CICI. Grade 2–3 PN most strongly confounded our outcomes. Considering the small sample size, which might have prevented the results from being extrapolated, further testing in larger studies is warranted.

Published
2022

4. Evaluation of the psychometric properties of the EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20)

Author

Kieffer, Jacobien M., Postma, Tjeerd J., van de Poll-Franse, Lonneke, Mols, Floortje, Heimans, Jan J., Cavaletti, Guido, Aaronson, Neil K., Cavaletti, G., Cornblath, D. R., Merkies, I. S. J., Postma, T. J., Valsecchi, M. G., Galimberti, S., Rossi, E., Cavaletti, G., Frigeni, B., Lanzani, F., Mattavelli, L., Piatti, M. L., Alberti, P., Binda, D., Bidoli, P., Cazzaniga, M., Cortinovis, D., Bruna, J., Velasco, R., Argyriou, A. A., Kalofonos, H. P., Psimaras, D., Ricard, D., Pace, A., Galiè, E., Briani, C., Lucchetta, M., Campagnolo, M., Torre, C. Dalla, Faber, C. G., Merkies, I. S. J., Vanhoutte, E. K., Bakkers, M., Brouwer, B., Boogerd, M., Lalisang, R. I., Boogerd, W., Brandsma, D., Koeppen, S., Hense, J., Grant, R., Storey, D., Kerrigan, S., Schenone, A., Reni, L., Piras, B., Fabbri, S., Pessino, A., Padua, L., Granata, G., Leandri, M., Ghignotti, I., Plasmati, R., Pastorelli, F., Postma, T. J., Heimans, J. J., Eurelings, M., Meijer, R. J., Grisold, W., Pozza, E. Lindeck, Mazzeo, A., Toscano, A., Russo, M., Tomasello, C., Altavilla, G., Prado, M. Penas, Gonzalez, C. Dominguez, Dorsey, S. G., and In Collaboration with the CI-PeriNomS Group

Published
2017
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6. Prospectively Assessing Serum Neurofilament Light Chain Levels As A Biomarker Of Paclitaxel-Induced Peripheral Neurotoxicity In Breast Cancer Patients

Author

Karteri, S, Bruna, J, Argyriou, A, Mariotto, S, Velasco, R, Alemany, M, Kalofonou, F, Alberti, P, Dinoto, A, Velissaris, D, Stradella, A, Cavaletti, G, Ferrari, S, Kalofonos, H, Argyriou, AA., Kalofonos, HP, Karteri, S, Bruna, J, Argyriou, A, Mariotto, S, Velasco, R, Alemany, M, Kalofonou, F, Alberti, P, Dinoto, A, Velissaris, D, Stradella, A, Cavaletti, G, Ferrari, S, Kalofonos, H, Argyriou, AA., and Kalofonos, HP

Abstract

Our aim was to assess the significance of measuring serum neurofilament light chain (sNfL) levels as a biomarker of paclitaxel-induced peripheral neurotoxicity (PIPN). We longitudinally measured sNfL in breast cancer patients, scheduled to receive the 12-weekly paclitaxel-based regimen. Patients were clinically examined by means of the Total Neuropathy Score-clinical version (TNSc), while sNfL were quantified, using the highly sensitive Simoa technique, before starting chemotherapy (baseline), after 2 (week 2) and 3 (week 3) weekly courses, and at the end of chemotherapy (week 12). Among 59 included patients (mean age: 53.1 ± 11.5 years), 33 (56%) developed grade 0-1 and 26 (44%) grade 2-3 PIPN at week 12. A significant longitudinal increase of sNfL levels from baseline to week-12 was determined, whereas patients with TNSc grade 2-3 PIPN had significantly increased sNfL levels at week 12, compared to those with grade 0-1. receiver-operated characteristics (ROC) analysis defined a value of NfL of >85 pg/mL at week 3 as the best discriminative determination to predict the development of grade 2-3 PIPN at week 12 (sensitivity 46.2%, specificity 84.8%). The logistic binary regression analysis revealed that age > 50 years and the cutoff of >85 pg/mL of sNfL levels at week 3 independently predicted the development of grade 2-3 PIPN at week 12 with a sensitivity of 46%, a specificity of 91%, and a positive and negative predictive values of 75% and 67%, respectively. sNfL levels seem to be a valuable biomarker of neuro-axonal injury in PIPN. An early increase of this biomarker after a 3-weekly chemotherapy course can be a predictive marker of final PIPN severity.

Published
2022

8. Patients' and physicians' interpretation of chemotherapy-induced peripheral neurotoxicity

Author

Cavaletti, G., Cornblath, D. R., Merkies, I. S. J., Postma, T. J., Rossi, E., Alberti, Paola, Bruna, J., Argyriou, A. A., Briani, C., Velasco, Riccardo, Kalofonos, H. P., Psimaras, D., Ricard, D., Pace, A., Faber, C. G., Lalisang, R. I., Brandsma, D., Koeppen, S., Kerrigan, S., Schenone, A., Grisold, W., Mazzeo, A., Padua, L., Dorsey, S. G., Penas-Prado, M., Valsecchi, M. G., Frigeni, B., Lanzani, F., Mattavelli, L., Piatti, M. L., Binda, D., Bidoli, P., Cazzaniga, M., Cortinovis, D., Galie, E., Campagnolo, M., Salvalaggio, A., Ruiz, M., Vanhoutte, E. K., Boogerd, W., Hense, J., Grant, R., Storey, D., Reni, L., Demichelis, C., Pessino, A., Granata, G., Leandri, Martina, Ghigliotti, I., Plasmati, R., Pastorelli, Federica, Heimans, J. J., Eurelings, M., Meijer, R. J., Pozza, E. L., Toscano, A., Gentile, L., Santarpia, M., Gonzalez, C. D., Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: DA KG Polikliniek (9), Cavaletti, G, Cornblath, D, Merkies, I, Postma, T, Rossi, E, Alberti, P, Bruna, J, Argyriou, A, Briani, C, Velasco, R, Kalofonos, H, Psimaras, D, Ricard, D, Pace, A, Faber, C, Lalisang, R, Brandsma, D, Koeppen, S, Kerrigan, S, Schenone, A, Grisold, W, Mazzeo, A, Padua, L, Dorsey, S, Penas-Prado, M, Valsecchi, M, Bidoli, P, Cazzaniga, M, Neurology, and CCA - Cancer Treatment and quality of life

Subjects
Adult, medicine.medical_specialty, Activities of daily living, side effect, media_common.quotation_subject, medicine.medical_treatment, assessment, chemotherapy, neurotoxicity, patient reported outcome measures, side effects, Medizin, NEUROPATHY CIPN, Neurological examination, Severity of Illness Index, 03 medical and health sciences, Vibration perception, 0302 clinical medicine, Perception, Internal medicine, Activities of Daily Living, medicine, Humans, VALIDITY, media_common, Oncologists, Neuroscience (all), Neurology (clinical), Chemotherapy, medicine.diagnostic_test, business.industry, General Neuroscience, Neurotoxicity, Outcome measures, Peripheral Nervous System Diseases, assessment, chemotherapy, neurotoxicity, patient reported outcome measures, side effects, Adult, Humans, Neurotoxicity Syndromes, Peripheral Nervous System Diseases, Activities of Daily Living, Oncologists, Patient Reported Outcome Measures, Severity of Illness Index, OUTCOME MEASURES, medicine.disease, Peripheral, patient reported outcome measure, 030220 oncology & carcinogenesis, Neurotoxicity Syndromes, business, 030217 neurology & neurosurgery
Abstract

To test if and how chemotherapy-induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI-PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation ("impossible") generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%-65% of patients; 76%-78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%-56% of them. In Group 3 strength reduction was observed in 49%-50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.

Published
2019
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11. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Author

Miles, D., primary, Ciruelos, E., additional, Schneeweiss, A., additional, Puglisi, F., additional, Peretz-Yablonski, T., additional, Campone, M., additional, Bondarenko, I., additional, Nowecki, Z., additional, Errihani, H., additional, Paluch-Shimon, S., additional, Wardley, A., additional, Merot, J.-L., additional, Trask, P., additional, du Toit, Y., additional, Pena-Murillo, C., additional, Revelant, V., additional, Klingbiel, D., additional, Bachelot, T., additional, Bouzid, K., additional, Desmoulins, I., additional, Coudert, B., additional, Glogowska, I., additional, Ciruelos Gil, E., additional, Dalenc, F., additional, Ricci, F., additional, Dieras, V., additional, Kaufman, B., additional, Ferreira, A., additional, Mano, M., additional, Kalofonos, H., additional, Andreetta, C., additional, Montemurro, F., additional, Barrett, S., additional, Zhang, Q., additional, Mavroudis, D., additional, Matus, J., additional, Villarreal Garza, C., additional, Beato, C., additional, Ismael, G., additional, Hu, X., additional, Abdel Azeem, H., additional, Gaafar, R., additional, Perrin, C., additional, Kerbrat, P., additional, Ettl, J., additional, Paepke, S., additional, Hitre, E., additional, Lang, I., additional, Trudeau, M., additional, Verma, S., additional, Li, H., additional, Hoffmann, O., additional, Aktas, B., additional, Cariello, A., additional, Cruciani, G., additional, Tienghi, A., additional, Tondini, C., additional, Al-Twegieri, T., additional, Loman, N., additional, Laing, R., additional, Miles, D., additional, Brain, E., additional, Fasching, P., additional, Lux, M., additional, Frassoldati, A., additional, Aziz, Z., additional, Salas, J., additional, Streb, J., additional, Krzemieniecki, K., additional, Wronski, A., additional, Garcia Garcia, J., additional, Menjon Beltran, S., additional, Cicin, I., additional, Schmid, P., additional, Gallagher, C., additional, Turner, N., additional, Tong, Z., additional, Boer, K., additional, Juhász, B., additional, Horvath, Z., additional, Bianchini, G., additional, Gianni, L., additional, Curigliano, G., additional, Juarez Ramiro, A., additional, Susnjar, S., additional, Matos, E., additional, Sevillano, E., additional, Garcia Estevez, L., additional, Gokmen, E., additional, Uslu, R., additional, Wildiers, H., additional, Schutz, F., additional, Cruz, M., additional, Bourgeois, H., additional, von Schumann, R., additional, Stemmer, S., additional, Dominguez, A., additional, Morales-Vásques, F., additional, Wojtukiewicz, M., additional, Trifunovic, J., additional, Echarri Gonzalez, M.J., additional, Illarramendi Mañas, J., additional, Martinez De Dueñas, E., additional, Voitko, N., additional, Hicks, J., additional, Waters, S., additional, Barrett-Lee, P., additional, Wheatley, D., additional, De Boer, R., additional, Cocquyt, V., additional, Jerusalem, G., additional, Barrios, C., additional, Panasci, L., additional, Mattson, J., additional, Tanner, M., additional, Gozy, M., additional, Vasilopoulos, G., additional, Papandreou, C., additional, Revesz, J., additional, Battelli, N., additional, Benedetti, G., additional, Latini, L., additional, Gridelli, C., additional, Lazaro Leon, J., additional, Alarcón Company, J., additional, Arance Fernandez, A., additional, Barnadas Molins, A., additional, Calvo Plaza, I., additional, Bratos, R., additional, Gonzalez Martin, A., additional, Izarzugaza Peron, Y., additional, Klint, L., additional, Kovalev, A., additional, McCarthy, N., additional, Yeo, B., additional, Kee, D., additional, Thomson, J., additional, White, S., additional, Greil, R., additional, Wang, S., additional, Artignan, X., additional, Juhasz-Böess, I., additional, Rody, A., additional, Ngan, R., additional, Dourleshter, F., additional, Goldberg, H., additional, Doni, L., additional, Di Costanzo, F., additional, Ferraù, F., additional, Drobniene, M., additional, Aleknavicius, E., additional, Rashid, K., additional, Costa, L., additional, de la Cruz Merino, L., additional, Garcia Saenz, J., additional, López, R., additional, Del Val Munoz, O., additional, Ozyilkan, O., additional, Azribi, F., additional, Jaafar, H., additional, Baird, R., additional, Verrill, M., additional, Beith, J., additional, Petzer, A., additional, Moreira de Andrade, J., additional, Bernstein, V., additional, Macpherson, N., additional, Rayson, D., additional, Saad Eldin, I., additional, Achille, M., additional, Augereau, P., additional, Müller, V., additional, Rasco, A., additional, Evron, E., additional, Katz, D., additional, Berardi, R., additional, Cascinu, S., additional, De Censi, A., additional, Gennari, A., additional, El-Saghir, N., additional, Ghosn, M., additional, Oosterkamp, H.M., additional, Van den Bosch, J., additional, Kukulska, M., additional, Kalinka, E., additional, Alonso, J., additional, Dalmau Portulas, E., additional, Del Mar Gordon Santiago, M., additional, Pelaez Fernandez, I., additional, Aksoy, S., additional, Altundag, K., additional, Senol Coskun, H., additional, Bozcuk, H., additional, Shparyk, Y., additional, Barraclough, L., additional, Levitt, N., additional, Panwar, U., additional, Kelly, S., additional, Rigg, A., additional, Varughese, M., additional, Castillo, C., additional, Fein, L., additional, Malik, L., additional, Stuart-Harris, R., additional, Singer, C., additional, Stoeger, H., additional, Samonigg, H., additional, Feng, J., additional, Cedeño, M., additional, Ruohola, J., additional, Berdah, J.-F., additional, Goncalves, A., additional, Orfeuvre, H., additional, Grischke, E.-M., additional, Simon, E., additional, Wagner, S., additional, Koumakis, G., additional, Papazisis, K., additional, Ben Baruch, N., additional, Fried, G., additional, Geffen, D., additional, Karminsky, N., additional, Peretz, T., additional, Cavanna, L., additional, Pedrazzioli, P., additional, Grasso, D., additional, Ruggeri, E., additional, D’Auria, G., additional, Moscetti, L., additional, Juozaityte, E., additional, Rodriguez Cid, J., additional, Roerdink, H., additional, Siddiqi, N., additional, Passos Coelho, J., additional, Arcediano Del Amo, A., additional, Garcia Garre, E., additional, García Gonzalez, M., additional, Garcia-Palomo Perez, A., additional, Herenandez Perez, C., additional, Lopez Alvarez, P., additional, Lopez De Ceballos, M.H., additional, Martínez Jañez, N., additional, Mele Olive, M., additional, McAdam, K., additional, Perren, T., additional, Dunn, G., additional, Humphreys, A., additional, Taylor, W., additional, Vera, R., additional, Kaen, L., additional, Andel, J., additional, Steger, G., additional, De Grève, J., additional, Huizing, M., additional, Hegg, R., additional, Joy, A., additional, Kuruvilla, P., additional, Sehdev, S., additional, Smiljanic, S., additional, Kütner, R., additional, Alexandre, J., additional, Grosjean, J., additional, Laplaige, P., additional, Largillier, R., additional, Maes, P., additional, Martin, P., additional, Pottier, V., additional, Christensen, B., additional, Khandan, F., additional, Lück, H.-J., additional, Zahm, D.-M., additional, Fountzilas, G., additional, Karavasilis, V., additional, Safra, T., additional, Inbar, M., additional, Ryvo, L., additional, Bonetti, A., additional, Seles, E., additional, Giacobino, A., additional, Chavarri Guerra, Y., additional, de Jongh, F., additional, van der Velden, A., additional, van Warmerdam, L., additional, Vrijaldenhoven, S., additional, Smorenburg, C.H., additional, Cavero, M., additional, Andres Conejero, R., additional, Oltra Ferrando, A., additional, Redondo Sanchez, A., additional, Ribelles Entrena, N., additional, Saura Grau, S., additional, Viñas Vilaro, G., additional, Bachmeier, K., additional, Beresford, M., additional, Butt, M., additional, Joffe, J., additional, Poole, C., additional, Woodings, P., additional, Chakraborti, P., additional, Yordi, G., additional, Woodward, N., additional, Nobre, A., additional, Luiz Amorim, G., additional, Califaretti, N., additional, Fox, S., additional, Robidoux, A., additional, Li, E., additional, Li, N., additional, Jiang, J., additional, Soria, T., additional, Padrik, P., additional, Lahdenpera, O., additional, Barletta, H., additional, Dohollou, N., additional, Genet, D., additional, Prulhiere, K., additional, Coeffic, D., additional, Facchini, T., additional, Vieillot, S., additional, Catala, S., additional, Teixeira, L., additional, Hesse, T., additional, Kühn, T., additional, Ober, A., additional, Repp, R., additional, Schröder, W., additional, Pectasides, D., additional, Bodoky, G., additional, Kahan, Z., additional, Jiveliouk, I., additional, Rosengarten, O., additional, Rossi, V., additional, Alabiso, O., additional, Pérez Martínez, M., additional, van de Wouw, A.J., additional, Smok-Kalwat, J., additional, Damasecno, M., additional, Augusto, I., additional, Sousa, G., additional, Saadein, A., additional, Abdelhafiez, N., additional, Abulkhair, O., additional, Antón Torres, A., additional, Corbellas Aparicio, M., additional, Llorente Domenech, R., additional, Florián Jerico, J., additional, Garcia Mata, J., additional, Gil Raga, M., additional, Galan Brotons, A., additional, Llombart Cussac, A., additional, Llorca Ferrandiz, C., additional, Martinez Del Prado, P., additional, Olier Garate, C., additional, Rodriguez Sanchez, C., additional, Sanchez Gomez, R., additional, Santisteban Eslava, M., additional, Soberino, J., additional, Vidal Losada Garcia, M., additional, Soto de Prado, D., additional, Torrego Garcia, J., additional, Vicente Rubio, E., additional, Garcia, M., additional, Murias Rosales, A., additional, Granstam Björneklett, H., additional, Narbe, U., additional, Jafri, M., additional, Rea, D., additional, Newby, J., additional, Jones, A., additional, Westwell, S., additional, Ring, A., additional, Alonso, I., additional, and Rodríguez, R., additional

Published
2021
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15. Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy Induced Peripheral Neurotoxicity

Author

Alberti, P, Bernasconi, D, Cornblath, D, Jose Merkies, I, Park, S, Velasco, R, Bruna, J, Psimaras, D, Susanne, K, Pace, A, Dorsey, S, Argyriou, A, Kalofonos, H, Briani, C, Schenone, A, Faber, C, Mazzeo, A, Grisold, W, Valsecchi, M, Cavaletti, G, Alberti, Paola, Bernasconi, Davide Paolo, Cornblath, David R., Jose Merkies, Ingemar Sergio, Park, Susanna B, Velasco, Roser, Bruna, Jordi, Psimaras, Dimitri, Susanne, Koeppen, Pace, Andrea, Dorsey, Susan G, Argyriou, Andreas A, Kalofonos, Haralabos P, Briani, Chiara, Schenone, Angelo, Faber, Catharina G, Mazzeo, Anna, Grisold, Wolfgang, Valsecchi, Maria Grazia, Cavaletti, Guido, Alberti, P, Bernasconi, D, Cornblath, D, Jose Merkies, I, Park, S, Velasco, R, Bruna, J, Psimaras, D, Susanne, K, Pace, A, Dorsey, S, Argyriou, A, Kalofonos, H, Briani, C, Schenone, A, Faber, C, Mazzeo, A, Grisold, W, Valsecchi, M, Cavaletti, G, Alberti, Paola, Bernasconi, Davide Paolo, Cornblath, David R., Jose Merkies, Ingemar Sergio, Park, Susanna B, Velasco, Roser, Bruna, Jordi, Psimaras, Dimitri, Susanne, Koeppen, Pace, Andrea, Dorsey, Susan G, Argyriou, Andreas A, Kalofonos, Haralabos P, Briani, Chiara, Schenone, Angelo, Faber, Catharina G, Mazzeo, Anna, Grisold, Wolfgang, Valsecchi, Maria Grazia, and Cavaletti, Guido

Abstract

Background and Objective There is no agreement on the gold standard for detection and grading of chemotherapy-induced peripheral neurotoxicity (CIPN) in clinical trials. The objective is to perform an observational prospective study to assess and compare patient-based and physician-based methods for detection and grading of CIPN. Methods Consecutive patients, aged 18 years or older, candidates for neurotoxic chemotherapy, were enrolled in the United States, European Union, or Australia. A trained investigator performed physician-based scales (Total Neuropathy Score–clinical [TNSc], used to calculate Total Neuropathy Score–nurse [TNSn]) and supervised the patient-completed questionnaire (Functional Assessment of Cancer Treatment/Gynecologic Oncology Group–Neurotoxicity [FACT/GOG-NTX]). Evaluations were performed before and at the end of chemotherapy. On participants without neuropathy at baseline, we assessed the association between TNSc, TNSn, and FACT/GOG-NTX. Considering a previously established minimal clinically important difference (MCID) for FACT/GOG-NTX, we identified participants with and without a clinically important deterioration according to this scale. Then, we calculated the MCID for TNSc and TNSn as the difference in the mean change score of these scales between the 2 groups. Results Data from 254 participants were available: 180 (71%) had normal neurologic status at baseline. At the end of the study, 88% of participants developed any grade of neuropathy. TNSc, TNSn, and FACT/GOG-NTX showed good responsiveness (standardized mean change from baseline to end of chemotherapy >1 for all scales). On the 153 participants without neuropathy at baseline and treated with a known neurotoxic chemotherapy regimen, we verified a moderate correlation in both TNSc and TNSn scores with FACT/GOG-NTX (Spearman correlation index r = 0.6). On the same sample, considering as clinically important a change in the FACT/GOG-NTX score of at least 3.3 points, the MCID was 3.

Published
2021

19. Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin

Author

Alberti, P., Rossi, E., Cornblath, D. R., Merkies, I. S. J., Postma, T. J., Frigeni, B., Bruna, J., Velasco, R., Argyriou, A. A., Kalofonos, H. P., Psimaras, D., Ricard, D., Pace, A., Galiè, E., Briani, C., Dalla Torre, C., Faber, C. G., Lalisang, R. I., Boogerd, W., Brandsma, D., Koeppen, S., Hense, J., Storey, D., Kerrigan, S., Schenone, A., Fabbri, S., Valsecchi, M. G., Cavaletti, G., Cavaletti, G., Cornblath, D.R., Merkies, I.S.J., Postma, T.J., Valsecchi, M.G, Galimberti, S., Rossi, E., Cavaletti, G., Frigeni, B., Lanzani, F., Mattavelli, L., Piatti, ML., Alberti, P., Binda, D., Bidoli, P.., Cazzaniga, M., Cortinovis, D., Bruna, J., Velasco, R., Argyriou, AA., Kalofonos, HP., Psimaras, D., Ricard, D., Pace, A., Galiè, E., Briani, C., Lucchetta, M., Campagnolo, M., Dalla Torre, C., Merkies, ISJ., Faber, CG., Merkies, ISJ., Vanhoutte, EK., Bakkers, M., Brouwer, B., Lalisang, RI., Boogerd, W., Brandsma, D., Koeppen, S., Hense, J., Grant, R., Storey, D., Kerrigan, S., Schenone, A., Reni, L., Piras, B., Fabbri, S., Padua, L., Granata, G., Leandri, M., Ghignotti, I., Plasmati, R.., Pastorelli, F., Postma, TJ., Heimans, JJ., Eurelings, M., Meijer, RJ., Grisold, W., Lindeck Pozza, E., Mazzeo, A., Toscano, A., Tomasello, C., Altavilla, G., Penas Prado, M., Dominguez Gonzalez, C., Dorsey, SG., and Brell, JM.

Published
2014
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20. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: A Hellenic Cooperative Oncology Group study

Author

Fountzilas, G., Dafni, U., Dimopoulos, M. A., Koutras, A., Skarlos, D., Papakostas, P., Gogas, H., Bafaloukos, D., Kalogera-Fountzila, A., Samantas, E., Briasoulis, E., Pectasides, D., Maniadakis, N., Matsiakou, F., Aravantinos, G., Papadimitriou, C., Karina, M., Christodoulou, C., Kosmidis, P., and Kalofonos, H. P.

Published
2009
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22. Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Author

Schmidinger, M. Bamias, A. Procopio, G. Hawkins, R. Sanchez, A.R. Vázquez, S. Srihari, N. Kalofonos, H. Bono, P. Pisal, C.B. Hirschberg, Y. Dezzani, L. Ahmad, Q. Jonasch, E. Gimeno, R.A. Herranz, U.A. Ardavanis, A. Ashraf, S.A. Bamias, A. Barone, C. Bella, S.R. Belz, H. Companario, E.B. Bolling, C. Bono, P. Bothe, K. Carteni, G. Espinosa, J.C. Clausse, M. Confente, C. Coskun, H. Herrero, G.C. Demey, W. D'hondt, R. Santasusana, M.D. Doshi, G. Elkiran, E. Facchini, G. Fein, L. Calvo, O.F. Flaherty, A. Fountzilas, G. Fruehauf, J. Díaz, E.G. Garcia, R. Domínguez, R.G. Ghosn, M. Glorieux, P. Goebell, P.J. Gutierrez, L.G.-A. Gonzalez, M. Green, N.B. Arnau, M.G. Harich, H.-D. Hawkins, R. Hegele, A. Pérez, C.H. Herrmann, E. Horniniger, W.J. Hutson, T.E. Janetschek, G. Kalantari, H. Kalofonos, H. Klausmann, M. Kolin, M. Krause, S. Kroening, H. Sorrosal, J.J.L. Lázaro, M. Lema, M. Lema, M.L. Lin, J. Lueck, A. Lybaert, W. Magi, A. Marina, V.A. Rey, J.P.M. Matus, G. Melear, J. Gonzalez, B.M. Milella, M. Montalar, J. Ferrandis, J.M. Nathan, P. Nechushtan, H. Nusch, A. Ojamaa, K. Oksuzoglu, B. Ozkan, M. Papazisis, K. Passalacqua, R. Pe'er, A. Gracia, J.L.P. Pichler, A. Pokker, H. Porta, C. Rauchenwald, M. Richardet, M.E. Richey, S.L. Garcia, J.M.R. Sánchez, A.R. Rudolph, R. Sabbatini, R. Salmon, J.-P. Lobera, C.S. Sarid, D.L. Saylors, G.B. Schmidinger, M. Schrijvers, D. Schulze, M. Sevilay, A. Shumaker, G.G. Siemer, S. de Prado y Otero, D.S. Srihari, N. Stoiber, F. Rodriguez, C.S. Varela, M.S. Vasanthan, S. Estevez, S.V. Vehling-Kaiser, U. Vogelzang, N. Weiss, H. Whenham, N. Wyendaele, W. Yildiz, R. Yucel, I. Zarba, J.J. Zarkar, A. Zhong, W. Ziem, P. the PRINCIPAL Study Group

Abstract

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months. © AlphaMed Press 2019

Published
2019

24. Pharmacogenetics in model-based optimization of bevacizumab therapy for metastatic colorectal cancer

Author

Papachristos, A. Karatza, E. Kalofonos, H. Sivolapenko, G.

Abstract

Vascular endothelial growth factor A (VEGF-A) and intercellular adhesion molecule 1 (ICAM-1) are significant regulators of angiogenesis, an important biological process involved in carcinogenesis. Bevacizumab, an anti-VEGF monoclonal antibody (MAB), is approved for the treatment of metastatic Colorectal cancer (mCRC), however clinical outcomes are highly variable. In the present study, we developed a pharmacokinetic (PK), a simplified quasi-steady state (QSS) and a pharmacokinetic/pharmacodynamic (PK/PD) model to identify potential sources of variability. A total of 46 mCRC patients, who received bevacizumab in combination with chemotherapy were studied. VEGF-A (rs2010963, rs1570360, rs699947) and ICAM-1 (rs5498, rs1799969) genes’ polymorphisms, age, gender, weight, and dosing scheme were investigated as possible co-variates of the model’s parameters. Polymorphisms, trough, and peak levels of bevacizumab, and free VEGF-A were determined in whole blood and serum. Data were analyzed using nonlinear mixed-effects modeling. The two-compartment PK model showed that clearance (CL) was significantly lower in patients with mutant ICAM-1 rs1799969 (p < 0.0001), inter-compartmental clearance (Q) was significantly higher with mutant VEGF-A rs1570360 (p < 0.0001), and lower in patients with mutant VEGF-A rs699947 (p < 0.0001). The binding QSS model also showed that mutant ICAM-1 rs1799969 was associated with a lower CL (p = 0.0177). Mutant VEGF-A rs699947 was associated with a lower free VEGF-A levels, prior to the next dose (p = 0.000445). The above results were confirmed by the PK/PD model. Findings of the present study indicated that variants of the genes regulating angiogenesis might affect PK and PD characteristics of bevacizumab, possibly influencing the clinical outcomes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2020

25. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Author

Powles, T. van der Heijden, M.S. Castellano, D. Galsky, M.D. Loriot, Y. Petrylak, D.P. Ogawa, O. Park, S.H. Lee, J.-L. De Giorgi, U. Bögemann, M. Bamias, A. Eigl, B.J. Gurney, H. Mukherjee, S.D. Fradet, Y. Skoneczna, I. Tsiatas, M. Novikov, A. Suárez, C. Fay, A.P. Duran, I. Necchi, A. Wildsmith, S. He, P. Angra, N. Gupta, A.K. Levin, W. Bellmunt, J. van der Heijden, M.S. Lee, J.L. Eigl, B.J. Mukherjee, S.D. Suarez, C. Westgeest, H. Flechon, A. Ou, Y.-C. Park, I. Matveev, V. Pérez-Valderrama, B. Cheng, S. Frank, S. Anido, U. Hamzaj, A. Retz, M. Sridhar, S. Scagliotti, G.V. Voortman, J. Alekseev, B. Alyasova, A. Komyakov, B. Dumez, H. Pavic, M. Kimura, G. Mizokami, A. Osanto, S. Arranz, J.A. Piersma, D. Shin, S.J. Karyakin, O. Delgado, I. Gonzalez, J.L. Pang, S.-T. Tran, A. Lipatov, O. Su, W.-P. Flaig, T. Alva, A. Park Kyong, H. Kopyltsov, E. Almagro, E. Domenech, M. Chang, Y.-H. Sautois, B. Ravaux, A. Aravantinos, G. Georgoulias, V. Mulder, S. Kim, Y.J. Kater, F. Chevreau, C. Tagawa, S. Zalewski, P. Joly, F. Hatiboglu, G. Gianni, L. Morelli, F. Tambaro, R. Hashimoto, Y. Nosov, A. Font, A. Rodriguez-Vida, A.M. Jones, R. Vasudev, N. Srinivas, S. Zhang, J. Gil, T. Finch, D. Grimm, M.-O. Su, Y.-L. Chowdhury, S. Hocking, C. Plas, E. North, S. Jensen, N.V. Theodore, C. Imkamp, F. Peer, A. Kobayashi, T. Sakai, H. Sassa, N. Yoshimura, K. Aarts, M. Ferreira Castro, A. Topuzov, M. Rodriguez, J.F. Vazquez, F.J. Tsai, Y.-C. Crabb, S. Hussain, S. Bendell, J. Gross-Goupil, M. Gwenaelle, G. Berger, R. Statsenko, G. Evans, L. Drakaki, A. Somer, B. Davis, I. Lynam, J. Borges, G. Dettino, A. Fay, A.P. Martins, G. Zucca, L.E. Agerbaek, M. Kalofonos, H. Rosenbaum, E. Enokida, H. Kikukawa, H. Nishimura, K. Tamada, S. Uemura, M. Lopez, Y. Gietema, J. Slojewski, M. Fernandes, I. Smolin, A. Mazhar, D. Kalebasty, A.R. Carthon, B. Loidl, W. Franke, F. Girotto, G. Alimohamed, N. Macfarlane, R. Pappot, H. Niegisch, G. Mavroudis, D. Sella, A. Porta, C. Ebara, S. Nakamura, M. Obara, W. Okuno, N. Shinohara, N. Sugimoto, M. Suzuki, A. Tokuda, N. Uemura, H. Yamaguchi, A. Ramirez, F. Rozanowski, P. Wiechno, P. Keam, B. Kislov, N. Plaksin, D. Cicin, I. Kumar, S. Galsky, M.D. Petrylak, D.P. Rosales, J. Vaishampayan, U. Culine, S. Papandreou, C. Nara, T. Erman, M. Kreiger, L. Janoski, J. Rosa, D. Siqueira, M. Canil, C. Sengelov, L. Tourani, J.-M. Arai, G. Hashine, K. Kawakita, M. Nakaigawa, N. Nomi, H. Shiina, H. Suzuki, H. Yonese, J. Kuri, R. Macedo, E. Rivera, S. Villalobos Prieto, A. Polakiewicz-Gilowska, A. Zaucha, R. Lopes, F. Ponomarev, R. Pomerantz, M. Shariat, S. Luk, C. Lesniewski-Kmak, K.

Abstract

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (

Published
2020

26. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Author

Petrylak, D.P. de Wit, R. Chi, K.N. Drakaki, A. Sternberg, C.N. Nishiyama, H. Castellano, D. Hussain, S.A. Fléchon, A. Bamias, A. Yu, E.Y. van der Heijden, M.S. Matsubara, N. Alekseev, B. Necchi, A. Géczi, L. Ou, Y.-C. Coskun, H.S. Su, W.-P. Bedke, J. Gakis, G. Percent, I.J. Lee, J.-L. Tucci, M. Semenov, A. Laestadius, F. Peer, A. Tortora, G. Safina, S. Garcia del Muro, X. Rodriguez-Vida, A. Cicin, I. Harputluoglu, H. Tagawa, S.T. Vaishampayan, U. Aragon-Ching, J.B. Hamid, O. Liepa, A.M. Wijayawardana, S. Russo, F. Walgren, R.A. Zimmermann, A.H. Hozak, R.R. Bell-McGuinn, K.M. Powles, T. Wong, S.-L.S. Tan, T.H. Hovey, E.J. Clay, T.D. Wan Ng, S.S. Rutten, A. Machiels, J.-P. Dumez, H. Cheng, S.Y.-S. Ferrario, C. Sengeloev, L. Jensen, N.V. Thibault, C. Laguerre, B. Joly, F. Culine, S. Becht, C. Niegisch, G. Stöckle, M. Grimm, M.-O. Schwentner, C.A. Schultze-Seemann, W. Kalofonos, H. Mavroudis, D. Papandreou, C. Karavasilis, V. Révész, J. Rosenbaum, E. Leibowitz-Amit, R. Kejzman, D. Sarid, D. Scagliotti, G.V. Bracarda, S. Massari, F. Osawa, T. Miyajima, N. Shinohara, N. Fukuta, F. Ohyama, C. Obara, W. Yamashita, S. Tomita, Y. Kawai, K. Fukasawa, S. Oyama, M. Yonese, J. Nagata, M. Uemura, M. Nishimura, K. Kawakita, M. Tsunemori, H. Hashine, K. Inokuchi, J. Yokomizo, A. Nagamori, S. Lee, H.J. Park, S.H. Rha, S.Y. Kim, Y.J. Lee, Y.-G. Vazquez Cortés, L. Lorena Urzua Flores, C. Blaisse, R.J.B. Erdkamp, F.L.G. Aarts, M.J.B. Wojcik-Tomaszewska, J. Tomczak, P. Sikora-Kupis, B. Schenker, M. Herzal, A.A. Udrea, A.A. Karlov, P. Fomkin, R. Gajate Borau, P. Grande, E. Delgado Mignorance, J.I. Su, Y.-L. Li, J.-R. Lin, C.-L. Lin, C.-C. Yeh, S.-P. Erman, M. Urun, Y. Golovko, Y. Bondarenko, I. Sinielnikov, I. Crabb, S.J. Syndikus, I. Huddart, R. Sundar, S. Chowdhury, S. Sarwar, N. Flaig, T.W. Pan, C.X. Schwarz, J.K. Cultrera, J.L. Acs, P.I. Hainsworth, J.D. Herms, B.T. Lawler, W.E. Lowe, T.E.

Abstract

Background: Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company. © 2020 Elsevier Ltd

Published
2020

31. The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings

Author

Cavaletti, G., Cornblath, D. R., Merkies, I. S. J., Postma, T. J., Rossi, E., Frigeni, B., Alberti, P., Bruna, J., Velasco, R., Argyriou, A. A., Kalofonos, H. P., Psimaras, D., Ricard, D., Pace, A., Galiè, E., Briani, C., Dalla Torre, C., Faber, C. G., Lalisang, R. I., Boogerd, W., Brandsma, D., Koeppen, S., Hense, J., Storey, D., Kerrigan, S., Schenone, A., Fabbri, S., Valsecchi, M. G., Mazzeo, A., Pace, A., Pessino, A., Schenone, A., Toscano, A., Argyriou, A.A., Brouwer, B., Frigeni, B., Piras, B., Briani, C., Dalla Torre, C., Dominguez Gonzalez, C., Faber, C. G., Tomasello, C., Binda, D., Brandsma, D., Cortinovis, D., Psimaras, D., Ricard, D., Storey, D., Cornblath, D.R., Galiè, E., Lindeck Pozza, E., Rossi, E., Vanhoutte, E.K., Lanzani, F., Pastorelli, F., Altavilla, G., Cavaletti, G., Granata, G., Kalofonos, H.P., Ghignotti, I., Merkies, I.S.J., Bruna, J., Hense, J., Heimans, J.J., Mattavelli, L., Padua, L., Reni, L., Bakkers, M., Boogerd, M., Campagnolo, M., Cazzaniga, M., Eurelings, M., Leandri, M., Lucchetta, M., Penas Prado, M., Russo, M., Valsecchi, M.G., Piatti, M.L., Alberti, P., Bidoli, P., Grant, R., Plasmati, R., Velasco, R., Lalisang, R.I., Meijer, R.J., Fabbri, S., Dorsey, S. G., Galimberti, S., Kerrigan, S., Koeppen, S., Postma, T.J., Boogerd, W., and Grisold, W.

Published
2013
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35. 704MO Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100

Author

Grivas, P., primary, Park, S.H., additional, Voog, E., additional, Caserta, C., additional, Perez Valderrama, B., additional, Gurney, H., additional, Kalofonos, H., additional, Radulovic, S., additional, Demey, W., additional, Ullén, A., additional, Loriot, Y., additional, Sridhar, S.S., additional, Tsuchiya, N., additional, Kopyltsov, E., additional, Gupta, S., additional, Huang, B., additional, Costa, N., additional, Blake-Haskins, J.A., additional, di Pietro, A., additional, and Powles, T.B., additional

Published
2020
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37. 1825P Prevention and prophylaxis (thromboprophylaxis - ACT) of cancer associated thrombosis (CAT) in high risk oncology patients: ACT4CAT

Author

Tsoukalas, N.G., primary, Christopoulou, A.N., additional, Papandreou, C., additional, Kapodistrias, N., additional, Koumarianou, A., additional, Peroukidis, S., additional, Kalofonos, H., additional, Samelis, G.F., additional, Andreadis, C., additional, Ardavanis, A., additional, Samantas, E., additional, Bokas, A., additional, Ligdas, A., additional, Athanasiadis, I., additional, Barbounis, V., additional, Kentepozidis, N., additional, Mavroudis, D., additional, Athanasiadis, A., additional, Papakotoulas, P., additional, and Boukovinas, I., additional

Published
2020
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39. Real-world experience of everolimus as second-line treatment in metastatic renal cell cancer after failure of pazopanib

Author

Koutsoukos K, Bamias A, Tzannis K, Espinosa Montaño M, Bozionelou V, Christodoulou C, Stefanou D, Kalofonos H, Duran I, and Papazisis K

Subjects
Pazopanib, Renal Cell Carcinoma, Everolimus, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Konstantinos Koutsoukos,1,2 Aristotelis Bamias,1,2 Kimon Tzannis,1 Marta Espinosa Montaño,3 Vasiliki Bozionelou,4 Christos Christodoulou,5 Dimitra Stefanou,6 Haralabos Kalofonos,7 Ignacio Duran,3 Konstantinos Papazisis1,8 1Hellenic Genito-Urinary Cancer Group, 2Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece; 3Medical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 4Department of Medical Oncology, University Hospital of Heraklion, Heraklion, 52nd Oncology Clinic, Metropolitan Hospital, Piraeus, 61st Department of Medical Oncology, Saint Savvas Anticancer Hospital, Athens, 7Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, 8Euromedica General Clinic, Thessaloniki, Greece Aim: We aimed to provide real-life data on the outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus as second-line treatment after failure of first-line pazopanib.Patients and methods: Data from the medical charts of mRCC patients from 8 centers in Greece and Spain were reviewed. All patients had received or were continuing to receive second-line everolimus treatment after failure of first-line treatment with pazopanib. No other previous therapies were allowed. The primary end point was the determination of progression-free survival (PFS).Results: In total, 31 patients were enrolled. Of these, 26% had performance status (PS) >0, 88% were of intermediate/poor Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, and only 61% had undergone prior nephrectomy. Median PFS was 3.48months (95%CI: 2.37–5.06months). Median overall survival (OS) from everolimus initiation was 8.9months (95%CI: 6.47–13.14 months). Median OS from pazopanib initiation was 14.78months (95%CI: 10.54–19.08months). Furthermore, 32% of patients temporarily discontinued everolimus due to adverse events (AEs), and 22% of patients discontinued everolimus permanently due to toxicity. Most common toxicities were anemia (29%), stomatitis (26%), pneumonitis (19%), and fatigue (10%). Moreover, 14 AEs (27%) were graded as 3 or 4 and were reported by 13patients (42%).Conclusion: This study provides data exclusively on the sequence pazopanib–everolimus in mRCC. Everolimus has a favorable safety profile and is active. The short PFS and OS could be attributed to the fact that the pazopanib–everolimus sequence was mainly offered to patients with adverse prognostic features, resulting in a modest increase in the combined OS of our population. Keywords: pazopanib, everolimus, renal cell carcinoma

Published
2017

44. Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00

Author

Fountzilas, G., Dafni, U., Gogas, H., Linardou, H., Kalofonos, H. P., Briasoulis, E., Pectasides, D., Samantas, E., Bafaloukos, D., Stathopoulos, G. P., Karina, M., Papadimitriou, C., Skarlos, D., Pisanidis, N., Papakostas, P., Markopoulos, C., Tzorakoeleftherakis, E., Dimitrakakis, K., Makrantonakis, P., Xiros, N., Polichronis, A., Varthalitis, I., Karanikiotis, C., and Dimopoulos, A. M.

Published
2008

46. Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Author

Vergote, I. Scambia, G. O'Malley, D.M. Van Calster, B. Park, S.-Y. del Campo, J.M. Meier, W. Bamias, A. Colombo, N. Wenham, R.M. Covens, A. Marth, C. Raza Mirza, M. Kroep, J.R. Ma, H. Pickett, C.A. Monk, B.J. Park, S.Y. Song, Y.S. Makarova, Y. Trinidad, J. Ngan, H.Y.S. Aravantinos, G. Nam, J.-H. Gorbunova, V. Krikunova, L. Bae, D.-S. Arija, J.A.A. Mirza, M.R. Zamagni, C. Papandreou, C. Raspagliesi, F. Lisyanskaya, A. Benzaquen, A.O. Tognon, G. Ortega, E. Herraez, A.C. Buscema, J. Green, A. Burger, R. Sakaeva, D. Sanchez, A.R. Ghamande, S. King, L. Petru, E. Peen, U. Takeuchi, S. Ushijima, K. Martin, A.G. Kamelle, S. Carney, M. Forget, F. Bentley, J. Sehouli, J. Zola, P. Kato, H. Fadeeva, N. Gotovkin, E. Vladimirov, V. Marin, M.R. Alia, E.G. Shahin, M. Bhoola, S. Tewari, K. Anderson, D. Honhon, B. Pelgrims, J.G. Oza, A. Jimenez, J.G.-D. Hansen, V. Benjamin, I. Renard, V. Van den Bulck, H. Haenle, C. Koumakis, G. Yokota, H. Popov, V. Bradley, W. Wenham, R. Reid, R. McNamara, D. Friedman, R. Barlin, J. Spirtos, N. Chapman, J. Sevelda, P. Huizing, M. Lamot, C. Goffin, F. Hondt, L.D. Covens, A. Spadafora, S. Rautenberg, B. Reimer, T. Möbus, V. Hilpert, F. Gropp-Meier, M. Savarese, A. Pignata, S. Verderame, F. Mizuno, M. Takano, H. Ottevanger, P. Velasco, A.P. Palacio-Vazquez, I. Law, A. McIntyre, K. Teneriello, M. Fields, A. Lentz, S. Street, D. Schwartz, B. Mannel, R. Lim, P. Pulaski, H. Janni, W. Zorr, A. Karck, U. Cheng, A.C.K. Sorio, R. Gridelli, C. Aoki, D. Oishi, T. Hirashima, Y. Boere, I. Ferrer, E.F. Braly, P. Wilks, S. Lee, C. Schilder, J. Veljovich, D. Secord, A. Davis, K. Rojas-Espaillat, L. Lele, S. DePasquale, S. Squatrito, R. Schauer, C. Dirix, L. Vuylsteke, P. Joosens, E. Provencher, D. Lueck, H.-J. Hein, A. Burges, A. Canzler, U. Park-Simon, T.-W. Griesinger, F. Gadducci, A. Alabiso, O. Okamoto, A. Sawasaki, T. Saito, T. Ibañez, A.H. Calomeni, C. Spillman, M. Choksi, J. Taylor, N. Muller, C. Moore, D. DiSilvestro, P. Cunningham, M. Rose, P. Oppelt, P. Verhoeven, D. Graas, M.-P. Ghatage, P. Tonkin, K. Kurzeder, C. Schnappauf, B. Müller, V. Schmalzrie, H. Kalofonos, H. Bruzzone, M. Kroep, J. Diaz, C.C. Garcia, J.M. Polo, S.H. Garrison, M. Rocconi, R. Andrews, S. Bristow, R. McHale, M. Basil, J. Houck III, W. Bell, M. Cosin, J. Modesitt, S. Kendrick, J. Wade III, J. Wong, C. Evans, A. Buekers, T. Vanderkwaak, T. Ferriss, J. Darus, C. DAndre, S. Higgins, R. Monk, B. Bakkum-Gamez, J. DeMars, L. Van Le, L. Puls, L. Trehan, S. LaPolla, J. Michelson, E.D. Merchant, J. Peterson, C. Reid, G. Seago, D. Zweizig, S. Gajewski, W. Panwalkar, A. Leikermoser, R. Bogner, G. Debruyne, P. D'hondt, R. Berteloot, P. Kerger, J. Biagi, J. Castonguay, V. Welch, S. Muhic, A. Heubner, M. Grischke, E.-M. Rack, B. Fleisch, M. Lordick, F. Pectasides, D. Ho, W.M. Selvaggi, L. Vasquez, F.M. Villanueva, W.O.B. Alavez, A.M. Kessels, L. Bertran, A.S. Fernandez, C.M. Fabregat, M.B. Del Prete, S. Elkas, J. Cecchi, G. Kumar, P. Huh, W. Messing, M. Karimi, M. Kelley, A. Edraki, B. Mutch, D. Leiserowitz, G. Anderson, J. Lentz, S. Chambers, S. Morris, R. Waggoner, S. Gordon, A. Method, M. Johnson, P. Lord, R. Drake, J. Sivarajan, K. Midathada, M. Rice, K. Wadsworth, T. Pavelka, J. Edwards, R. Miller, D.S. Ford, P.L. Hurteau, J. Bender, D. Schimp, V. Creasman, W. Lerner, R. Chamberlain, D. Kueck, A. McDonald, J. Malad, S. Robinson-Bennett, B. Davidson, S. Krivak, T. Lestingi, T. Arango, H. Berard, P. Finkelstein, K. Gaur, R. Krasner, C. Ueland, F. Talmage, L. Yamada, S. Sutton, G. Potkul, R. Prasad-Hayes, M. Osborne, J. Celano, P. Thigpen, J. Sharma, S. Schilder, R. Tammela, J. Kemeny, M. Brown, A. Eisenhauer, E. Williams, J. Rowland, K. Nahum, K. Burke, J. Dar, Z. Fleming, N. Gibb, R. Guirguis, A. Herzog, T. John, V. Kumar, S. Kamat, A. Kassar, M. Leitao, M. Levine, L. Mendez, L. Patel, D. Berry, E. Warshal, D. Wolf, J. Zarwan, C. Collins, Y. Spitzer, G. Miller, B. Einstein, M. TRINOVA-3/ENGOT-ov2/GOG-3001 investigators

Abstract

Background: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. Methods: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres)in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO)stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1)using a permuted block method (block size of six patients)to receive six cycles of paclitaxel (175 mg/m2)and carboplatin (area under the serum concentration-time curve 5 or 6)every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. Findings: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7–34·2), 626 patients had progression-free survival events (405 [60%]of 678 in the trebananib group and 221 [66%]of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0–17·6])and the placebo group (15·0 months [12·6–16·1])groups (hazard ratio 0·93 [95% CI 0·79–1·09]; p=0·36). 512 (76%)of 675 patients in the trebananib group and 237 (71%)of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%]vs placebo 126 [38%])anaemia (76 [11%]vs 40 [12%]), and leucopenia (81 [12%]vs 35 [10%]). 269 (40%)patients in the trebananib group and 104 (31%)in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. Interpretation: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. Funding: Amgen. © 2019 Elsevier Ltd

Published
2019

47. Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Author

Procopio, G. Bamias, A. Schmidinger, M. Hawkins, R. Sánchez, A.R. Estevez, S.V. Srihari, N. Kalofonos, H. Bono, P. Pisal, C.B. Hirschberg, Y. Dezzani, L. Ahmad, Q. Rodriguez, C.S. Jonasch, E.

Abstract

Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. Results: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. Conclusions: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes. © 2019 Patients with intermediate-risk advanced renal cell carcinoma are a heterogeneous population, having either 1 or 2 risk factors. It is unclear whether all patients in this risk category should be treated similarly. A secondary analysis of the PRINCIPAL study of pazopanib found that patients can be stratified by number of risk factors and Eastern Cooperative Oncology Group performance status to more accurately predict outcomes. © 2019

Published
2019

50. Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced non–nasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group

Author

Fountzilas, G., Papakostas, P., Dafni, U., Makatsoris, T., Karina, M., Kalogera-Fountzila, A., Maniadakis, N., Aravantinos, G., Syrigos, K., Bamias, A., Christodoulou, C., Economopoulos, T., Kalofonos, H. P., Nikolaou, A., Angouridakis, N., Stathopoulos, G., Bafaloukos, D., Pavlidis, N., and Daniilidis, J.

Published
2006

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