13 results on '"Zimmermann AH"'
Search Results
2. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial
- Author
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Petrylak, Dp, de Wit, R, Chi, Kn, Drakaki, A, Sternberg, Cn, Nishiyama, H, Castellano, D, Hussain, S, Flechon, A, Bamias, A, Yu, Ey, van der Heijden, M, Matsubara, N, Alekseev, B, Necchi, A, Geczi, L, Ou, Yc, Coskun, H, Su, Wp, Hegemann, M, Percent, Ij, Lee, Jl, Tucci, M, Semenov, A, Laestadius, F, Peer, A, Tortora, Giampaolo, Safina, S, del Muro, Xg, Rodriguez-Vida, A, Cicin, I, Harputluoglu, H, Widau, Rc, Liepa, Am, Walgren, Ra, Hamid, O, Zimmermann, Ah, Bell-McGuinn, Km, Powles, T, Tortora, G (ORCID:0000-0002-1378-4962), Petrylak, Dp, de Wit, R, Chi, Kn, Drakaki, A, Sternberg, Cn, Nishiyama, H, Castellano, D, Hussain, S, Flechon, A, Bamias, A, Yu, Ey, van der Heijden, M, Matsubara, N, Alekseev, B, Necchi, A, Geczi, L, Ou, Yc, Coskun, H, Su, Wp, Hegemann, M, Percent, Ij, Lee, Jl, Tucci, M, Semenov, A, Laestadius, F, Peer, A, Tortora, Giampaolo, Safina, S, del Muro, Xg, Rodriguez-Vida, A, Cicin, I, Harputluoglu, H, Widau, Rc, Liepa, Am, Walgren, Ra, Hamid, O, Zimmermann, Ah, Bell-McGuinn, Km, Powles, T, and Tortora, G (ORCID:0000-0002-1378-4962)
- Abstract
Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population.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 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m(2) plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125.Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4.07 months [95% CI 2.96-4.47] vs 2.76 months [2.60-2.96]; hazard ratio [HR] 0.757, 95% CI 0.607-0.943; p=0.0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24.5%, 95% CI 18.8-30.3) of 216 patients allocated ramucirumab and 31 (14.0%, 9.4-18.6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at g
- Published
- 2017
3. Centrality, rapidity and transverse momentum dependence of J/ψ suppression in Pb–Pb collisions at √sNN = 2.76 TeV
- Author
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Piano, Stefano, Lea, Ramona, Camerini, Paolo, Luparello, Grazia, Fragiacomo, Enrico, Margagliotti, Giacomo, Rui, Rinaldo, Abelev bv, B., Adam al, J., Adamová cd, D., Aggarwal ch, M. M., Aglieri Rinella ah, G., Agnello cn, M., Agocs eb, A. G., Agostinelli z, A., Agrawal as, N., Ahammed dx, Z., Ahmad r, N., Ahmad Masoodi r, A., Ahmed o, I., Ahn bo, S. U., Ahn bo, S. A., Aimo de, I., Aiola ec, S., Ajaz o, M., Akindinov be, A., Aleksandrov ct, D., Alessandro de, B., Alexandre cv, D., Alici l, A., Alkin c, A., Alme aj, J., Alt an, T., Altini ae, V., Altinpinar q, S., Altsybeev dw, I., Alves Garcia Prado dm, C., Andrei by, C., Andronic cq, A., Anguelov cm, V., Anielski az, J., Anticˇic ́ cr, T., Antinori db, F., Antonioli cy, P., Aphecetche df, L., Appelshäuser ax, H., Arbor br, N., Arcelli z, S., Armesto p, N., Arnaldi de, R., Aronsson ec, T., Arsene u, I. C., Arslandok ax, M., Augustinus ah, A., Averbeck cq, R., Awes ce, T. C., Azmi r, M. D., Bach an, M., Badalà da, A., Baek ao, Y. W., Bagnasco de, S., Bailhache ax, R., Bairathi cl, V., Bala ck, R., Baldisseri n, A., Baltasar Dos Santos Pedrosa ah, F., Bán bf, J., Baral bh, R. C., Barbera aa, R., Barile ae, F., Barnaföldi eb, G. G., Barnby cv, L. S., Barret bq, V., Bartke dj, J., Basile z, M., Bastid bq, N., Basu dx, S., Bathen az, B., Batigne df, G., Batyunya bm, B., Batzing u, P. C., Baumann ax, C., Bearden ca, I. G., Beck ax, H., Bedda cn, C., Behera as, N. K., Belikov ba, I., Bellini z, F., Bellwied do, R., Belmont Moreno bk, E., Bencedi eb, G., Beole y, S., Berceanu by, I., Bercuci by, A., Berdnikov cf, Y., 1, Berenyi eb, D., Berger di, M. E., Bergognon df, A. A. E., Bertens bd, R. A., Berzano y, D., Betev ah, L., Bhasin ck, A., Bhati ch, A. K., Bhattacharjee ap, B., Bhom dt, J., Bianchi y, L., Bianchi bs, N., Bianchin bd, C., Bielcˇík al, J., Bielcˇíková cd, J., Bilandzic ca, A., Bjelogrlic bd, S., Blanco j, F., Blau ct, D., Blume ax, C., Bock bu, F., Boehmer di, F. V., Bogdanov bw, A., Bøggild ca, H., Bogolyubsky bb, M., Boldizsár eb, L., Bombara am, M., Book ax, J., Borel n, H., Borissov cp, A., Bornschein an, J., Bossú bl, F., Botje cb, M., Botta y, E., Böttger aw, S., Braun Munzinger cq, P., Bregant dm, M., Breitner aw, T., Broker ax, T. A., Browning co, T. A., Broz ak, M., Bruna de, E., Bruno ae, G. E., Budnikov cs, D., Buesching ax, H., Bufalino de, S., Buncic ah, P., Busch cm, O., Buthelezi bl, Z., Caffarri ab, D., Cai g, X., Caines ec, H., Caliva bd, A., Calvo Villar cw, E., Canoa Roman ah, V., Carena ah, F., Carena ah, W., Carminati ah, F., Casanova Díaz bs, A., Castillo Castellanos n, J., Casula w, E. A. R., Catanescu by, V., Cavicchioli ah, C., Ceballos Sanchez i, C., Cepila al, J., Cerello de, P., Chang dp, B., Chapeland ah, S., Charvet n, J. L., Chattopadhyay dx, S., Chattopadhyay cu, S., Cherney cg, M., Cheshkov dv, C., Cheynis dv, B., Chibante Barroso ah, V., Chinellato do, D. D., Chochula ah, P., Chojnacki ca, M., Choudhury dx, S., Christakoglou cb, P., Christensen ca, C. H., Christiansen af, P., Chujo dt, T., Chung cp, S. U., Cicalo cz, C., Cifarelli l, L., Z, Cindolo cy, F., Cleymans cj, J., Colamaria ae, F., Colella ae, D., Collu w, A., Colocci z, M., Conesa Balbastre br, G., Conesa del Valle av, Z., Connors ec, M. E., Contin x, G., Contreras k, J. G., Cormier ce, T. M., Corrales Morales y, Y., Cortese ad, P., Cortés Maldonado b, I., Cosentino bu, M. R., Costa ah, F., Crochet bq, P., Cruz Albino k, R., Cuautle bj, E., Cunqueiro bs, L., Dainese db, A., Dang g, R., Danu bi, A., Das cu, D., Das av, I., Das cu, K., Das d, S., Dash dn, A., Dash as, S., De dx, S., Delagrange df, H., 2, Deloff bx, A., Dénes eb, E., D’Erasmo ae, G., de Barros dm, G. O. V., De Caro l, A., de Cataldo cx, G., de Cuveland an, J., De Falco w, A., De Gruttola ac, D., L, De Marco de, N., De Pasquale ac, S., de Rooij bd, R., Diaz Corchero j, M. A., Dietel az, T., Divià ah, R., Di Bari ae, D., Di Liberto dc, S., Di Mauro ah, A., Di Nezza bs, P., Djuvsland q, Ø., Dobrin bd, A., Dobrowolski bx, T., Domenicis Gimenez dm, D., Dönigus ax, B., Dordic u, O., Dorheim di, S., Dubey dx, A. K., Dubla bd, A., Ducroux dv, L., Dupieux bq, P., Dutta Majumdar cu, A. K., Elia cx, D., Engel aw, H., Erazmus ah, B., Erdal aj, H. A., Eschweiler an, D., Espagnon av, B., Estienne df, M., Esumi dt, S., Evans cv, D., Evdokimov bb, S., Eyyubova u, G., Fabris db, D., Faivre br, J., Falchieri z, D., Fantoni bs, A., Fasel cm, M., Fehlker q, D., Feldkamp az, L., Felea bi, D., Feliciello de, A., Feofilov dw, G., Ferencei cd, J., Fernández Téllez b, A., Ferreiro p, E. G., Ferretti y, A., Festanti ab, A., Figiel dj, J., Figueredo dm, M. A. S., Filchagin cs, S., Finogeev bc, D., Fionda ae, F. M., Fiore ae, E. M., Floratos ci, E., Floris ah, M., Foertsch bl, S., Foka cq, P., Fokin ct, S., Francescon ab, A., Frankenfeld cq, U., Fuchs ah, U., Furget br, C., Fusco Girard ac, M., Gaardhøje ca, J. J., Gagliardi y, M., Gallio y, M., Gangadharan s, D. R., Ganoti ce, P., Garabatos cq, C., Garcia Solis m, E., Gargiulo ah, C., Garishvili bv, I., Gerhard an, J., Germain df, M., Gheata ah, A., Gheata ah, M., Ghidini ae, B., Ghosh dx, P., Ghosh d, S. K., Gianotti bs, P., Giubellino ah, P., Gladysz Dziadus dj, E., Glässel cm, P., Gomez k, R., González Zamora j, P., Gorbunov an, S., Görlich dj, L., Gotovac dh, S., Graczykowski dz, L. K., Grajcarek cm, R., Grelli bd, A., Grigoras ah, A., Grigoras ah, C., Grigoriev bw, V., Grigoryan a, A., Grigoryan bm, S., Grinyov c, B., Grion dd, N., Grosse Oetringhaus ah, J. F., Grossiord dv, J. Y., Grosso ah, R., Guber bc, F., Guernane br, R., Guerzoni z, B., Guilbaud dv, M., Gulbrandsen ca, K., Gulkanyan a, H., Gunji ds, T., Gupta ck, A., Gupta ck, R., Khan o, K. H., Haake az, R., Haaland q, Ø., Hadjidakis av, C., Haiduc bi, M., Hamagaki ds, H., Hamar eb, G., Hanratty cv, L. D., Hansen ca, A., Harris ec, J. W., Hartmann an, H., Harton m, A., Hatzifotiadou cy, D., Hayashi ds, S., Hayrapetyan ah, A., A, Heckel ax, S. T., Heide az, M., Helstrup aj, H., Herghelegiu by, A., Herrera Corral k, G., Hess ag, B. A., Hetland aj, K. F., Hicks ec, B., Hippolyte ba, B., Hladky bg, J., Hristov ah, P., Huang q, M., Humanic s, T. J., Hutter an, D., Hwang t, D. S., Ianigro dv, J. C., Ilkaev cs, R., Ilkiv bx, I., Inaba dt, M., Incani w, E., Innocenti y, G. M., Ionita ah, C., Ippolitov ct, M., Irfan r, M., Ivanov cq, M., Ivanov cf, V., Ivanytskyi c, O., Jachołkowski aa, A., Jahnke dm, C., Jang bo, H. J., Janik dz, M. A., Jayarathna do, P. H. S. Y., Jena as, S., Jimenez Bustamante bj, R. T., Jones cv, P. G., Jung ao, H., Jusko cv, A., Kalcher an, S., Kalinak bf, P., Kalweit ah, A., Kamin ax, J., Kang ed, J. H., Kaplin bw, V., Kar dx, S., Karasu Uysal bp, A., Karavichev bc, O., Karavicheva bc, T., Karpechev bc, E., Kebschull aw, U., Keidel ee, R., Ketzer ai, B., Khan r, M. M., 3, Khan cu, P., Khan dx, S. A., Khanzadeev cf, A., Kharlov bb, Y., Kileng aj, B., Kim ed, B., Kim bo, D. W., Kim dp, D. J., Kim ao, J. S., Kim ao, M., Kim ed, M., Kim t, S., Kim ed, T., Kirsch an, S., Kisel an, I., Kiselev be, S., Kisiel dz, A., Kiss eb, G., Klay f, J. L., Klein cm, J., Klein Bösing az, C., Kluge ah, A., Knichel cq, M. L., Knospe dk, A. G., Kobdaj dg, C., Köhler cq, M. K., Kollegger an, T., Kolojvari dw, A., Kondratiev dw, V., Kondratyeva bw, N., Konevskikh bc, A., Kovalenko dw, V., Kowalski dj, M., Kox br, S., Koyithatta Meethaleveedu as, G., Kral dp, J., Králik bf, I., Kramer ax, F., Kravcˇáková am, A., Krelina al, M., Kretz an, M., Krivda cv, M., Krizek cd, F., Krus al, M., Kryshen cf, E., Krzewicki cq, M., Kucˇera cd, V., Kucheriaev ct, Y., Kugathasan ah, T., Kuhn ba, C., Kuijer cb, P. G., Kulakov ax, I., Kumar as, J., Kurashvili bx, P., Kurepin bc, A., Kurepin bc, A. B., Kuryakin cs, A., Kushpil cd, S., Kushpil cd, V., Kweon cm, M. J., Kwon ed, Y., Ladron de Guevara bj, P., Lagana Fernandes dm, C., Lakomov av, I., Langoy dy, R., Lara aw, C., Lardeux df, A., Lattuca y, A., La Pointe bd, S. L., La Rocca aa, P., Lee cv, G. R., Legrand ah, I., Lehnert ax, J., Lemmon cc, R. C., Lenhardt cq, M., Lenti cx, V., Leogrande bd, E., Leoncino y, M., León Monzón dl, I., Lévai eb, P., Li bq, S., G, Lien dy, J., Q, Lietava cv, R., Lindal u, S., Lindenstruth an, V., Lippmann cq, C., Lisa s, M. A., Ljunggren af, H. M., Lodato bd, D. F., Loenne q, P. I., Loggins ea, V. R., Loginov bw, V., Lohner cm, D., Loizides bu, C., Lopez bq, X., López Torres i, E., Lu cm, X. G., Luettig ax, P., Lunardon ab, M., Luo g, J., Luzzi ah, C., Gago cw, A. M., Jacobs bu, P. M., Ma ec, R., Maevskaya bc, A., Mager ah, M., Mahapatra bh, D. P., Maire cm, A., Malaev cf, M., Maldonado Cervantes bj, I., Malinina bm, L., 4, Mal’Kevich be, D., Malzacher cq, P., Mamonov cs, A., Manceau de, L., Manko ct, V., Manso bq, F., Manzari cx, V., Marchisone bq, M., Y, Mareš bg, J., Margotti cy, A., Marín cq, A., Markert ah, C., Marquard ax, M., Martashvili dr, I., Martin cq, N. A., Martinengo ah, P., Martínez b, M. I., Martínez García df, G., Martin Blanco df, J., Martynov c, Y., Mas df, A., Masciocchi cq, S., Masera y, M., Masoni cz, A., Massacrier df, L., Mastroserio ae, A., Matyja dj, A., Mayer dj, C., Mazer dr, J., Mazumder at, R., Mazzoni dc, M. A., Meddi v, F., Menchaca Rocha bk, A., Mercado Pérez cm, J., Meres ak, M., Miake dt, Y., Mikhaylov be, K., Milano ah, L., Milosevic u, J., 5, Mischke bd, A., Mishra at, A. N., Mis ́kowiec cq, D., Mitu bi, C. M., Mlynarz ea, J., Mohanty dx, B., Molnar ba, L., Montaño Zetina k, L., Montes j, E., Morando ab, M., Moreira De Godoy dm, D. A., Moretto ab, S., Morreale dp, A., Morsch ah, A., Muccifora bs, V., Mudnic dh, E., Muhuri dx, S., Mukherjee dx, M., Müller ah, H., Munhoz dm, M. G., Murray cj, S., Musa ah, L., Musinsky bf, J., Nandi as, B. K., Nania cy, R., Nappi cx, E., Nattrass dr, C., Nayak dx, T. K., Nazarenko cs, S., Nedosekin be, A., Nicassio cq, M., Niculescu ah, M., Nielsen ca, B. S., Nikolaev ct, S., Nikulin ct, S., Nikulin cf, V., Nilsen cg, B. S., Noferini l, F., Nomokonov bm, P., Nooren bd, G., Nyanin ct, A., Nyatha as, A., Nystrand q, J., Oeschler cm, H., Oh ec, S., Oh bn, S. K., Ao, 6, Okatan bp, A., Olah eb, L., Oleniacz dz, J., Oliveira Da Silva dm, A. C., Onderwaater cq, J., Oppedisano de, C., Ortiz Velasquez af, A., Oskarsson af, A., Otwinowski cq, J., Oyama cm, K., Pachmayer cm, Y., Pachr al, M., Pagano ac, P., Paic ́ bj, G., Painke an, F., Pajares p, C., Pal dx, S. K., Palmeri da, A., Pant as, D., Papikyan a, V., Pappalardo da, G. S., Park cq, W. J., Passfeld az, A., Patalakha bb, D. I., Paticchio cx, V., Paul cu, B., Pawlak dz, T., Peitzmann bd, T., Pereira Da Costa n, H., Pereira De Oliveira Filho dm, E., Peresunko ct, D., Pérez Lara cb, C. E., Peryt dz, W., Pesci cy, A., Pestov e, Y., Petrácˇek al, V., Petran al, M., Petris by, M., Petrovici by, M., Petta aa, C., Pikna ak, M., Pillot df, P., Pinazza ah, O., Pinsky do, L., Piyarathna do, D. B., Planinic cr, M., Płoskon ́ bu, M., Pluta dz, J., Pochybova eb, S., Podesta Lerma dl, P. L. M., Poghosyan ah, M. G., Pohjoisaho aq, E. H. O., Polichtchouk bb, B., Poljak cr, N., Pop by, A., Porteboeuf Houssais bq, S., Porter bu, J., Pospisil al, V., Potukuchi ck, B., Prasad ea, S. K., D, Preghenella cy, R., Prino de, F., Pruneau ea, C. A., Pshenichnov bc, I., Puddu w, G., Pujahari ea, P., Punin cs, V., Putschke ea, J., Qvigstad u, H., Rachevski dd, A., Raha d, S., Rak dp, J., Rakotozafindrabe n, A., Ramello ad, L., Raniwala cl, R., Raniwala cl, S., Räsänen aq, S. S., Rascanu ax, B. T., Rathee ch, D., Rauf o, A. W., Razazi w, V., Read dr, K. F., Real br, J. S., Redlich bx, K., 7, Reed ec, R. J., Rehman q, A., Reichelt ax, P., Reicher bd, M., Reidt ah, F., Renfordt ax, R., Reolon bs, A. R., Reshetin bc, A., Rettig an, F., Revol ah, J. P., Reygers cm, K., Riabov cf, V., Ricci bt, R. A., Richert af, T., Richter u, M., Riedler ah, P., Riegler ah, W., Riggi aa, F., Rivetti de, A., Rocco bd, E., Rodríguez Cahuantzi b, M., Rodriguez Manso cb, A., Røed u, K., Rogochaya bm, E., Rohni ck, S., Rohr an, D., Röhrich q, D., Romita dq, R., Ronchetti bs, F., Ronflette df, L., Rosnet bq, P., Rossegger ah, S., Rossi ah, A., Roy at, A., Roy ba, C., Roy cu, P., Rubio Montero j, A. J., Russo y, R., Ryabinkin ct, E., Ryabov cf, Y., Rybicki dj, A., Sadovsky bb, S., Šafarˇík ah, K., Sahlmuller ax, B., Sahoo at, R., Sahu bh, P. K., Saini dx, J., Salgado p, C. A., Salzwedel s, J., Sambyal ck, S., Samsonov cf, V., Sanchez Castro ba, X., Sánchez Rodríguez dl, F. J., Šándor bf, L., Sandoval bk, A., Sano dt, M., Santagati aa, G., Sarkar dx, D., Scapparone cy, E., Scarlassara ab, F., Scharenberg co, R. P., Schiaua by, C., Schicker cm, R., Schmidt cq, C., Schmidt ag, H. R., Schuchmann ax, S., Schukraft ah, J., Schulc al, M., Schuster ec, T., Schutz ah, Y., Schwarz cq, K., Schweda cq, K., Scioli z, G., Scomparin de, E., Scott cv, P. A., Scott dr, R., Segato ab, G., Seger cg, J. E., Selyuzhenkov cq, I., Seo cp, J., Serradilla j, E., Sevcenco bi, A., Shabetai df, A., Shabratova bm, G., Shahoyan ah, R., Shangaraev bb, A., Sharma dr, N., Sharma ck, S., Shigaki ar, K., Shtejer y, K., Sibiriak ct, Y., Siddhanta cz, S., Siemiarczuk bx, T., Silvermyr ce, D., Silvestre br, C., Simatovic du, G., Singaraju dx, R., Singh ck, R., Singha bz, S., Singhal dx, V., Sinha dx, B. C., Sinha cu, T., Sitar ak, B., Sitta ad, M., Skaali u, T. B., Skjerdal q, K., Smakal al, R., Smirnov ec, N., Snellings bd, R. J. M., Søgaard af, C., Soltz bv, R., Song cp, J., Song ed, M., Soramel ab, F., Sorensen dr, S., Spacek al, M., Sputowska dj, I., Spyropoulou Stassinaki ci, M., Srivastava co, B. K., Stachel cm, J., Stan bi, I., Stefanek bx, G., Steinpreis s, M., Stenlund af, E., Steyn bl, G., Stiller cm, J. H., Stocco df, D., Stolpovskiy bb, M., Strmen ak, P., Suaide dm, A. A. P., Subieta Vasquez y, M. A., Sugitate ar, T., Suire av, C., Suleymanov o, M., Sultanov be, R., Šumbera cd, M., Susa cr, T., Symons bu, T. J. M., Szanto de Toledo dm, A., Szarka ak, I., Szczepankiewicz ah, A., Szymanski dz, M., Takahashi dn, J., Tangaro ae, M. A., Tapia Takaki av, J. D., 8, Tarantola Peloni ax, A., Tarazona Martinez ah, A., Tauro ah, A., Tejeda Muñoz b, G., Telesca ah, A., Terrevoli ae, C., Ter Minasyan ct, A., Thäder cq, J., Thomas bd, D., Tieulent dv, R., Timmins do, A. R., Toia db, A., Torii ds, H., Trubnikov c, V., Trzaska dp, W. H., Tsuji ds, T., Tumkin cs, A., Turrisi db, R., Tveter u, T. S., Ulery ax, J., Ullaland q, K., Ulrich aw, J., Uras dv, A., Usai w, G. L., Vajzer cd, M., Vala bf, M., Valencia Palomo bq, L., Vallero y, S., Vande Vyvre ah, P., Vannucci bt, L., Van Hoorne ah, J. W., van Leeuwen bd, M., Vargas b, A., Varma as, R., Vasileiou ci, M., Vasiliev ct, A., Vechernin dw, V., Veldhoen bd, M., Venaruzzo x, M., Vercellin y, E., Vergara Limón b, S., Vernet h, R., Verweij ea, M., Vickovic dh, L., Viesti ab, G., Viinikainen dp, J., Vilakazi bl, Z., Villalobos Baillie cv, O., Vinogradov ct, A., Vinogradov dw, L., Vinogradov cs, Y., Virgili ac, T., Viyogi dx, Y. P., Vodopyanov bm, A., Völkl cm, M. A., Voloshin be, K., Voloshin ea, S. A., Volpe ah, G., von Haller ah, B., Vorobyev dw, I., Vranic cq, D., Vrláková am, J., Vulpescu bq, B., Vyushin cs, A., Wagner q, B., Wagner cq, J., Wagner al, V., Wang g, M., Wang cm, Y., Watanabe dt, D., Weber do, M., Wessels az, J. P., Westerhoff az, U., Wiechula ag, J., Wikne u, J., Wilde az, M., Wilk bx, G., Wilkinson cm, J., Williams cy, M. C. S., Windelband cm, B., Winn cm, M., Xiang g, C., Yaldo ea, C. G., Yamaguchi ds, Y., Yang n, H., Yang g, P., Yang q, S., Yano ar, S., Yasnopolskiy ct, S., Yi cp, J., Yin g, Z., Yoo cp, I. K., Yushmanov ct, I., Zaccolo ca, V., Zach al, C., Zaman o, A., Zampolli cy, C., Zaporozhets bm, S., Zarochentsev dw, A., Závada bg, P., Zaviyalov cs, N., Zbroszczyk dz, H., Zgura bi, I. S., Zhalov cf, M., Zhang g, F., Zhang g, H., Zhang bq, X., Bu, G, Zhang g, Y., Zhao u, C., Zhou g, D., Zhou g, F., Zhou bd, Y., Zhu g, H., Zhu g, J., Zhu g, X., Zichichi l, A., Zimmermann cm, A., Zimmermann ah, M. B., Zinovjev c, G., Zoccarato dv, Y., Zynovyev c, M., Zyzak, M., Contin, Giacomo, Piano, Stefano, Lea, Ramona, Camerini, Paolo, Luparello, Grazia, Fragiacomo, Enrico, Margagliotti, Giacomo, Rui, Rinaldo, B., Abelev bv, J., Adam al, D., Adamová cd, M. M., Aggarwal ch, G., Aglieri Rinella ah, M., Agnello cn, De, A. G., Agocs eb, A., Agostinelli z, N., Agrawal a, Z., Ahammed dx, N., Ahmad r, A., Ahmad Masoodi r, I., Ahmed o, S. U., Ahn bo, S. A., Ahn bo, I., Aimo de, Cn, S., Aiola ec, M., Ajaz o, A., Akindinov be, D., Aleksandrov ct, B., Alessandro de, D., Alexandre cv, A., Alici l, Cy, A., Alkin c, J., Alme aj, T., Alt an, V., Altini ae, S., Altinpinar q, I., Altsybeev dw, C., Alves Garcia Prado dm, C., Andrei by, A., Andronic cq, V., Anguelov cm, J., Anielski az, T., Anticˇic ́ cr, F., Antinori db, P., Antonioli cy, L., Aphecetche df, H., Appelshäuser ax, N., Arbor br, S., Arcelli z, N., Armesto p, R., Arnaldi de, T., Aronsson ec, I. C., Arsene u, Cq, M., Arslandok ax, A., Augustinus ah, R., Averbeck cq, T. C., Awes ce, M. D., Azmi r, Cj, M., Bach an, A., Badalà da, Y. W., Baek ao, Bq, S., Bagnasco de, R., Bailhache ax, V., Bairathi cl, R., Bala ck, A., Baldisseri n, F., Baltasar Dos Santos Pedrosa ah, J., Bán bf, R. C., Baral bh, R., Barbera aa, F., Barile ae, G. G., Barnaföldi eb, L. S., Barnby cv, V., Barret bq, J., Bartke dj, M., Basile z, N., Bastid bq, S., Basu dx, B., Bathen az, G., Batigne df, B., Batyunya bm, P. C., Batzing u, C., Baumann ax, I. G., Bearden ca, H., Beck ax, C., Bedda cn, N. K., Behera a, I., Belikov ba, F., Bellini z, R., Bellwied do, E., Belmont Moreno bk, G., Bencedi eb, S., Beole y, I., Berceanu by, A., Bercuci by, Y., Berdnikov cf, D., Berenyi eb, M. E., Berger di, A. A. E., Bergognon df, R. A., Bertens bd, D., Berzano y, L., Betev ah, A., Bhasin ck, A. K., Bhati ch, B., Bhattacharjee ap, J., Bhom dt, L., Bianchi y, N., Bianchi b, C., Bianchin bd, J., Bielcˇík al, J., Bielcˇíková cd, A., Bilandzic ca, S., Bjelogrlic bd, F., Blanco j, D., Blau ct, C., Blume ax, F., Bock bu, Cm, F. V., Boehmer di, A., Bogdanov bw, H., Bøggild ca, M., Bogolyubsky bb, L., Boldizsár eb, M., Bombara am, J., Book ax, H., Borel n, A., Borissov cp, Ea, J., Bornschein an, F., Bossú bl, M., Botje cb, E., Botta y, S., Böttger aw, P., Braun Munzinger cq, M., Bregant dm, Df, T., Breitner aw, T. A., Broker ax, T. A., Browning co, M., Broz ak, E., Bruna de, G. E., Bruno ae, D., Budnikov c, H., Buesching ax, S., Bufalino de, P., Buncic ah, O., Busch cm, Z., Buthelezi bl, D., Caffarri ab, X., Cai g, H., Caines ec, A., Caliva bd, E., Calvo Villar cw, V., Canoa Roman ah, F., Carena ah, W., Carena ah, F., Carminati ah, A., Casanova Díaz b, J., Castillo Castellanos n, E. A. R., Casula w, V., Catanescu by, C., Cavicchioli ah, C., Ceballos Sanchez i, J., Cepila al, P., Cerello de, B., Chang dp, S., Chapeland ah, J. L., Charvet n, S., Chattopadhyay dx, S., Chattopadhyay cu, M., Cherney cg, C., Cheshkov dv, B., Cheynis dv, V., Chibante Barroso ah, D. D., Chinellato do, Dn, P., Chochula ah, M., Chojnacki ca, S., Choudhury dx, P., Christakoglou cb, C. H., Christensen ca, P., Christiansen af, T., Chujo dt, S. U., Chung cp, C., Cicalo cz, L., Cifarelli l, Z, F., Cindolo cy, J., Cleymans cj, F., Colamaria ae, D., Colella ae, A., Collu w, M., Colocci z, G., Conesa Balbastre br, Z., Conesa del Valle av, Ah, M. E., Connors ec, G., Contin x, J. G., Contreras k, T. M., Cormier ce, Y., Corrales Morales y, P., Cortese ad, I., Cortés Maldonado b, M. R., Cosentino bu, Dm, F., Costa ah, P., Crochet bq, R., Cruz Albino k, E., Cuautle bj, L., Cunqueiro b, A., Dainese db, R., Dang g, A., Danu bi, D., Das cu, I., Das av, K., Das cu, S., Das d, A., Dash dn, S., Dash a, S., De dx, H., Delagrange df, A., Deloff bx, E., Dénes eb, G., D’Erasmo ae, G. O. V., de Barros dm, A., De Caro l, Ac, G., de Cataldo cx, J., de Cuveland an, A., De Falco w, D., De Gruttola ac, L, N., De Marco de, S., De Pasquale ac, R., de Rooij bd, M. A., Diaz Corchero j, T., Dietel az, R., Divià ah, D., Di Bari ae, S., Di Liberto dc, A., Di Mauro ah, P., Di Nezza b, Ø., Djuvsland q, A., Dobrin bd, T., Dobrowolski bx, D., Domenicis Gimenez dm, B., Dönigus ax, O., Dordic u, S., Dorheim di, A. K., Dubey dx, A., Dubla bd, L., Ducroux dv, P., Dupieux bq, A. K., Dutta Majumdar cu, D., Elia cx, H., Engel aw, B., Erazmus ah, H. A., Erdal aj, D., Eschweiler an, B., Espagnon av, M., Estienne df, S., Esumi dt, D., Evans cv, S., Evdokimov bb, G., Eyyubova u, D., Fabris db, J., Faivre br, D., Falchieri z, A., Fantoni b, M., Fasel cm, D., Fehlker q, L., Feldkamp az, D., Felea bi, A., Feliciello de, G., Feofilov dw, J., Ferencei cd, A., Fernández Téllez b, E. G., Ferreiro p, A., Ferretti y, A., Festanti ab, J., Figiel dj, M. A. S., Figueredo dm, Dq, S., Filchagin c, D., Finogeev bc, F. M., Fionda ae, E. M., Fiore ae, E., Floratos ci, M., Floris ah, S., Foertsch bl, P., Foka cq, S., Fokin ct, A., Francescon ab, U., Frankenfeld cq, U., Fuchs ah, C., Furget br, M., Fusco Girard ac, J. J., Gaardhøje ca, M., Gagliardi y, M., Gallio y, D. R., Gangadharan, Bu, P., Ganoti ce, Ci, C., Garabatos cq, E., Garcia Solis m, C., Gargiulo ah, I., Garishvili bv, J., Gerhard an, M., Germain df, A., Gheata ah, M., Gheata ah, Bi, B., Ghidini ae, P., Ghosh dx, S. K., Ghosh d, P., Gianotti b, P., Giubellino ah, E., Gladysz Dziadus dj, P., Glässel cm, R., Gomez k, P., González Zamora j, S., Gorbunov an, L., Görlich dj, S., Gotovac dh, L. K., Graczykowski dz, R., Grajcarek cm, A., Grelli bd, A., Grigoras ah, C., Grigoras ah, V., Grigoriev bw, A., Grigoryan a, S., Grigoryan bm, B., Grinyov c, N., Grion dd, J. F., Grosse Oetringhaus ah, J. Y., Grossiord dv, R., Grosso ah, F., Guber bc, R., Guernane br, B., Guerzoni z, M., Guilbaud dv, K., Gulbrandsen ca, H., Gulkanyan a, T., Gunji d, A., Gupta ck, R., Gupta ck, K. H., Khan o, R., Haake az, Ø., Haaland q, C., Hadjidakis av, M., Haiduc bi, H., Hamagaki d, G., Hamar eb, L. D., Hanratty cv, A., Hansen ca, J. W., Harris ec, H., Hartmann an, A., Harton m, D., Hatzifotiadou cy, S., Hayashi d, A., Hayrapetyan ah, A, S. T., Heckel ax, M., Heide az, H., Helstrup aj, A., Herghelegiu by, G., Herrera Corral k, B. A., Hess ag, K. F., Hetland aj, B., Hicks ec, B., Hippolyte ba, J., Hladky bg, P., Hristov ah, M., Huang q, T. J., Humanic, D., Hutter an, D. S., Hwang t, J. C., Ianigro dv, R., Ilkaev c, I., Ilkiv bx, M., Inaba dt, E., Incani w, G. M., Innocenti y, C., Ionita ah, M., Ippolitov ct, M., Irfan r, M., Ivanov cq, V., Ivanov cf, O., Ivanytskyi c, A., Jachołkowski aa, C., Jahnke dm, H. J., Jang bo, M. A., Janik dz, P. H. S. Y., Jayarathna do, S., Jena a, Do, R. T., Jimenez Bustamante bj, P. G., Jones cv, H., Jung ao, A., Jusko cv, S., Kalcher an, P., Kalinak bf, A., Kalweit ah, J., Kamin ax, J. H., Kang ed, V., Kaplin bw, S., Kar dx, A., Karasu Uysal bp, O., Karavichev bc, T., Karavicheva bc, E., Karpechev bc, U., Kebschull aw, R., Keidel ee, B., Ketzer ai, Di, M. M., Khan r, P., Khan cu, S. A., Khan dx, A., Khanzadeev cf, Y., Kharlov bb, B., Kileng aj, B., Kim ed, D. W., Kim bo, Ao, D. J., Kim dp, J. S., Kim ao, M., Kim ao, M., Kim ed, S., Kim t, T., Kim ed, S., Kirsch an, I., Kisel an, S., Kiselev be, A., Kisiel dz, G., Kiss eb, J. L., Klay f, J., Klein cm, C., Klein Bösing az, A., Kluge ah, M. L., Knichel cq, A. G., Knospe dk, C., Kobdaj dg, M. K., Köhler cq, T., Kollegger an, A., Kolojvari dw, V., Kondratiev dw, N., Kondratyeva bw, A., Konevskikh bc, V., Kovalenko dw, M., Kowalski dj, S., Kox br, G., Koyithatta Meethaleveedu a, J., Kral dp, I., Králik bf, F., Kramer ax, A., Kravcˇáková am, M., Krelina al, M., Kretz an, M., Krivda cv, Bf, F., Krizek cd, Aq, M., Krus al, E., Kryshen cf, M., Krzewicki cq, V., Kucˇera cd, Y., Kucheriaev ct, T., Kugathasan ah, C., Kuhn ba, P. G., Kuijer cb, I., Kulakov ax, J., Kumar a, P., Kurashvili bx, A., Kurepin bc, A. B., Kurepin bc, A., Kuryakin c, S., Kushpil cd, V., Kushpil cd, M. J., Kweon cm, Au, Y., Kwon ed, P., Ladron de Guevara bj, C., Lagana Fernandes dm, I., Lakomov av, R., Langoy dy, C., Lara aw, A., Lardeux df, A., Lattuca y, S. L., La Pointe bd, P., La Rocca aa, G. R., Lee cv, I., Legrand ah, J., Lehnert ax, R. C., Lemmon cc, M., Lenhardt cq, V., Lenti cx, E., Leogrande bd, M., Leoncino y, I., León Monzón dl, P., Lévai eb, S., Li bq, G, J., Lien dy, Q, R., Lietava cv, S., Lindal u, V., Lindenstruth an, C., Lippmann cq, M. A., Lisa, H. M., Ljunggren af, D. F., Lodato bd, P. I., Loenne q, V. R., Loggins ea, V., Loginov bw, D., Lohner cm, C., Loizides bu, X., Lopez bq, E., López Torres i, X. G., Lu cm, P., Luettig ax, M., Lunardon ab, J., Luo g, C., Luzzi ah, A. M., Gago cw, P. M., Jacobs bu, R., Ma ec, A., Maevskaya bc, M., Mager ah, D. P., Mahapatra bh, A., Maire cm, Ba, M., Malaev cf, I., Maldonado Cervantes bj, L., Malinina bm, D., Mal’Kevich be, P., Malzacher cq, A., Mamonov c, L., Manceau de, V., Manko ct, F., Manso bq, V., Manzari cx, M., Marchisone bq, Y, J., Mareš bg, A., Margotti cy, A., Marín cq, C., Markert ah, Dk, M., Marquard ax, I., Martashvili dr, N. A., Martin cq, P., Martinengo ah, M. I., Martínez b, G., Martínez García df, J., Martin Blanco df, Y., Martynov c, A., Mas df, S., Masciocchi cq, M., Masera y, A., Masoni cz, L., Massacrier df, A., Mastroserio ae, A., Matyja dj, C., Mayer dj, J., Mazer dr, R., Mazumder at, M. A., Mazzoni dc, F., Meddi v, A., Menchaca Rocha bk, J., Mercado Pérez cm, M., Meres ak, Y., Miake dt, K., Mikhaylov be, Bm, L., Milano ah, J., Milosevic u, A., Mischke bd, A. N., Mishra at, D., Mis ́kowiec cq, C. M., Mitu bi, J., Mlynarz ea, B., Mohanty dx, Bz, L., Molnar ba, L., Montaño Zetina k, E., Montes j, M., Morando ab, D. A., Moreira De Godoy dm, S., Moretto ab, A., Morreale dp, A., Morsch ah, V., Muccifora b, E., Mudnic dh, S., Muhuri dx, M., Mukherjee dx, H., Müller ah, M. G., Munhoz dm, S., Murray cj, Bl, L., Musa ah, J., Musinsky bf, B. K., Nandi a, R., Nania cy, E., Nappi cx, C., Nattrass dr, T. K., Nayak dx, S., Nazarenko c, A., Nedosekin be, M., Nicassio cq, M., Niculescu ah, B. S., Nielsen ca, S., Nikolaev ct, S., Nikulin ct, V., Nikulin cf, B. S., Nilsen cg, F., Noferini l, P., Nomokonov bm, G., Nooren bd, A., Nyanin ct, A., Nyatha a, J., Nystrand q, H., Oeschler cm, Ay, S., Oh ec, S. K., Oh bn, Ao, 6, A., Okatan bp, L., Olah eb, J., Oleniacz dz, A. C., Oliveira Da Silva dm, J., Onderwaater cq, C., Oppedisano de, A., Ortiz Velasquez af, A., Oskarsson af, J., Otwinowski cq, K., Oyama cm, Y., Pachmayer cm, M., Pachr al, P., Pagano ac, G., Paic ́ bj, F., Painke an, C., Pajares p, S. K., Pal dx, A., Palmeri da, D., Pant a, V., Papikyan a, G. S., Pappalardo da, W. J., Park cq, A., Passfeld az, D. I., Patalakha bb, V., Paticchio cx, B., Paul cu, T., Pawlak dz, T., Peitzmann bd, H., Pereira Da Costa n, E., Pereira De Oliveira Filho dm, D., Peresunko ct, C. E., Pérez Lara cb, W., Peryt dz, A., Pesci cy, Y., Pestov e, V., Petrácˇek al, M., Petran al, M., Petris by, M., Petrovici by, C., Petta aa, M., Pikna ak, P., Pillot df, O., Pinazza ah, L., Pinsky do, D. B., Piyarathna do, M., Planinic cr, Du, M., Płoskon ́ bu, J., Pluta dz, S., Pochybova eb, P. L. M., Podesta Lerma dl, M. G., Poghosyan ah, Cg, E. H. O., Pohjoisaho aq, B., Polichtchouk bb, N., Poljak cr, A., Pop by, S., Porteboeuf Houssais bq, J., Porter bu, V., Pospisil al, B., Potukuchi ck, S. K., Prasad ea, D, R., Preghenella cy, F., Prino de, C. A., Pruneau ea, I., Pshenichnov bc, G., Puddu w, P., Pujahari ea, As, V., Punin c, J., Putschke ea, H., Qvigstad u, A., Rachevski dd, S., Raha d, J., Rak dp, A., Rakotozafindrabe n, L., Ramello ad, R., Raniwala cl, S., Raniwala cl, S. S., Räsänen aq, B. T., Rascanu ax, D., Rathee ch, A. W., Rauf o, V., Razazi w, K. F., Read dr, J. S., Real br, K., Redlich bx, R. J., Reed ec, A., Rehman q, P., Reichelt ax, M., Reicher bd, F., Reidt ah, R., Renfordt ax, A. R., Reolon b, A., Reshetin bc, F., Rettig an, J. P., Revol ah, K., Reygers cm, V., Riabov cf, R. A., Ricci bt, T., Richert af, M., Richter u, P., Riedler ah, W., Riegler ah, F., Riggi aa, A., Rivetti de, E., Rocco bd, M., Rodríguez Cahuantzi b, A., Rodriguez Manso cb, K., Røed u, E., Rogochaya bm, S., Rohni ck, D., Rohr an, D., Röhrich q, R., Romita dq, Cc, F., Ronchetti b, L., Ronflette df, P., Rosnet bq, S., Rossegger ah, A., Rossi ah, A., Roy at, C., Roy ba, P., Roy cu, A. J., Rubio Montero j, R., Russo y, E., Ryabinkin ct, Y., Ryabov cf, A., Rybicki dj, S., Sadovsky bb, K., Šafarˇík ah, B., Sahlmuller ax, R., Sahoo at, P. K., Sahu bh, J., Saini dx, C. A., Salgado p, J., Salzwedel, S., Sambyal ck, V., Samsonov cf, X., Sanchez Castro ba, Bj, F. J., Sánchez Rodríguez dl, L., Šándor bf, A., Sandoval bk, M., Sano dt, G., Santagati aa, D., Sarkar dx, E., Scapparone cy, F., Scarlassara ab, R. P., Scharenberg co, C., Schiaua by, R., Schicker cm, C., Schmidt cq, H. R., Schmidt ag, S., Schuchmann ax, J., Schukraft ah, M., Schulc al, T., Schuster ec, Y., Schutz ah, K., Schwarz cq, K., Schweda cq, G., Scioli z, E., Scomparin de, P. A., Scott cv, R., Scott dr, G., Segato ab, J. E., Seger cg, I., Selyuzhenkov cq, J., Seo cp, E., Serradilla j, Bk, A., Sevcenco bi, A., Shabetai df, G., Shabratova bm, R., Shahoyan ah, A., Shangaraev bb, N., Sharma dr, Bh, S., Sharma ck, K., Shigaki ar, K., Shtejer y, Y., Sibiriak ct, S., Siddhanta cz, T., Siemiarczuk bx, D., Silvermyr ce, C., Silvestre br, G., Simatovic du, R., Singaraju dx, R., Singh ck, S., Singha bz, Dx, V., Singhal dx, B. C., Sinha dx, T., Sinha cu, B., Sitar ak, M., Sitta ad, T. B., Skaali u, K., Skjerdal q, R., Smakal al, N., Smirnov ec, R. J. M., Snellings bd, C., Søgaard af, R., Soltz bv, J., Song cp, M., Song ed, F., Soramel ab, S., Sorensen dr, M., Spacek al, I., Sputowska dj, M., Spyropoulou Stassinaki ci, B. K., Srivastava co, J., Stachel cm, I., Stan bi, G., Stefanek bx, M., Steinpreis, E., Stenlund af, G., Steyn bl, J. H., Stiller cm, D., Stocco df, M., Stolpovskiy bb, P., Strmen ak, A. A. P., Suaide dm, M. A., Subieta Vasquez y, T., Sugitate ar, C., Suire av, M., Suleymanov o, R., Sultanov be, M., Šumbera cd, T., Susa cr, T. J. M., Symons bu, A., Szanto de Toledo dm, I., Szarka ak, A., Szczepankiewicz ah, M., Szymanski dz, J., Takahashi dn, M. A., Tangaro ae, J. D., Tapia Takaki av, A., Tarantola Peloni ax, A., Tarazona Martinez ah, A., Tauro ah, G., Tejeda Muñoz b, A., Telesca ah, C., Terrevoli ae, A., Ter Minasyan ct, Bw, J., Thäder cq, D., Thomas bd, R., Tieulent dv, A. R., Timmins do, A., Toia db, Ax, H., Torii d, V., Trubnikov c, W. H., Trzaska dp, T., Tsuji d, A., Tumkin c, R., Turrisi db, T. S., Tveter u, J., Ulery ax, K., Ullaland q, J., Ulrich aw, A., Uras dv, G. L., Usai w, M., Vajzer cd, M., Vala bf, L., Valencia Palomo bq, Av, S., Vallero y, P., Vande Vyvre ah, L., Vannucci bt, J. W., Van Hoorne ah, M., van Leeuwen bd, A., Vargas b, R., Varma a, M., Vasileiou ci, A., Vasiliev ct, V., Vechernin dw, M., Veldhoen bd, M., Venaruzzo x, E., Vercellin y, S., Vergara Limón b, R., Vernet h, M., Verweij ea, L., Vickovic dh, G., Viesti ab, J., Viinikainen dp, Z., Vilakazi bl, O., Villalobos Baillie cv, A., Vinogradov ct, L., Vinogradov dw, Y., Vinogradov c, T., Virgili ac, Y. P., Viyogi dx, A., Vodopyanov bm, M. A., Völkl cm, K., Voloshin be, S. A., Voloshin ea, G., Volpe ah, B., von Haller ah, I., Vorobyev dw, D., Vranic cq, J., Vrláková am, B., Vulpescu bq, A., Vyushin c, B., Wagner q, J., Wagner cq, V., Wagner al, M., Wang g, Y., Wang cm, D., Watanabe dt, M., Weber do, J. P., Wessels az, U., Westerhoff az, J., Wiechula ag, J., Wikne u, M., Wilde az, G., Wilk bx, J., Wilkinson cm, M. C. S., Williams cy, B., Windelband cm, M., Winn cm, C., Xiang g, C. G., Yaldo ea, Y., Yamaguchi d, H., Yang n, Bd, P., Yang g, S., Yang q, S., Yano ar, S., Yasnopolskiy ct, J., Yi cp, Z., Yin g, I. K., Yoo cp, I., Yushmanov ct, Zaccolo ca, V., C., Zach al, A., Zaman o, C., Zampolli cy, S., Zaporozhets bm, A., Zarochentsev dw, P., Závada bg, N., Zaviyalov c, H., Zbroszczyk dz, I. S., Zgura bi, M., Zhalov cf, F., Zhang g, H., Zhang g, X., Zhang bq, G, Bu, Y., Zhang g, C., Zhao u, D., Zhou g, F., Zhou g, Y., Zhou bd, H., Zhu g, J., Zhu g, X., Zhu g, A., Zichichi l, A., Zimmermann cm, M. B., Zimmermann ah, Az, G., Zinovjev c, Y., Zoccarato dv, M., Zynovyev c, M., Zyzak, and Contin, Giacomo
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Relativistic heavy ion collisions ,Quarkonium ,J/ψ suppression ,Quark gluon plasma ,Experimental results ,Relativistic heavy ion collision - Abstract
The inclusive J/ψ nuclear modification factor (RAA) in Pb–Pb collisions at √sNN = 2.76 TeV has been measured by ALICE as a function of centrality in the e+e− decay channel at mid-rapidity (|y| < 0.8) and as a function of centrality, transverse momentum and rapidity in the μ+μ− decay channel at forward-rapidity (2.5 < y < 4). The J/ψ yields measured in Pb–Pb are suppressed compared to those in pp collisions scaled by the number of binary collisions. The RAA integrated over a centrality range corresponding to 90% of the inelastic Pb–Pb cross section is 0.72±0.06(stat.)±0.10(syst.) at mid-rapidity and 0.58 ± 0.01(stat.) ± 0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAA are measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/ψ yield originates from charm quark (re)combination in the deconfined partonic medium.
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- 2014
4. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial
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Paz-Ares, L, de Marinis, F, Dediu, M, Thomas, M, Pujol, J, Bidoli, P, Molinier, O, Sahoo, T, Laack, E, Reck, M, Corral, J, Melemed, S, John, W, Chouaki, N, Zimmermann, A, Visseren-Grul, C, Gridelli, C, Pujol, JL, Sahoo, TP, Zimmermann, AH, Paz-Ares, L, de Marinis, F, Dediu, M, Thomas, M, Pujol, J, Bidoli, P, Molinier, O, Sahoo, T, Laack, E, Reck, M, Corral, J, Melemed, S, John, W, Chouaki, N, Zimmermann, A, Visseren-Grul, C, Gridelli, C, Pujol, JL, Sahoo, TP, and Zimmermann, AH
- Abstract
Background: Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin. Methods: In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction pemetrexed (500 mg/m 2) plus cisplatin (75 mg/m 2) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either pemetrexed (500 mg/m 2 every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373. Findings: Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation mainten
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- 2012
5. PCN84 VALIDATION OF THE EUROQOL EQ-5D IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA (RR MCL)
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Cuyun Carter, G, primary, Liepa, AM, additional, Zimmermann, AH, additional, and Morschhauser, F, additional
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- 2009
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6. 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
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Koji Kawai, Satoshi Nagamori, Katherine M Bell-McGuinn, Cristiano Ferrario, Wen Pin Su, Isabel Syndikus, Aude Flechon, Georgios Gakis, Timothy Dudley Clay, Leticia Vazquez Cortés, Ronald de Wit, Florence Joly, Bozena Sikora-Kupis, Sergio Bracarda, Astra M. Liepa, Annemie Rutten, Daniel P. Petrylak, Su Peng Yeh, Annamaria Zimmermann, Sameera R. Wijayawardana, Mutsushi Kawakita, Siobhan Ng, Thean Hsiang Tan, Chikara Ohyama, Yu Jung Kim, Yuriy Golovko, Dimitrios Mavroudis, Jian Ri Li, Reinoud J. B. Blaisse, Mustafa Erman, Francesca Russo, Catherine Becht, Anghel Adrian Udrea, Robert Huddart, Syed A. Hussain, Fransiscus L.G. Erdkamp, Satoshi Fukasawa, Francesco Massari, Motohide Uemura, Boris Alekseev, Irfan Cicin, Se Hoon Park, Marcello Tucci, Lajos Géczi, Maureen J.B. Aarts, Yu Li Su, Fumimasa Fukuta, Hyo Jin Lee, Wolfgang Schultze-Seemann, Alexandra Drakaki, Hakan Harputluoglu, Xavier Garcia del Muro, Santhanam Sundar, Avivit Peer, Herlinde Dumez, William E. Lawler, Juan Ignacio Delgado Mignorance, Naveed Sarwar, Jeanny B. Aragon-Ching, Benjamin T. Herms, Fredrik Laestadius, Nobuaki Matsubara, Ivan Sinielnikov, Cora N. Sternberg, Hiroyuki Nishiyama, Piotr Tomczak, Brigitte Laguerre, Rebecca R. Hozak, Vasilis Karavasilis, Christina A. Schwentner, Hiroyuki Tsunemori, Masayoshi Nagata, Igor Bondarenko, Andrea Necchi, Yen Chuan Ou, Scott T. Tagawa, Constance Thibault, Richard A. Walgren, Akira Yokomizo, Evan Y. Yu, Alejo Rodriguez-Vida, Sufia Safina, Ulka N. Vaishampayan, János Révész, Aristotelis Bamias, Jae-Lyun Lee, Chien Liang Lin, Thomas W. Flaig, Roman Fomkin, Petr Alexandrovich Karlov, Joanna Wojcik-Tomaszewska, Junichi Inokuchi, Wataru Obara, Haralambos Kalofonos, John D. Hainsworth, Marc-Oliver Grimm, Thomas Eugene Lowe, Pablo Gajate Borau, Simon J. Crabb, Lisa Sengeloev, Junji Yonese, Simon Chowdhury, Elizabeth Jane Hovey, Daniel Castellano, Peter Istvan Acs, Chia-Chi Lin, Claudia Lorena Urzua Flores, Jean-Pascal Machiels, Kim N. Chi, Takahiro Osawa, Nobuo Shinohara, Daniel Kejzman, Günter Niegisch, David Sarid, Yuksel Urun, Yun Gyoo Lee, Oday Hamid, Alina Amalia Herzal, Michael Schenker, Eli Rosenbaum, Enrique Grande, Raya Leibowitz-Amit, Naoto Miyajima, Michiel S. van der Heijden, Shinichi Yamashita, Susanna Yee Shan Cheng, Kazuo Nishimura, Sun Young Rha, Thomas Powles, Hasan Şenol Coşkun, Jens Bedke, Ivor J. Percent, Christos Papandreou, James K. Schwarz, Masafumi Oyama, Giorgio V. Scagliotti, Chong-Xian Pan, Yoshihiko Tomita, Giampaolo Tortora, Stéphane Culine, Suet Lai Shirley Wong, Andrey Semenov, Jennifer L. Cultrera, Niels Viggo Jensen, Michael Stöckle, Katsuyoshi Hashine, Medical Oncology, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Centre du cancer, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), Petrylak, Dp, de Wit, R, Chi, Kn, Drakaki, A, Sternberg, Cn, Nishiyama, H, Castellano, D, Hussain, Sa, Flechon, A, Bamias, A, Yu, Ey, van der Heijden, M, Matsubara, N, Alekseev, B, Necchi, A, Geczi, L, Ou, Yc, Coskun, H, Su, Wp, Bedke, J, Gakis, G, Percent, Ij, Lee, Jl, Tucci, M, Semenov, A, Laestadius, F, Peer, A, Tortora, G, Safina, S, del Muro, Xg, Rodriguez-Vida, A, Cicin, I, Harputluoglu, H, Tagawa, St, Vaishampayan, U, Aragon-Ching, Jb, Hamid, O, Liepa, Am, Wijayawardana, S, Russo, F, Walgren, Ra, Zimmermann, Ah, Hozak, Rr, Bell-McGuinn, Km, Powles, T, and Graduate School
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Male ,0301 basic medicine ,MULTICENTER ,Docetaxel ,Gastroenterology ,ANGIOGENESIS ,VINFLUNINE ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Neoplasm Metastasis ,education.field_of_study ,CHEMOTHERAPY ,Middle Aged ,OPEN-LABEL ,Prognosis ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,EXPRESSION ,Urologic Neoplasms ,medicine.medical_specialty ,BEVACIZUMAB ,Population ,BLADDER-CANCER ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Placebo ,Ramucirumab ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Neoplasm Invasiveness ,education ,Survival rate ,Aged ,Platinum ,Salvage Therapy ,Carcinoma, Transitional Cell ,business.industry ,medicine.disease ,ATEZOLIZUMAB ,030104 developmental biology ,ENDOTHELIAL GROWTH-FACTOR ,business ,Febrile neutropenia ,Follow-Up Studies - Abstract
Background Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonistplus 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/m 2 (60 mg/m 2 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. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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- 2020
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7. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial
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Daniel P Petrylak, Ronald de Wit, Kim N Chi, Alexandra Drakaki, Cora N Sternberg, Hiroyuki Nishiyama, Daniel Castellano, Syed Hussain, Aude Fléchon, Aristotelis Bamias, Evan Y Yu, Michiel S van der Heijden, Nobuaki Matsubara, Boris Alekseev, Andrea Necchi, Lajos Géczi, Yen-Chuan Ou, Hasan Senol Coskun, Wen-Pin Su, Miriam Hegemann, Ivor J Percent, Jae-Lyun Lee, Marcello Tucci, Andrey Semenov, Fredrik Laestadius, Avivit Peer, Giampaolo Tortora, Sufia Safina, Xavier Garcia del Muro, Alejo Rodriguez-Vida, Irfan Cicin, Hakan Harputluoglu, Ryan C Widau, Astra M Liepa, Richard A Walgren, Oday Hamid, Annamaria H Zimmermann, Katherine M Bell-McGuinn, Thomas Powles, Suet-Lai Shirley Wong, Thean Hsiang Tan, Elizabeth Jane Hovey, Timothy Dudley Clay, Siobhan Su Wan Ng, Annemie Rutten, Jean-Pascal Machiels, Herlinde Dumez, Susanna Yee-Shan Cheng, Kim Nguyen Chi, Cristiano Ferrario, Lisa Sengeloev, Niels Viggo Jensen, Constance Thibault, Brigitte Laguerre, Florence Joly, Aude Flechon, Stéphane Culine, Catherine Becht, Günter Niegisch, Michael Stöckle, Marc-Oliver Grimm, Georgios Gakis, Wolfgang Schultze-Seemann, Haralambos Kalofonos, Dimitrios Mavroudis, Christos Papandreou, Vasilis Karavasilis, Janos Révész, Lajos Geczi, Eli Rosenbaum, Raya Leibowitz-Amit, Daniel Kejzman, David Sarid, Giorgio Vittorio Scagliotti, Sergio Bracarda, Francesco Massari, Takahiro Osawa, Naoto Miyajima, Nobuo Shinohara, Fumimasa Fukuta, Chikara Ohyama, Wataru Obara, Shinichi Yamashita, Yoshihiko Tomita, Koji Kawai, Satoshi Fukasawa, Masafumi Oyama, Junji Yonese, Masayoshi Nagata, Motohide Uemura, Kazuo Nishimura, Mutsushi Kawakita, Hiroyuki Tsunemori, Katsuyoshi Hashine, Junichi Inokuchi, Akira Yokomizo, Satoshi Nagamori, Hyo Jin Lee, Se Hoon Park, Sun Young Rha, Yu Jung Kim, Yun-Gyoo Lee, Leticia Vazquez Cortés, Claudia Lorena Urzua Flores, Reinoud J B Blaisse, Fransiscus L G Erdkamp, Maureen J B Aarts, Joanna Wojcik-Tomaszewska, Piotr Tomczak, Bozena Sikora-Kupis, Michael Schenker, Alina Amalia Herzal, Anghel Adrian Udrea, Petr Karlov, Sufia Z Safina, Roman Fomkin, Enrique Grande Pulido, F Xavier García Del Muro, Juan Ignacio Delgado Mignorance, Daniel Castellano Gauna, Alejo Rodríguez-Vida, Yu-Li Su, Chien-Liang Lin, Chia-Chi Lin, Su-Peng Yeh, Irfan Çiçin, Mustafa Erman, Yuksel Urun, Yurii Golovko, Igor Bondarenko, Ivan Sinielnikov, Simon Crabb, Isabel Syndikus, Robert Huddart, Santhanam Sundar, Simon Chowdhury, Naveed Sarwar, Thomas Flaig, Chong Xian Pan, Daniel Petrylak, James Schwarz, Ivor Percent, Jennifer Cultrera, John Hainsworth, Benjamin Herms, William Lawler, Thomas Lowe, Scott Tagawa, Jeanny Aragon-Ching, Ulka Vaishampayan, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'oncologie médicale, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), Petrylak, Dp, de Wit, R, Chi, Kn, Drakaki, A, Sternberg, Cn, Nishiyama, H, Castellano, D, Hussain, S, Flechon, A, Bamias, A, Yu, Ey, van der Heijden, M, Matsubara, N, Alekseev, B, Necchi, A, Geczi, L, Ou, Yc, Coskun, H, Su, Wp, Hegemann, M, Percent, Ij, Lee, Jl, Tucci, M, Semenov, A, Laestadius, F, Peer, A, Tortora, G, Safina, S, del Muro, Xg, Rodriguez-Vida, A, Cicin, I, Harputluoglu, H, Widau, Rc, Liepa, Am, Walgren, Ra, Hamid, O, Zimmermann, Ah, Bell-McGuinn, Km, Powles, T, and Medical Oncology
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0301 basic medicine ,Male ,Internationality ,medicine.medical_treatment ,Phases of clinical research ,Docetaxel ,Kaplan-Meier Estimate ,Gastroenterology ,2ND-LINE THERAPY ,0302 clinical medicine ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,ramucirab ,Medicine (all) ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,OPEN-LABEL ,Prognosis ,Neoadjuvant Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Taxoids ,medicine.drug ,Adult ,medicine.medical_specialty ,Metastatic Urothelial Carcinoma ,Urology ,Locally advanced ,BLADDER-CANCER ,Placebo ,Antibodies, Monoclonal, Humanized ,Risk Assessment ,Ramucirumab ,Antibodies ,Disease-Free Survival ,Double blind ,II TRIAL ,03 medical and health sciences ,LUNG-CANCER ,Aged ,Carcinoma, Transitional Cell ,Double-Blind Method ,Humans ,Neoplasm Invasiveness ,Neoplasm Staging ,Proportional Hazards Models ,Survival Analysis ,Urinary Bladder Neoplasms ,Internal medicine ,BREAST-CANCER ,In patient ,Adverse effect ,Platinum ,Chemotherapy ,FACTOR RECEPTOR-2 ,Settore MED/06 - ONCOLOGIA MEDICA ,business.industry ,Carcinoma ,TRANSITIONAL-CELL-CARCINOMA ,Surgery ,Discontinuation ,Regimen ,Ramucirumab, docetaxel ,030104 developmental biology ,ENDOTHELIAL GROWTH-FACTOR ,Transitional Cell ,business ,FOLLOW-UP - Abstract
Summary Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population. 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 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m 2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96–4·47] vs 2·76 months [2·60–2·96]; hazard ratio [HR] 0·757, 95% CI 0·607–0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8–30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4–18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1–2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Funding Eli Lilly and Company.
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- 2017
8. Exposure-response relationship of ramucirumab in RANGE, a randomized phase III trial in advanced urothelial carcinoma refractory to platinum therapy.
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de Wit R, Powles T, Castellano D, Necchi A, Lee JL, van der Heijden MS, Matsubara N, Bamias A, Fléchon A, Sternberg CN, Drakaki A, Yu EY, Zimmermann AH, Long A, Walgren RA, Gao L, Bell-McGuinn KM, and Petrylak DP
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- Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, Docetaxel, Humans, Platinum therapeutic use, Ramucirumab, Carcinoma, Transitional Cell drug therapy, Urinary Bladder Neoplasms drug therapy
- Abstract
Aims: Patients with advanced urothelial carcinoma (UC) who progress after platinum-based chemotherapy have a poor prognosis, and there is a medical need to improve current treatment options. Ramucirumab plus docetaxel significantly improved progression-free survival but not overall survival (OS) in platinum-refractory advanced UC (RANGE trial; NCT02426125). Here, we report the exposure-response (ER) of ramucirumab plus docetaxel using data from the RANGE trial., Methods: Pharmacokinetic (PK) samples were collected (cycle 1-3, 5, 9 [day 1] and 30 days from treatment discontinuation), and PK data were analysed using population PK (popPK) analysis. The minimum ramucirumab concentration after first dose administration (C
min,1 , or trough concentration immediately prior to the second dose) was derived by popPK analysis and used as the exposure parameter for ER analysis. Cox proportional hazards regression models and matched case-control analyses were used to evaluate the relationship between Cmin,1 and OS. The Cmin,1 relationship with safety was assessed descriptively., Results: Several poor prognostic factors (ECOG 1, haemoglobin concentration <100 g/L, presence of liver metastases) appeared more frequently in the lower exposure quartiles, suggesting a possible disease-PK interaction. A significant association was identified between Cmin,1 and OS (P = .0108). Higher exposure quartiles were associated with longer survival and smaller hazard ratios compared to placebo. No new exposure-safety trends were observed within the exposure range (ramucirumab 10 mg/kg once every 3 weeks)., Conclusions: This prespecified ER analyses suggests a positive relationship between efficacy and ramucirumab exposure, with an imbalance associated with disease prognostic factors. Further investigation may elucidate a possible disease-PK relationship., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2022
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9. RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non-Small Cell Lung Cancer.
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Nakagawa K, Nadal E, Garon EB, Nishio M, Seto T, Yamamoto N, Park K, Shih JY, Paz-Ares L, Frimodt-Moller B, Zimmermann AH, Wijayawardana S, Visseren-Grul C, and Reck M
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- Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, ErbB Receptors genetics, Erlotinib Hydrochloride, Humans, Mutation, Protein Kinase Inhibitors therapeutic use, Ramucirumab, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Purpose: In EGFR-mutated metastatic non-small cell lung cancer (NSCLC), outcomes from EGFR tyrosine kinase inhibitors have differed historically by mutation type present, with lower benefit reported in patients with ex21L858R versus ex19del mutations. We investigated if EGFR-activating mutation subtypes impact treatment outcomes in the phase III RELAY study. Associations between EGFR mutation type and preexisting co-occurring and treatment-emergent genetic alterations were also explored., Patients and Methods: Patients with metastatic NSCLC, an EGFR ex19del or ex21L858R mutation, and no central nervous system metastases were randomized (1:1) to erlotinib (150 mg/day) with either ramucirumab (10 mg/kg; RAM+ERL) or placebo (PBO+ERL), every 2 weeks, until RECIST v1.1-defined progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary and exploratory endpoints included overall response rate (ORR), duration of response (DOR), PFS2, time-to-chemotherapy (TTCT), safety, and next-generation sequencing analyses., Results: Patients with ex19del and ex21L858R mutations had similar clinical characteristics and comutational profiles. One-year PFS rates for ex19del patients were 74% for RAM+ERL versus 54% for PBO+ERL; for ex21L858R rates were 70% (RAM+ERL) versus 47% (PBO+ERL). Similar treatment benefits (ORR, DOR, PFS2, and TTCT) were observed in RAM+ERL-treated patients with ex19del and ex21L858R. Baseline TP53 comutation was associated with superior outcomes for RAM+ERL in both ex19del and ex21L858R subgroups. EGFR T790M mutation rate at progression was similar between treatment arms and by mutation type., Conclusions: RAM+ERL provided significant clinical benefit for both EGFR ex19del and ex21L858R NSCLC, supporting this regimen as suitable for patients with either of these EGFR mutation types., (©2021 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2021
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10. Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy.
- Author
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Garon EB, Scagliotti GV, Gautschi O, Reck M, Thomas M, Iglesias Docampo L, Kalofonos H, Kim JH, Gans S, Brustugun OT, Orlov SV, Cuyun Carter G, Zimmermann AH, Oton AB, Alexandris E, Lee P, Wolff K, Stefaniak VJ, Socinski MA, and Pérol M
- Subjects
- Antibodies, Monoclonal, Humanized pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Disease Progression, Docetaxel pharmacology, Female, Humans, Neoplasm Staging, Ramucirumab, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Docetaxel therapeutic use, Lung Neoplasms drug therapy, Platinum therapeutic use
- Abstract
Introduction: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease. Front-line therapy may affect responses to subsequent treatment regimens, thus influencing second-line therapy decision making. In the randomised phase 3 REVEL study, second-line ramucirumab plus docetaxel (ram+doc) versus docetaxel (doc) improved survival of patients with metastatic NSCLC. We explore efficacy, safety and quality-of-life (QoL) in REVEL based on front-line therapy., Methods: Patients were grouped by specific front-line therapy received. Overall survival (OS), progression-free survival (PFS), objective response rate, safety and QoL were assessed descriptively. Kaplan-Meier estimation and Cox proportional hazards modelling were used; frequencies reported in percentages., Results: Baseline characteristics of 1253 patients were generally well balanced between treatment arms within each front-line therapy subgroup. For patients with non-squamous disease (n=912), induction therapies included platinum-based chemotherapy plus a taxane (n=227; 25%) or pemetrexed (n=449; 49%), with (n=172; 19%) or without bevacizumab. For patients with squamous disease (n=328), induction therapies included platinum-based chemotherapy plus gemcitabine (n=176; 54%) or a taxane (n=69; 21%). A highly selected subgroup (n=127; 14%) received pemetrexed continuation maintenance therapy. Ram+doc improved median OS and PFS versus doc across front-line therapy subgroups, as reflected by HRs ranging from 0.78 to 0.91 and 0.66 to 0.92, respectively, similar to results in the overall intention-to-treat cohort (HRs: 0.86 and 0.76, respectively). High-grade treatment-emergent adverse events of special interest (including neutropenia, febrile neutropenia, leucopenia and hypertension) were generally higher in ram+doc-treated patients relative to doc-treated patients regardless of front-line therapy. No clear differences in safety or QoL were seen across front-line therapy subgroups; outcomes were consistent with those reported in the overall intention-to-treat cohort., Conclusions: Results of this exploratory analysis suggest that second-line ram+doc may be effective regardless of prior treatment with platinum-based chemotherapy plus a taxane, pemetrexed, gemcitabine or bevacizumab. Overall, ram+doc is clinically beneficial across a wide range of patients with metastatic NSCLC who have progressed after various front-line therapies., Trial Registration Number: NCT01168973., Competing Interests: Competing interests: The following authors declared conflicts of interests. GCC, AHZ, ABO, PL, KW, and VJS are full-time employees and stockowners of Eli Lilly and Company. EA is a former employee and stockowner of Eli Lilly and Company. EBG has received honoraria from Dracen and EMD Serono, and his institution has received research funding from AstraZeneca, Bristol Myers Squibb, Merck, Eli Lilly and Company, Novartis, Genentech, Dynavax, Iovance, Mirati, and Neon. GVS has received honoraria from Eli Lilly and Company, AstraZeneca, Clovis Oncology, Regeneron, Novartis, Merck Sharp and Dohme, Pfizer, and Roche and has served on the speaker’s bureaus of Eli Lilly and Company, AstraZeneca, Merck Sharp and Dohme, and Novartis. MR has received honoraria for lectures from and functions in an advisory/consulting role for Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Hoffman-La Roche, Merck, Novartis, and Pfizer. MT has received Advisory Board honoraria from AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Eli Lilly and Company, Merck Sharp and Dohme, Novartis, Roche, Takeda; speaker’s honoraria from Eli Lilly and Company, Merck Sharp and Dohme, Takeda; research funding from AstraZeneca, Bristol Myers Squibb, Celgene, Roche; and travel grants from Bristol Myers Squibb, Boehringer, Merck Sharp and Dohme, and Novartis. HK has received reimbursement for meeting expenses and/or has functioned in an advisory/consultancy role for Eli Lilly and Company, Genesis Pharma, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche and has received reimbursement for meeting expenses from Enorasis. J-HK serves in an advisory/consultancy role for and his institution has received grant funding for clinical trials from Eli Lilly and Company, including during the conduct of this study, and from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Roche. OTB has received honoraria from Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim (for research funding and advisory/consultancy role), GlaxoSmithKline (for research funding), Merck (for advisory/consultancy role), Novartis, Pfizer, and Roche (for research funding). MP has received honoraria for speaking, advisory and consultancy roles for Eli Lilly and Company., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)
- Published
- 2020
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11. East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL).
- Author
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Park K, Kim JH, Cho EK, Kang JH, Shih JY, Zimmermann AH, Lee P, Alexandris E, Puri T, and Orlando M
- Subjects
- Adult, Aged, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, Asian People, Carcinoma, Non-Small-Cell Lung pathology, Disease Progression, Disease-Free Survival, Docetaxel, Double-Blind Method, Female, Humans, Male, Middle Aged, Neoplasm Staging, Placebos, Platinum administration & dosage, Taxoids adverse effects, Treatment Outcome, Ramucirumab, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Taxoids administration & dosage
- Abstract
Purpose: REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported., Materials and Methods: Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate., Results: In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m
2 , n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2 ) and 54.5% versus 38.5% (60 mg/m2 ). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2 ) and 0% versus 7.7% (60 mg/m2 )., Conclusion: Results of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety., Competing Interests: Jin-Hyoung Kang and Jin-Yuan Shih received honoraria from Eli Lilly and Company. Annamaria Hayden Zimmermann, Pablo Lee, Ekaterine Alexandris, Tarun Puri, and Mauro Orlando are employees of Eli Lilly & Company. Tarun Puri and Mauro Orlando hold stock with Eli Lilly and Company. All remaining authors have declared no conflicts of interest. This study was sponsored by Eli Lilly and Company.- Published
- 2016
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12. PARAMOUNT: Descriptive subgroup analyses of final overall survival for the phase III study of maintenance pemetrexed versus placebo following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.
- Author
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Reck M, Paz-Ares LG, de Marinis F, Molinier O, Sahoo TP, Laack E, John W, Zimmermann AH, Visseren-Grul C, and Gridelli C
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma mortality, Adenocarcinoma pathology, Aged, Carcinoma, Large Cell drug therapy, Carcinoma, Large Cell mortality, Carcinoma, Large Cell pathology, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Cisplatin administration & dosage, Female, Follow-Up Studies, Glutamates administration & dosage, Guanine administration & dosage, Guanine analogs & derivatives, Humans, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Pemetrexed, Prognosis, Remission Induction, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung mortality, Lung Neoplasms mortality, Maintenance Chemotherapy
- Abstract
Introduction: The PARAMOUNT phase III trial demonstrated that pemetrexed continuation maintenance significantly reduced the risk of disease progression (hazard ratio = 0.62) and death (hazard ratio = 0.78) versus placebo in patients with advanced nonsquamous non-small-cell lung cancer. To further understand the survival data, descriptive subgroup analyses were undertaken., Methods: Nine hundred thirty-nine patients received induction therapy (four 21-day cycles pemetrexed 500 mg/m and cisplatin 75 mg/m), after which 539 nonprogressing patients with an Eastern Cooperative Oncology Group performance status (PS) of 0/1 were randomized (2:1) to maintenance pemetrexed (500 mg/m) cycles or placebo until disease progression., Results: Baseline characteristics of patients surviving for longer periods were comparable to patients surviving shorter periods, suggesting overall survival (OS) benefit for all subgroups of patients on maintenance therapy. An examination of type and severity of induction adverse events also found no association with survival duration. Response to induction (tumor response versus stable disease) was not determinate of pemetrexed maintenance OS outcome as assessed by waterfall plot and scattergrams and by the distribution of patients among various OS intervals. The length of the interval before beginning maintenance therapy (<7 days versus ≥7/≤30 days) also did not impact the survival results. PS, a known prognostic factor, was the only baseline characteristic associated with improved OS; however, both PS 0 and PS 1 patients exhibited a survival benefit from pemetrexed maintenance., Conclusions: In PARAMOUNT, the OS benefit was seen across all subgroups. Other than PS, no baseline or clinical parameter clearly identified a subgroup more likely to benefit. Maintenance treatment decisions should be made on an individual basis.
- Published
- 2014
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13. Polymer networks produced by marine diatoms in the northern Adriatic sea.
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Svetličić V, Žutić V, Radić TM, Pletikapić G, Zimmermann AH, and Urbani R
- Subjects
- Gels chemistry, Microscopy, Atomic Force methods, Oceans and Seas, Biopolymers metabolism, Diatoms metabolism, Polysaccharides metabolism
- Abstract
Using high resolution molecular technique of atomic force microscopy, we address the extracellular polymer production of Adriatic diatom Cylindrotheca closterium analyzed at the single cell level and the supramolecular organization of gel phase isolated from the Northern Adriatic macroaggregates. Our results revealed that extracellular polysaccharides freshly produced by marine diatoms can self-assemble directly to form gel network characteristics of the macroscopic gel phase in the natural aquatorium. Based on the experiments performed with isolated polysaccharide fractions of C. closterium and of macroaggregates gel phase, we demonstrated that the polysaccharide self-assembly into gel network can proceed independent of any bacterial mediation or interaction with inorganic particles.
- Published
- 2011
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