학술논문
Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings†
Document Type
Academic Journal
Author
Kubicka, S.; Greil, R.; André, T.; Bennouna, J.; Sastre, J.; Van Cutsem, E.; von Moos, R.; Österlund, P.; Reyes-Rivera, I.; Müller, T.; Makrutzki, M.; Arnold, D.; Andel, J; Balcke, P; Benedicic, B; Eisterer, W; Fridrik, M; Jagdt, B; Keil, F; Kretschmer, A; Krippl, P; Oexle, H; Pecherstorfer, M; Samonigg, H; Schmid, M; Thaler, J; Tinchon, C; Weiss, H.; Arts, J; De Man, M; Demolin, G; Janssens, J; Polus, M.; Benczikova, B; Melichar, B; Prausova, J; Vitek, P.; Andersen, FZ; Jensen, BB; Keldsen, N; Østerlind, K; Vistisen, K.; Elme, A; Magi, A; Ojamaa, K.; Ristamäki, R; Salminen, T.; Ben Abdelghani, M; Bouche, O; Borg, C; Bouhier-Leporrier, K; Breysacher, G; Chone, L; Clavero Fabri, M-C; Deplanque, G; Desseigne, F; Dourthe, L-M; Ezenfis, J; Faroux, R; François, E; Garnier, C; Gaspard, M-H; Hebbar, M; Illory, JF; Kaminsky, M-C; Lecomte, T; Legoux, J-L; Levache, B; Lobry, C; Lotz, J-P; Mabro, M; Manet-Lacombe, S; Manfredi, S; Matysiak Budnik, T; Miglianico, L; Mineur, L; Moullet, I; Naman, H; Nouyrigat, P; Oziel-Taieb, S; Perrier, H; Pezet, D; Philip, J; Pottier, V; Porneuf, M; Ramdani, M; Re, D; Rinaldi, Y; Spaeth, D; Taieb, J; Terrebonne, E; Texereau, P; Thirot Bidault, A; Tournigand, C; Tubiana-Mathieu, N; Vantelon, J-M; Viret, F; Ychou, M.; Bangerter, M; Bertram, ME; Bohnsteen, B; Brinkmann, L; Caca, K; Constantin, C; Cordes, H-J; Dietrich, G; Eggert, J; Engel, E; Fahlke, J; Fensterer, H; Florschütz, A; Folprecht, G; Forstbauer, H; Freier, W; Freund, M; Frickhofen, N; Gäbele, E; Geiler, M; Gieseler, F; Göhler, T; Graeven, U; Groschek, M; Grundeis, M; Hacker, U; Hagen, V; Hebart, HF; Hegewisch-Becker, S; Heike, M; Herrmann, T; Hildebrandt, B; Höffkes, H-G; Hübner, G; Hübner, J; Kettner, E; Kneba, M; Kohnke, JW; Kojouharoff, G; König, C; Kretzschmar, A; Kröning, H; Kürner, K; Lammert, F; Lerchenmüller, C; Lück, A; Meiler, J; Mergenthaler, H-G; Müller, L; Müller-Naendrup, C; Nusch, A; Papke, J; Porschen, R; Rädle, J; Reddemann, C; Ridwelski, K; Riera-Knorrenschild, J; Rudi, J; Schmalenberger, A; Schimanski, C-C; Schlegel, F; Schlichting, C; Schmidt, P; Schmiegel, W; Schmitz, S; Schulze-Bergkamen, H; Schwaner, I; Schwarzer, A; Schwerdtfeger, M; Selbach, J; Sieber, M; Siebler, J; Staib, P; Stauch, M; Steffens, C-C; Stübs, P; Tischendorf, J; Trarbach, T; Tummes, D; Valdix, A-R; Vogel, A; Von Wichert, GPL; Walther, M; Welslau, W; Wilhelm, G; Wobster, H; Wolf, T; Zeigenhagen, N; Zomorodbaksch, B.; Batman, E; Bloemendal, HJ; Kehrer, DFS.; Guren, T; Indrebø, G; Kersten, C; Soerbye, H.; Fragoso, M; Fragoso, R; Mellidez, JC; Sa, A.; Aljobran, A; Darwish, T.; Alonso-Orduna, V; Aparicio, J; Aranda, E; Bosch, C; Galan-Brotons, A; Busquier Hernandez, I; Camara, JC; Campos Cervera, JM; Carlos Garcia Giron, C; Del Prado, PM; Donnay, O; Escudero, P; Falco, E; Gallego Plazas, J; Garcia Alfonso, P; Gonzalez Flores, E; Gravalos, C; Guardeno, R; Juárez, A; Lopez Ladron, A; Losa Gaspa, F; MVicent Vergé, J; Marcuello Gaspar, E; Massuti Sureda, B; Molina, J; Montero, IC; Muñoa, AL; Naranjo, MB; Oruezabal Moreno, MJ; Pachón Olmos, V; Pericay, C; Reina Zoilo, JJ; Rivera, F; Ruiz Casado, A; Safont, MJ; Salud Salvia, A; Tobena, M; Toral, JC; Valenti, V; Valladares Ayerbes, M; Vieitez, JM; Vera, R; Vieitez, JM.; Berglund, A; Fernebro, E.; Hess-Umbricht, V; Pless, M; Popescu, R; Winterhalder, R.
Source
Annals of Oncology. Sep 01, 2013 24(9):2342-2349
Subject
Language
English
ISSN
0923-7534
Abstract
BACKGROUND: ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy. PATIENTS AND METHODS: Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutation-specific Scorpion amplification-refractory mutation system). No adjustment was made for multiplicity; analyses were not powered to detect statistically significant differences. RESULTS: Of 820 patients, 616 (75%) had unambiguous KRAS data; 316 (51%) had KRAS wild-type tumors and 300 (49%) had mutant KRAS tumors. The median progression-free survival (PFS) was 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P < 0.0001; HR = 0.61; 95% confidence interval (CI): 0.49–0.77] for wild-type KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.56–0.89) for mutant KRAS. The median overall survival (OS) was 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.53–0.90) for wild-type KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.71–1.18) for mutant KRAS. In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266). CONCLUSIONS: Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.