Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings
S Kubicka, R Greil, T André, J Bennouna, J Sastre, E Van Cutsem, R von Moos, P Osterlund, I Reyes-Rivera, T Müller, M Makrutzki, D Arnold, ML18147 study investigators including AIO, GERCOR, FFCD, UNICANCER GI, TTD, BGDO, GEMCAD, and AGMT groups, J Andel, P Balcke, B Benedicic, W Eisterer, M Fridrik, B Jagdt, F Keil, A Kretschmer, P Krippl, H Oexle, M Pecherstorfer, H Samonigg, M Schmid, J Thaler, C Tinchon, H Weiss, J Arts, M De Man, G Demolin, J Janssens, M Polus, B Benczikova, B Melichar, J Prausova, P Vitek, Fz Andersen, Bb Jensen, N Keldsen, K Osterlind, K Vistisen, A Elme, A Magi, K Ojamaa, R Ristamäki, T Salminen, M Ben Abdelghani, O Bouche, C Borg, K Bouhier-Leporrier, G Breysacher, L Chone, M-C Clavero Fabri, G Deplanque, F Desseigne, L-M Dourthe, J Ezenfis, R Faroux, E François, C Garnier, M-H Gaspard, M Hebbar, Jf Illory, M-C Kaminsky, T Lecomte, J-L Legoux, B Levache, C Lobry, J-P Lotz, M Mabro, S Manet-Lacombe, S Manfredi, T Matysiak Budnik, L Miglianico, L Mineur, I Moullet, H Naman, P Nouyrigat, S Oziel-Taieb, H Perrier, D Pezet, J Philip, V Pottier, M Porneuf, M Ramdani, D Re, Y Rinaldi, D Spaeth, J Taieb, E Terrebonne, P Texereau, A Thirot Bidault, C Tournigand, N Tubiana-Mathieu, J-M Vantelon, F Viret, M Ychou, M Bangerter, Me Bertram, B Bohnsteen, L Brinkmann, K Caca, C Constantin, H-J Cordes, G Dietrich, J Eggert, E Engel, J Fahlke, H Fensterer, A Florschütz, G Folprecht, H Forstbauer, W Freier, M Freund, N Frickhofen, E Gäbele, M Geißler, F Gieseler, T Göhler, U Graeven, M Groschek, M Grundeis, U Hacker, V Hagen, Hf Hebart, S Hegewisch-Becker, M Heike, T Herrmann, B Hildebrandt, H-G Höffkes, G Hübner, J Hübner, E Kettner, M Kneba, Jw Kohnke, G Kojouharoff, C König, A Kretzschmar, H Kröning, K Kürner, F Lammert, C Lerchenmüller, A Lück, J Meiler, H-G Mergenthaler, L Müller, C Müller-Naendrup, A Nusch, J Papke, R Porschen, J Rädle, C Reddemann, K Ridwelski, J Riera-Knorrenschild, J Rudi, A Schmalenberger, C-C Schimanski, F Schlegel, C Schlichting, P Schmidt, W Schmiegel, S Schmitz, H Schulze-Bergkamen, I Schwaner, A Schwarzer, M Schwerdtfeger, J Selbach, M Sieber, J Siebler, P Staib, M Stauch, C-C Steffens, P Stübs, J Tischendorf, T Trarbach, D Tummes, A-R Valdix, A Vogel, Gpl Von Wichert, M Walther, W Welslau, G Wilhelm, H Wobster, T Wolf, N Zeigenhagen, B Zomorodbaksch, E Batman, Hj Bloemendal, Dfs Kehrer, T Guren, G Indrebø, C Kersten, H Soerbye, M Fragoso, R Fragoso, Jc Mellidez, A Sa, A Aljobran, T Darwish, V Alonso-Orduna, J Aparicio, E Aranda, C Bosch, A Galan-Brotons, I Busquier Hernandez, Jc Camara, Jm Campos Cervera, C Carlos Garcia Giron, Pm Del Prado, O Donnay, P Escudero, E Falco, J Gallego Plazas, P Garcia Alfonso, E Gonzalez Flores, C Gravalos, R Guardeno, A Juárez, A Lopez Ladron, F Losa Gaspa, J M Vicent Vergé, E Marcuello Gaspar, B Massuti Sureda, J Molina, Ic Montero, Al Muñoa, Mb Naranjo, Mj Oruezabal Moreno, V Pachón Olmos, C Pericay, Jj Reina Zoilo, F Rivera, A Ruiz Casado, Mj Safont, A Salud Salvia, M Tobena, Jc Toral, V Valenti, M Valladares Ayerbes, Jm Vieitez, R Vera, Jm Vieitez, A Berglund, E Fernebro, V Hess-Umbricht, M Pless, R Popescu, R Winterhalder, S Kubicka, R Greil, T André, J Bennouna, J Sastre, E Van Cutsem, R von Moos, P Osterlund, I Reyes-Rivera, T Müller, M Makrutzki, D Arnold, ML18147 study investigators including AIO, GERCOR, FFCD, UNICANCER GI, TTD, BGDO, GEMCAD, and AGMT groups, J Andel, P Balcke, B Benedicic, W Eisterer, M Fridrik, B Jagdt, F Keil, A Kretschmer, P Krippl, H Oexle, M Pecherstorfer, H Samonigg, M Schmid, J Thaler, C Tinchon, H Weiss, J Arts, M De Man, G Demolin, J Janssens, M Polus, B Benczikova, B Melichar, J Prausova, P Vitek, Fz Andersen, Bb Jensen, N Keldsen, K Osterlind, K Vistisen, A Elme, A Magi, K Ojamaa, R Ristamäki, T Salminen, M Ben Abdelghani, O Bouche, C Borg, K Bouhier-Leporrier, G Breysacher, L Chone, M-C Clavero Fabri, G Deplanque, F Desseigne, L-M Dourthe, J Ezenfis, R Faroux, E François, C Garnier, M-H Gaspard, M Hebbar, Jf Illory, M-C Kaminsky, T Lecomte, J-L Legoux, B Levache, C Lobry, J-P Lotz, M Mabro, S Manet-Lacombe, S Manfredi, T Matysiak Budnik, L Miglianico, L Mineur, I Moullet, H Naman, P Nouyrigat, S Oziel-Taieb, H Perrier, D Pezet, J Philip, V Pottier, M Porneuf, M Ramdani, D Re, Y Rinaldi, D Spaeth, J Taieb, E Terrebonne, P Texereau, A Thirot Bidault, C Tournigand, N Tubiana-Mathieu, J-M Vantelon, F Viret, M Ychou, M Bangerter, Me Bertram, B Bohnsteen, L Brinkmann, K Caca, C Constantin, H-J Cordes, G Dietrich, J Eggert, E Engel, J Fahlke, H Fensterer, A Florschütz, G Folprecht, H Forstbauer, W Freier, M Freund, N Frickhofen, E Gäbele, M Geißler, F Gieseler, T Göhler, U Graeven, M Groschek, M Grundeis, U Hacker, V Hagen, Hf Hebart, S Hegewisch-Becker, M Heike, T Herrmann, B Hildebrandt, H-G Höffkes, G Hübner, J Hübner, E Kettner, M Kneba, Jw Kohnke, G Kojouharoff, C König, A Kretzschmar, H Kröning, K Kürner, F Lammert, C Lerchenmüller, A Lück, J Meiler, H-G Mergenthaler, L Müller, C Müller-Naendrup, A Nusch, J Papke, R Porschen, J Rädle, C Reddemann, K Ridwelski, J Riera-Knorrenschild, J Rudi, A Schmalenberger, C-C Schimanski, F Schlegel, C Schlichting, P Schmidt, W Schmiegel, S Schmitz, H Schulze-Bergkamen, I Schwaner, A Schwarzer, M Schwerdtfeger, J Selbach, M Sieber, J Siebler, P Staib, M Stauch, C-C Steffens, P Stübs, J Tischendorf, T Trarbach, D Tummes, A-R Valdix, A Vogel, Gpl Von Wichert, M Walther, W Welslau, G Wilhelm, H Wobster, T Wolf, N Zeigenhagen, B Zomorodbaksch, E Batman, Hj Bloemendal, Dfs Kehrer, T Guren, G Indrebø, C Kersten, H Soerbye, M Fragoso, R Fragoso, Jc Mellidez, A Sa, A Aljobran, T Darwish, V Alonso-Orduna, J Aparicio, E Aranda, C Bosch, A Galan-Brotons, I Busquier Hernandez, Jc Camara, Jm Campos Cervera, C Carlos Garcia Giron, Pm Del Prado, O Donnay, P Escudero, E Falco, J Gallego Plazas, P Garcia Alfonso, E Gonzalez Flores, C Gravalos, R Guardeno, A Juárez, A Lopez Ladron, F Losa Gaspa, J M Vicent Vergé, E Marcuello Gaspar, B Massuti Sureda, J Molina, Ic Montero, Al Muñoa, Mb Naranjo, Mj Oruezabal Moreno, V Pachón Olmos, C Pericay, Jj Reina Zoilo, F Rivera, A Ruiz Casado, Mj Safont, A Salud Salvia, M Tobena, Jc Toral, V Valenti, M Valladares Ayerbes, Jm Vieitez, R Vera, Jm Vieitez, A Berglund, E Fernebro, V Hess-Umbricht, M Pless, R Popescu, R Winterhalder
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.
Trial registration: ClinicalTrials.gov NCT00700102.
Keywords: KRAS mutation status; bevacizumab; chemotherapy; colorectal cancer.
Source: PubMed