Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings

Stefan Kubicka Prof.; R. Greil; T. André; J. Bennouna; J. Sastre; E. Van Cutsem; R. Von Moos; P. Österlund; I. Reyes-Rivera; T. Müller; M. Makrutzki; D. Arnold; 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; F. Z. Andersen; B. B. Jensen; N. Keldsen; K. Østerlind; 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; J. F. 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; M. E. 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; H. F. Hebart; S. Hegewisch-Becker; M. Heike; T. Herrmann; B. Hildebrandt; H. G. Höffkes; G. Hübner; J. Hübner; E. Kettner; M. Kneba; J. W. 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; G. P.L. Von Wichert; M. Walther; W. Welslau; G. Wilhelm; H. Wobster; T. Wolf; N. Zeigenhagen; B. Zomorodbaksch; E. Batman; H. J. Bloemendal; D. F.S. Kehrer; T. Guren; G. Indrebø; C. Kersten; H. Soerbye; M. Fragoso; R. Fragoso; J. C. Mellidez; A. Sa; A. Aljobran; T. Darwish; V. Alonso-Orduna; J. Aparicio; E. Aranda; C. Bosch; A. Galan-Brotons; I. Busquier Hernandez; J. C. Camara; J. M. Campos Cervera; C. Carlos Garcia Giron; P. M. 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. MaVicent Vergé; E. Marcuello Gaspar; B. Massuti Sureda; J. Molina; I. C. Montero; A. L. Muñoa; M. B. Naranjo; M. J. Oruezabal Moreno; V. Pachón Olmos; C. Pericay; J. J. Reina Zoilo; F. Rivera; A. Ruiz Casado; M. J. Safont; A. Salud Salvia; M. Tobena; J. C. Toral; V. Valenti; M. Valladares Ayerbes; J. M. Vieitez; R. Vera; J. M. Vieitez; A. Berglund; E. Fernebro; V. Hess-Umbricht; M. Pless; R. Popescu; R. Winterhalder

doi:10.1093/annonc/mdt231

Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings

Stefan Kubicka Prof., R. Greil, T. André, J. Bennouna, J. Sastre, E. Van Cutsem, R. Von Moos, P. Österlund, I. Reyes-Rivera, T. Müller, M. Makrutzki, D. Arnold, J. Andel, P. Balcke, B. Benedicic, W. Eisterer, M. Fridrik, B. Jagdt, F. Keil, A. KretschmerP. 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, F. Z. Andersen, B. B. Jensen, N. Keldsen, K. Østerlind, 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, J. F. 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, M. E. 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, H. F. Hebart, S. Hegewisch-Becker, M. Heike, T. Herrmann, B. Hildebrandt, H. G. Höffkes, G. Hübner, J. Hübner, E. Kettner, M. Kneba, J. W. 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, G. P.L. Von Wichert, M. Walther, W. Welslau, G. Wilhelm, H. Wobster, T. Wolf, N. Zeigenhagen, B. Zomorodbaksch, E. Batman, H. J. Bloemendal, D. F.S. Kehrer, T. Guren, G. Indrebø, C. Kersten, H. Soerbye, M. Fragoso, R. Fragoso, J. C. Mellidez, A. Sa, A. Aljobran, T. Darwish, V. Alonso-Orduna, J. Aparicio, E. Aranda, C. Bosch, A. Galan-Brotons, I. Busquier Hernandez, J. C. Camara, J. M. Campos Cervera, C. Carlos Garcia Giron, P. M. 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. MaVicent Vergé, E. Marcuello Gaspar, B. Massuti Sureda, J. Molina, I. C. Montero, A. L. Muñoa, M. B. Naranjo, M. J. Oruezabal Moreno, V. Pachón Olmos, C. Pericay, J. J. Reina Zoilo, F. Rivera, A. Ruiz Casado, M. J. Safont, A. Salud Salvia, M. Tobena, J. C. Toral, V. Valenti, M. Valladares Ayerbes, J. M. Vieitez, R. Vera, J. M. Vieitez, A. Berglund, E. Fernebro, V. Hess-Umbricht, M. Pless, R. Popescu, R. Winterhalder

Clinic of Internal Medicine I

99 Citations (Scopus)

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.

Original language	English
Journal	Annals of Oncology
Volume	24
Issue number	9
Pages (from-to)	2342-2349
Number of pages	8
ISSN	0923-7534
DOIs	https://doi.org/10.1093/annonc/mdt231
Publication status	Published - 09.2013

Funding

DA has received consulting fees or honoraria from Roche, Merck, and Amgen and research funding from Roche. TA is a consultant for Roche and Amgen and has received honoraria from Roche, Amgen, and Merck Serono. JB is an advisory board member for and has received honoraria from Roche. SK has received consulting fees/honoraria, travel grants, and payment for lectures including service on speakers bureaus from Roche. MM is an employee of Roche. TM is an employee of Roche Genentech. PÖ has received consulting fees, honoraria, travel grants, or lecturing fees from Roche, Amgen, and Merck, research funding from Roche, and is an advisory board member for Roche, Amgen, Bayer, Sanofi Oncology, and Merck. IR-R is an employee of Roche. JS has received honoraria for consultant or advisory activity from Sanofi-Aventis and Roche. EVC has received research funding from Roche, paid to his institution. RvM is an advisory board member for Roche, Novartis, Merck, Amgen, and Bristol-Myers Squibb and has received an unrestricted research grant from Roche, Amgen, and Merck. RG has no conflict to declare. This study was sponsored by F. Hoffmann-La Roche. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1093/annonc/mdt231

Cite this

Kubicka Prof., 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., ... Winterhalder, R. (2013). Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. Annals of Oncology, 24(9), 2342-2349. https://doi.org/10.1093/annonc/mdt231

@article{f55d73514dc244ada57126c73a631f44,

title = "Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings",

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.",

author = "\{Kubicka Prof.\}, Stefan and R. Greil and T. Andr{\'e} and J. Bennouna and J. Sastre and \{Van Cutsem\}, E. and \{Von Moos\}, R. and P. {\"O}sterlund and I. Reyes-Rivera and T. M{\"u}ller and M. Makrutzki and D. Arnold and J. Andel and P. Balcke and B. Benedicic and W. Eisterer and M. Fridrik and B. Jagdt and F. Keil and A. Kretschmer and P. Krippl and H. Oexle and M. Pecherstorfer and H. Samonigg and M. Schmid and J. Thaler and C. Tinchon and H. Weiss and J. Arts and \{De Man\}, M. and G. Demolin and J. Janssens and M. Polus and B. Benczikova and B. Melichar and J. Prausova and P. Vitek and Andersen, \{F. Z.\} and Jensen, \{B. B.\} and N. Keldsen and K. {\O}sterlind and K. Vistisen and A. Elme and A. Magi and K. Ojamaa and R. Ristam{\"a}ki and T. Salminen and \{Ben Abdelghani\}, M. and O. Bouche and C. Borg and K. Bouhier-Leporrier and G. Breysacher and L. Chone and \{Clavero Fabri\}, \{M. C.\} and G. Deplanque and F. Desseigne and Dourthe, \{L. M.\} and J. Ezenfis and R. Faroux and E. Fran{\c c}ois and C. Garnier and Gaspard, \{M. H.\} and M. Hebbar and Illory, \{J. F.\} and Kaminsky, \{M. C.\} and T. Lecomte and Legoux, \{J. L.\} and B. Levache and C. Lobry and Lotz, \{J. P.\} and M. Mabro and S. Manet-Lacombe and S. Manfredi and \{Matysiak Budnik\}, T. and L. Miglianico and L. Mineur and I. Moullet and H. Naman and P. Nouyrigat and S. Oziel-Taieb and H. Perrier and D. Pezet and J. Philip and V. Pottier and M. Porneuf and M. Ramdani and D. Re and Y. Rinaldi and D. Spaeth and J. Taieb and E. Terrebonne and P. Texereau and \{Thirot Bidault\}, A. and C. Tournigand and N. Tubiana-Mathieu and Vantelon, \{J. M.\} and F. Viret and M. Ychou and M. Bangerter and Bertram, \{M. E.\} and B. Bohnsteen and L. Brinkmann and K. Caca and C. Constantin and Cordes, \{H. J.\} and G. Dietrich and J. Eggert and E. Engel and J. Fahlke and H. Fensterer and A. Florsch{\"u}tz and G. Folprecht and H. Forstbauer and W. Freier and M. Freund and N. Frickhofen and E. G{\"a}bele and M. Gei{\ss}ler and F. Gieseler and T. G{\"o}hler and U. Graeven and M. Groschek and M. Grundeis and U. Hacker and V. Hagen and Hebart, \{H. F.\} and S. Hegewisch-Becker and M. Heike and T. Herrmann and B. Hildebrandt and H{\"o}ffkes, \{H. G.\} and G. H{\"u}bner and J. H{\"u}bner and E. Kettner and M. Kneba and Kohnke, \{J. W.\} and G. Kojouharoff and C. K{\"o}nig and A. Kretzschmar and H. Kr{\"o}ning and K. K{\"u}rner and F. Lammert and C. Lerchenm{\"u}ller and A. L{\"u}ck and J. Meiler and Mergenthaler, \{H. G.\} and L. M{\"u}ller and C. M{\"u}ller-Naendrup and A. Nusch and J. Papke and R. Porschen and J. R{\"a}dle and C. Reddemann and K. Ridwelski and J. Riera-Knorrenschild and J. Rudi and A. Schmalenberger and Schimanski, \{C. C.\} and F. Schlegel and C. Schlichting and P. Schmidt and W. Schmiegel and S. Schmitz and H. Schulze-Bergkamen and I. Schwaner and A. Schwarzer and M. Schwerdtfeger and J. Selbach and M. Sieber and J. Siebler and P. Staib and M. Stauch and Steffens, \{C. C.\} and P. St{\"u}bs and J. Tischendorf and T. Trarbach and D. Tummes and Valdix, \{A. R.\} and A. Vogel and \{Von Wichert\}, \{G. P.L.\} and M. Walther and W. Welslau and G. Wilhelm and H. Wobster and T. Wolf and N. Zeigenhagen and B. Zomorodbaksch and E. Batman and Bloemendal, \{H. J.\} and Kehrer, \{D. F.S.\} and T. Guren and G. Indreb{\o} and C. Kersten and H. Soerbye and M. Fragoso and R. Fragoso and Mellidez, \{J. C.\} and A. Sa and A. Aljobran and T. Darwish and V. Alonso-Orduna and J. Aparicio and E. Aranda and C. Bosch and A. Galan-Brotons and \{Busquier Hernandez\}, I. and Camara, \{J. C.\} and \{Campos Cervera\}, \{J. M.\} and \{Carlos Garcia Giron\}, C. and \{Del Prado\}, \{P. M.\} and O. Donnay and P. Escudero and E. Falco and \{Gallego Plazas\}, J. and \{Garcia Alfonso\}, P. and \{Gonzalez Flores\}, E. and C. Gravalos and R. Guardeno and A. Ju{\'a}rez and \{Lopez Ladron\}, A. and \{Losa Gaspa\}, F. and \{MaVicent Verg{\'e}\}, J. and \{Marcuello Gaspar\}, E. and \{Massuti Sureda\}, B. and J. Molina and Montero, \{I. C.\} and Mu{\~n}oa, \{A. L.\} and Naranjo, \{M. B.\} and \{Oruezabal Moreno\}, \{M. J.\} and \{Pach{\'o}n Olmos\}, V. and C. Pericay and \{Reina Zoilo\}, \{J. J.\} and F. Rivera and \{Ruiz Casado\}, A. and Safont, \{M. J.\} and \{Salud Salvia\}, A. and M. Tobena and Toral, \{J. C.\} and V. Valenti and \{Valladares Ayerbes\}, M. and Vieitez, \{J. M.\} and R. Vera and Vieitez, \{J. M.\} and A. Berglund and E. Fernebro and V. Hess-Umbricht and M. Pless and R. Popescu and R. Winterhalder",

note = "Funding Information: DA has received consulting fees or honoraria from Roche, Merck, and Amgen and research funding from Roche. TA is a consultant for Roche and Amgen and has received honoraria from Roche, Amgen, and Merck Serono. JB is an advisory board member for and has received honoraria from Roche. SK has received consulting fees/honoraria, travel grants, and payment for lectures including service on speakers bureaus from Roche. MM is an employee of Roche. TM is an employee of Roche Genentech. P{\"O} has received consulting fees, honoraria, travel grants, or lecturing fees from Roche, Amgen, and Merck, research funding from Roche, and is an advisory board member for Roche, Amgen, Bayer, Sanofi Oncology, and Merck. IR-R is an employee of Roche. JS has received honoraria for consultant or advisory activity from Sanofi-Aventis and Roche. EVC has received research funding from Roche, paid to his institution. RvM is an advisory board member for Roche, Novartis, Merck, Amgen, and Bristol-Myers Squibb and has received an unrestricted research grant from Roche, Amgen, and Merck. RG has no conflict to declare. Funding Information: This study was sponsored by F. Hoffmann-La Roche. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche.",

year = "2013",

month = sep,

doi = "10.1093/annonc/mdt231",

language = "English",

volume = "24",

pages = "2342--2349",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd",

number = "9",

}

Kubicka Prof., 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, MC, Deplanque, G, Desseigne, F, Dourthe, LM, Ezenfis, J, Faroux, R, François, E, Garnier, C, Gaspard, MH, Hebbar, M, Illory, JF, Kaminsky, MC, Lecomte, T, Legoux, JL, Levache, B, Lobry, C, Lotz, JP, 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, JM, Viret, F, Ychou, M, Bangerter, M, Bertram, ME, Bohnsteen, B, Brinkmann, L, Caca, K, Constantin, C, Cordes, HJ, Dietrich, G, Eggert, J, Engel, E, Fahlke, J, Fensterer, H, Florschütz, A, Folprecht, G, Forstbauer, H, Freier, W, Freund, M, Frickhofen, N, Gäbele, E, Geißler, 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, HG, 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, HG, 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, CC, 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, CC, Stübs, P, Tischendorf, J, Trarbach, T, Tummes, D, Valdix, AR, 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, MaVicent 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 2013, 'Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings', Annals of Oncology, vol. 24, no. 9, pp. 2342-2349. https://doi.org/10.1093/annonc/mdt231

Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. / Kubicka Prof., Stefan; Greil, R.; André, T. et al.
In: Annals of Oncology, Vol. 24, No. 9, 09.2013, p. 2342-2349.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings

AU - Kubicka Prof., Stefan

AU - Greil, R.

AU - André, T.

AU - Bennouna, J.

AU - Sastre, J.

AU - Van Cutsem, E.

AU - Von Moos, R.

AU - Österlund, P.

AU - Reyes-Rivera, I.

AU - Müller, T.

AU - Makrutzki, M.

AU - Arnold, D.

AU - Andel, J.

AU - Balcke, P.

AU - Benedicic, B.

AU - Eisterer, W.

AU - Fridrik, M.

AU - Jagdt, B.

AU - Keil, F.

AU - Kretschmer, A.

AU - Krippl, P.

AU - Oexle, H.

AU - Pecherstorfer, M.

AU - Samonigg, H.

AU - Schmid, M.

AU - Thaler, J.

AU - Tinchon, C.

AU - Weiss, H.

AU - Arts, J.

AU - De Man, M.

AU - Demolin, G.

AU - Janssens, J.

AU - Polus, M.

AU - Benczikova, B.

AU - Melichar, B.

AU - Prausova, J.

AU - Vitek, P.

AU - Andersen, F. Z.

AU - Jensen, B. B.

AU - Keldsen, N.

AU - Østerlind, K.

AU - Vistisen, K.

AU - Elme, A.

AU - Magi, A.

AU - Ojamaa, K.

AU - Ristamäki, R.

AU - Salminen, T.

AU - Ben Abdelghani, M.

AU - Bouche, O.

AU - Borg, C.

AU - Bouhier-Leporrier, K.

AU - Breysacher, G.

AU - Chone, L.

AU - Clavero Fabri, M. C.

AU - Deplanque, G.

AU - Desseigne, F.

AU - Dourthe, L. M.

AU - Ezenfis, J.

AU - Faroux, R.

AU - François, E.

AU - Garnier, C.

AU - Gaspard, M. H.

AU - Hebbar, M.

AU - Illory, J. F.

AU - Kaminsky, M. C.

AU - Lecomte, T.

AU - Legoux, J. L.

AU - Levache, B.

AU - Lobry, C.

AU - Lotz, J. P.

AU - Mabro, M.

AU - Manet-Lacombe, S.

AU - Manfredi, S.

AU - Matysiak Budnik, T.

AU - Miglianico, L.

AU - Mineur, L.

AU - Moullet, I.

AU - Naman, H.

AU - Nouyrigat, P.

AU - Oziel-Taieb, S.

AU - Perrier, H.

AU - Pezet, D.

AU - Philip, J.

AU - Pottier, V.

AU - Porneuf, M.

AU - Ramdani, M.

AU - Re, D.

AU - Rinaldi, Y.

AU - Spaeth, D.

AU - Taieb, J.

AU - Terrebonne, E.

AU - Texereau, P.

AU - Thirot Bidault, A.

AU - Tournigand, C.

AU - Tubiana-Mathieu, N.

AU - Vantelon, J. M.

AU - Viret, F.

AU - Ychou, M.

AU - Bangerter, M.

AU - Bertram, M. E.

AU - Bohnsteen, B.

AU - Brinkmann, L.

AU - Caca, K.

AU - Constantin, C.

AU - Cordes, H. J.

AU - Dietrich, G.

AU - Eggert, J.

AU - Engel, E.

AU - Fahlke, J.

AU - Fensterer, H.

AU - Florschütz, A.

AU - Folprecht, G.

AU - Forstbauer, H.

AU - Freier, W.

AU - Freund, M.

AU - Frickhofen, N.

AU - Gäbele, E.

AU - Geißler, M.

AU - Gieseler, F.

AU - Göhler, T.

AU - Graeven, U.

AU - Groschek, M.

AU - Grundeis, M.

AU - Hacker, U.

AU - Hagen, V.

AU - Hebart, H. F.

AU - Hegewisch-Becker, S.

AU - Heike, M.

AU - Herrmann, T.

AU - Hildebrandt, B.

AU - Höffkes, H. G.

AU - Hübner, G.

AU - Hübner, J.

AU - Kettner, E.

AU - Kneba, M.

AU - Kohnke, J. W.

AU - Kojouharoff, G.

AU - König, C.

AU - Kretzschmar, A.

AU - Kröning, H.

AU - Kürner, K.

AU - Lammert, F.

AU - Lerchenmüller, C.

AU - Lück, A.

AU - Meiler, J.

AU - Mergenthaler, H. G.

AU - Müller, L.

AU - Müller-Naendrup, C.

AU - Nusch, A.

AU - Papke, J.

AU - Porschen, R.

AU - Rädle, J.

AU - Reddemann, C.

AU - Ridwelski, K.

AU - Riera-Knorrenschild, J.

AU - Rudi, J.

AU - Schmalenberger, A.

AU - Schimanski, C. C.

AU - Schlegel, F.

AU - Schlichting, C.

AU - Schmidt, P.

AU - Schmiegel, W.

AU - Schmitz, S.

AU - Schulze-Bergkamen, H.

AU - Schwaner, I.

AU - Schwarzer, A.

AU - Schwerdtfeger, M.

AU - Selbach, J.

AU - Sieber, M.

AU - Siebler, J.

AU - Staib, P.

AU - Stauch, M.

AU - Steffens, C. C.

AU - Stübs, P.

AU - Tischendorf, J.

AU - Trarbach, T.

AU - Tummes, D.

AU - Valdix, A. R.

AU - Vogel, A.

AU - Von Wichert, G. P.L.

AU - Walther, M.

AU - Welslau, W.

AU - Wilhelm, G.

AU - Wobster, H.

AU - Wolf, T.

AU - Zeigenhagen, N.

AU - Zomorodbaksch, B.

AU - Batman, E.

AU - Bloemendal, H. J.

AU - Kehrer, D. F.S.

AU - Guren, T.

AU - Indrebø, G.

AU - Kersten, C.

AU - Soerbye, H.

AU - Fragoso, M.

AU - Fragoso, R.

AU - Mellidez, J. C.

AU - Sa, A.

AU - Aljobran, A.

AU - Darwish, T.

AU - Alonso-Orduna, V.

AU - Aparicio, J.

AU - Aranda, E.

AU - Bosch, C.

AU - Galan-Brotons, A.

AU - Busquier Hernandez, I.

AU - Camara, J. C.

AU - Campos Cervera, J. M.

AU - Carlos Garcia Giron, C.

AU - Del Prado, P. M.

AU - Donnay, O.

AU - Escudero, P.

AU - Falco, E.

AU - Gallego Plazas, J.

AU - Garcia Alfonso, P.

AU - Gonzalez Flores, E.

AU - Gravalos, C.

AU - Guardeno, R.

AU - Juárez, A.

AU - Lopez Ladron, A.

AU - Losa Gaspa, F.

AU - MaVicent Vergé, J.

AU - Marcuello Gaspar, E.

AU - Massuti Sureda, B.

AU - Molina, J.

AU - Montero, I. C.

AU - Muñoa, A. L.

AU - Naranjo, M. B.

AU - Oruezabal Moreno, M. J.

AU - Pachón Olmos, V.

AU - Pericay, C.

AU - Reina Zoilo, J. J.

AU - Rivera, F.

AU - Ruiz Casado, A.

AU - Safont, M. J.

AU - Salud Salvia, A.

AU - Tobena, M.

AU - Toral, J. C.

AU - Valenti, V.

AU - Valladares Ayerbes, M.

AU - Vieitez, J. M.

AU - Vera, R.

AU - Vieitez, J. M.

AU - Berglund, A.

AU - Fernebro, E.

AU - Hess-Umbricht, V.

AU - Pless, M.

AU - Popescu, R.

AU - Winterhalder, R.

N1 - Funding Information: DA has received consulting fees or honoraria from Roche, Merck, and Amgen and research funding from Roche. TA is a consultant for Roche and Amgen and has received honoraria from Roche, Amgen, and Merck Serono. JB is an advisory board member for and has received honoraria from Roche. SK has received consulting fees/honoraria, travel grants, and payment for lectures including service on speakers bureaus from Roche. MM is an employee of Roche. TM is an employee of Roche Genentech. PÖ has received consulting fees, honoraria, travel grants, or lecturing fees from Roche, Amgen, and Merck, research funding from Roche, and is an advisory board member for Roche, Amgen, Bayer, Sanofi Oncology, and Merck. IR-R is an employee of Roche. JS has received honoraria for consultant or advisory activity from Sanofi-Aventis and Roche. EVC has received research funding from Roche, paid to his institution. RvM is an advisory board member for Roche, Novartis, Merck, Amgen, and Bristol-Myers Squibb and has received an unrestricted research grant from Roche, Amgen, and Merck. RG has no conflict to declare. Funding Information: This study was sponsored by F. Hoffmann-La Roche. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche.

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84883381780

U2 - 10.1093/annonc/mdt231

DO - 10.1093/annonc/mdt231

M3 - Journal articles

C2 - 23852309

AN - SCOPUS:84883381780

SN - 0923-7534

VL - 24

SP - 2342

EP - 2349

JO - Annals of Oncology

JF - Annals of Oncology

IS - 9

ER -

Bevacizumab plus chemotherapy continued beyond first progression in patients withmetastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings

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