The Role of Anti-Angiogenics in Pre-Treated Metastatic BRAF-Mutant Colorectal Cancer: A Pooled Analysis

被引:13
作者
Gelsomino, Fabio [1 ]
Casadei-Gardini, Andrea [1 ]
Rossini, Daniele [2 ]
Boccaccino, Alessandra [2 ]
Masi, Gianluca [2 ]
Cremolini, Chiara [2 ]
Spallanzani, Andrea [1 ]
Viola, Massimo Giuseppe [3 ]
Garajova, Ingrid [4 ]
Salati, Massimiliano [1 ]
Elia, Maria Teresa [5 ]
Caputo, Francesco [1 ]
Santini, Chiara [1 ]
Falcone, Alfredo [2 ]
Cascinu, Stefano [6 ]
Tamburini, Emiliano [5 ]
机构
[1] Univ Modena & Reggio Emilia, Div Oncol, Dept Hematol & Oncol, I-4121 Modena, Italy
[2] Univ Pisa, Dept Translat Res & New Technol Med, Med Oncol Unit, Azienda Osped Univ Pisana, I-56121 Pisa, Italy
[3] Card G Panico Hosp Tricase, Dept Surg, I-73039 Tricase, Italy
[4] Univ Hosp Parma, Med Oncol Unit, I-43121 Parma, Italy
[5] Card G Panico Hosp Tricase, Dept Med Oncol, I-73039 Tricase, Italy
[6] Univ Vita Salute, San Raffaele Hosp IRCCS, Dept Med Oncol, I-20019 Milan, Italy
关键词
colorectal cancer; BRAF mutation; anti-angiogenics; chemotherapy; MSI-H; FOLFOXIRI PLUS BEVACIZUMAB; 1ST-LINE TREATMENT; MUTATION STATUS; OPEN-LABEL; STAGE-II; INHIBITION; SURVIVAL; COLON; OXALIPLATIN; THERAPY;
D O I
10.3390/cancers12041022
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. FOLFOXIRI plus Bevacizumab is one of the most frequently used first-line treatments for patients with BRAF-mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated BRAF-mutant CRC. Methods. We monitored patients in randomized, controlled studies who had advanced CRC and were undergoing second-line chemotherapy in addition to utilizing Bevacizumab, Ramucirumab or Aflibercept treatments. These data were pooled together with the data and results of BRAF-mutant patients enrolled in two phase III trials (TRIBE and TRIBE-2 study), who had been treated with second-line treatment both with or without Bevacizumab. Overall survival (OS), in relation to BRAF mutational status, was the primary focus. Results. Pooled analysis included 129 patients. Anti-angiogenics were found to have a significant advantage over the placebo in terms of OS (HR 0.50, 95%CI 0.29-0.85) (p = 0.01). Conclusions. Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated BRAF-mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option.
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页数:9
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共 37 条
[1]   Global patterns and trends in colorectal cancer incidence and mortality [J].
Arnold, Melina ;
Sierra, Monica S. ;
Laversanne, Mathieu ;
Soerjomataram, Isabelle ;
Jemal, Ahmedin ;
Bray, Freddie .
GUT, 2017, 66 (04) :683-691
[2]   Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial [J].
Bennouna, Jaafar ;
Sastre, Javier ;
Arnold, Dirk ;
Osterlund, Pia ;
Greil, Richard ;
Van Cutsem, Eric ;
von Moos, Roger ;
Maria Vieitez, Jose ;
Bouche, Olivier ;
Borg, Christophe ;
Steffens, Claus-Christoph ;
Alonso-Orduna, Vicente ;
Schlichting, Christoph ;
Reyes-Rivera, Irmarie ;
Bendahmane, Belguendouz ;
Andre, Thierry ;
Kubicka, Stefan .
LANCET ONCOLOGY, 2013, 14 (01) :29-37
[3]   EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib [J].
Corcoran, Ryan B. ;
Ebi, Hiromichi ;
Turke, Alexa B. ;
Coffee, Erin M. ;
Nishino, Michiya ;
Cogdill, Alexandria P. ;
Brown, Ronald D. ;
Della Pelle, Patricia ;
Dias-Santagata, Dora ;
Hung, Kenneth E. ;
Flaherty, Keith T. ;
Piris, Adriano ;
Wargo, Jennifer A. ;
Settleman, Jeffrey ;
Mino-Kenudson, Mari ;
Engelman, Jeffrey A. .
CANCER DISCOVERY, 2012, 2 (03) :227-235
[4]   FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials [J].
Cremolini, C. ;
Loupakis, F. ;
Masi, G. ;
Lonardi, S. ;
Granetto, C. ;
Mancini, M. L. ;
Chiara, S. ;
Moretto, R. ;
Rossini, D. ;
Vitello, S. ;
Allegrini, G. ;
Tonini, G. ;
Bergamo, F. ;
Tomasello, G. ;
Ronzoni, M. ;
Buonadonna, A. ;
Bustreo, S. ;
Barbara, C. ;
Boni, L. ;
Falcone, A. .
ANNALS OF ONCOLOGY, 2016, 27 (05) :843-849
[5]   FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study [J].
Cremolini, Chiara ;
Loupakis, Fotios ;
Antoniotti, Carlotta ;
Lupi, Cristiana ;
Sensi, Elisa ;
Lonardi, Sara ;
Mezi, Silvia ;
Tomasello, Gianluca ;
Ronzoni, Monica ;
Zaniboni, Alberto ;
Tonini, Giuseppe ;
Carlomagno, Chiara ;
Allegrini, Giacomo ;
Chiara, Silvana ;
D'Amico, Mauro ;
Granetto, Cristina ;
Cazzaniga, Marina ;
Boni, Luca ;
Fontanini, Gabriella ;
Falcone, Alfredo .
LANCET ONCOLOGY, 2015, 16 (13) :1306-1315
[6]   Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial [J].
Dummer, Reinhard ;
Ascierto, Paolo A. ;
Gogas, Helen J. ;
Arance, Ana ;
Mandala, Mario ;
Liszkay, Gabriella ;
Garbe, Claus ;
Schadendorf, Dirk ;
Krajsova, Ivana ;
Gutzmer, Ralf ;
Chiarion-Sileni, Vanna ;
Dutriaux, Caroline ;
de Groot, Jan Willem B. ;
Yamazaki, Naoya ;
Loquai, Carmen ;
Moutouh-de Parseval, Laure A. ;
Pickard, Michael D. ;
Sandor, Victor ;
Robert, Caroline ;
Flaherty, Keith T. .
LANCET ONCOLOGY, 2018, 19 (05) :603-615
[7]   The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients [J].
Farina-Sarasqueta, A. ;
van Lijnschoten, G. ;
Moerland, E. ;
Creemers, G. -J. ;
Lemmens, V. E. P. P. ;
Rutten, H. J. T. ;
van den Brule, A. J. C. .
ANNALS OF ONCOLOGY, 2010, 21 (12) :2396-2402
[8]   Inhibition of Mutated, Activated BRAF in Metastatic Melanoma [J].
Flaherty, Keith T. ;
Puzanov, Igor ;
Kim, Kevin B. ;
Ribas, Antoni ;
McArthur, Grant A. ;
Sosman, Jeffrey A. ;
O'Dwyer, Peter J. ;
Lee, Richard J. ;
Grippo, Joseph F. ;
Nolop, Keith ;
Chapman, Paul B. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (09) :809-819
[9]   Bevacizumab Beyond First Progression Is Associated With Prolonged Overall Survival in Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study (BRiTE) [J].
Grothey, Axel ;
Sugrue, Mary M. ;
Purdie, David M. ;
Dong, Wei ;
Sargent, Daniel ;
Hedrick, Eric ;
Kozloff, Mark .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (33) :5326-5334
[10]   Impact of primary tumour location and RAS/BRAF mutational status in metastatic colorectal cancer treated with first-line regimens containing oxaliplatin and bevacizumab: Prognostic factors from the AIO KRK0207 first-line and maintenance therapy trial [J].
Hegewisch-Becker, Susanna ;
Noepel-Duennebacke, Stefanie ;
Hinke, Axel ;
Graeven, Ullrich ;
Reinacher-Schick, Anke ;
Hertel, Jan ;
Lerchenmueller, Christian A. ;
Killing, Birgitta ;
Depenbusch, Reinhard ;
Al-Batran, Salah-Eddin ;
Lange, Thoralf ;
Dietrich, Georg ;
Tannapfel, Andrea ;
Arnold, Dirk .
EUROPEAN JOURNAL OF CANCER, 2018, 101 :105-113