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Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies

2014; Elsevier BV; Volume: 25; Issue: 11 Linguagem: Inglês

10.1093/annonc/mdu389

1569-8041

Teresa Morán, Jia Wei, Manuel Cobo, Xiaoping Qian, Manuel Dómine, Zhengyun Zou, Isabel Bover, Lei Wang, Mariano Provencio, Lun Yu, Imane Chaib, Chaoqun You, Bartomeu Massutí, Yue Song, A. Vergnenègre, Huan Lu, Guillermo López-Vivanco, Weixin Hu, G. Robinet, Jun Yan, Amelia Insa, Xiaoyue Xu, Margarita Majem, X. Chen, R. de las Peñas, Niki Karachaliou, María Ángeles Sala, Qingpo Wu, Dolores Isla, Yanping Zhou, Nathalie Baize, F. Zhang, J. Garde, Paul Germonpré, Stefan Rauh, Hamed Alhusaini, M. Sánchez-Ronco, Ana Drozdowskyj, José Javier Sánchez, Carlos Camps, B. Liu, Rafael Rosell, Benoît Colinet, Jacques De Grève, Paul Germonpré, H. Chen, X. Chen, Juan Du, Yanan Gao, Jing Hu, Weixin Hu, W. Kong, Lu Li, R. Li, X. Li, B. Liu, Jingyu Liu, Huan Lu, Xiaoping Qian, Weihong Ren, Yue Song, Lei Wang, Jia Wei, Wen Li, Qingpo Wu, Xiangwei Xiao, Xiaoyue Xu, Jun Yan, Jianning Yang, Mu‐Zi Yang, Yanqing Yang, Jian Yin, Chaoqun You, Lun Yu, Xiu hui Yue, F. Zhang, Jiliang Zhang, Yanping Zhou, Liang Zhu, Zhengyun Zou, Nathalie Baize, P. Bombaron, C. Chouaïd, Éric Dansin, P. Fournel, G. Fraboulet, R. Gervais, S. Hominal, S. Kahlout, H. Lecaer, H. Léna, J. Letreut, C. Locher, O. Molinier, Isabelle Monnet, G. Oliviéro, G. Robinet, Reineke A. Schoot, P. Thomas, A. Vergnenègre, Guy Berchem, Stefan Rauh, Hamed Al Husaini, Francisco Aparisi, Edurne Arriola, Iván Ballesteros, I. Barneto, R. Bernabé, Ana Blasco, Joaquím Bosch-Barrera, Isabel Bover, Virginia Calvo, Carlos Camps, Enric Carcereny, S. Catot, Manuel Cobo, R. de las Peñas, Manuel Dómine, Enriqueta Felip, M.R. García-Campelo, Carlos García Girón, Ronald G. García, Raquel García Sevila, J. Garde, Amaya Gascó, J. Gil, J.L. González-Larriba, Susana Hernando-Polo, Eloísa Jantus‐Lewintre, Amelia Insa, Dolores Isla, Begoña Jiménez, P. Lianes, Rafael López‐López, Ana López Martín, Guillermo López-Vivanco, José A. Macías, Margarita Majem, Juan Luis Martí-Ciriquián, Bartomeu Massutí, R. Montoyo, Daniela Morales-Espinosa, Teresa Morán, María Ángeles Gálvez Moreno, Cinta Pallarés, Marta Parera, R. Pérez-Carrión, R. Porta, Mariano Provencio, N. Reguart, Rafael Rosell, Francisco Molina Rosillo, María Ángeles Sala, J. M. Sanchez, Ivana Sullivan, J. Terrasa, José Trigo, Javier Valdivia, N. Viñolas, Santiago Viteri, M. Botia-Castillo, José Luís Mate, M. Perez-Cano, José Luis Ramírez, B. Sanchez-Rodriguez, Miquel Tarón, M. Tierno-Garcia, Erika Mijangos, Juan Ocaña, E. Pereira, Jingjing Shao, Xiaoting Sun, R. O'Brate,

BRCA gene mutations in cancer

In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients.Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS).Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82).Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches.NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.