Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies(aEuro)
Por:
Moran, T, Wei, J, Cobo, M, Qian, X, Domine, M, Zou, Z, Bover, I, Wang, L, Provencio, M, Yu, L, Chaib, I, You, C, Massuti, B, Song, Y, Vergnenegre, A, Lu, H, Lopez-Vivanco, G, Hu, W, Robinet, G, Yan, J, Insa, A, Xu, X, Majem, M, Chen, X, de las Penas, R, Karachaliou, N, Sala, MA, Wu, Q, Isla, D, Zhou, Y, Baize, N, Zhang, F, Garde, J, Germonpre, P, Rauh, S, ALHusaini, H, Sanchez-Ronco, M, Drozdowskyj, A, Sanchez, JJ, Camps, C, Liu, B, Rosell, R
Publicada:
1 nov 2014
Resumen:
We conducted two nonindustry biomarker-directed randomized clinical trials in advanced non-small-cell lung cancer, comparing nonselected cisplatin-based chemotherapy with therapy customized by BRCA1 and RAP80 levels: a European phase III trial and an analogous Chinese phase II trial. These trials have laid the groundwork for future research to define predictive models for chemotherapy outcome.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.
Filiaciones:
Moran, T:
Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Med Oncol Serv, Badalona 08916, Spain
Wei, J:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Cobo, M:
Hosp Carlos Haya, Med Oncol Serv, Malaga, Spain
Qian, X:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Domine, M:
Fdn Jimenez Diaz, Med Oncol Serv, E-28040 Madrid, Spain
Zou, Z:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Bover, I:
Hosp Son Llatzer, Med Oncol Serv, Palma De Mallorca, Spain
Wang, L:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Provencio, M:
Hosp Puerta de Hierro, Med Oncol Serv, Madrid, Spain
Yu, L:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Chaib, I:
Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Med Oncol Serv, Badalona 08916, Spain
You, C:
Suqian Gen Hosp, Dept Oncol, Suqian, Peoples R China
Massuti, B:
Hosp Gen Alicante, Med Oncol Serv, Alicante, Spain
Song, Y:
Jinling Hosp, Dept Pneumol, Nanjing, Jiangsu, Peoples R China
Vergnenegre, A:
CHU Limoges, Serv Pathol Resp & Allergol, Limoges, France
Lu, H:
Taizhou Gen Hosp, Dept Pneumol, Taizhou, Peoples R China
Lopez-Vivanco, G:
Hosp Cruces, Med Oncol Serv, Bilbao, Spain
Hu, W:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Robinet, G:
CHU Brest, Serv Pneumol, F-29285 Brest, France
Yan, J:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Insa, A:
Hosp Clin Valencia, Med Oncol Serv, Valencia, Spain
Xu, X:
Northern Jiangsu Peoples Hosp, Dept Pneumol, Yangzhou, Peoples R China
Majem, M:
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain
Chen, X:
Huaian Gen Hosp, Dept Oncol, Huaian, Peoples R China
de las Penas, R:
Hosp Prov Castellon, Med Oncol Serv, Castellon de La Plana, Spain
Karachaliou, N:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst, Translat Res Unit, Barcelona, Spain
Sala, MA:
Hosp Basurto, Med Oncol Serv, Bilbao, Spain
Wu, Q:
Yixin Gen Hosp, Dept Oncol, Yixin, Peoples R China
Isla, D:
Hosp Lozano Blesa, Med Oncol Serv, Zaragoza, Spain
Zhou, Y:
Yixin Gen Hosp, Dept Oncol, Yixin, Peoples R China
Baize, N:
CHU Angers, Dept Pneumol, Angers, France
Zhang, F:
Maanshan Gen Hosp, Dept Oncol, Maanshan, Peoples R China
Garde, J:
Hosp Arnau Vilanova, Med Oncol Serv, Valencia, Spain
Germonpre, P:
Univ Antwerp Hosp, Dept Pulm Med, Edegem, Belgium
Rauh, S:
Ctr Hosp Emile Mayrisch, Dept Internal Med & Oncol, Luxembourg, Luxembourg
ALHusaini, H:
King Faisal Canc Ctr, Ctr Oncol, Riyadh, Saudi Arabia
Sanchez-Ronco, M:
Univ Alcala De Henares, Dept Hlth & Medicosocial Sci, Madrid, Spain
Drozdowskyj, A:
PIVOTAL SL, DMBS, Madrid, Spain
Sanchez, JJ:
Autonomous Univ Madrid, Dept Prevent Med, E-28049 Madrid, Spain
Camps, C:
Hosp Gen Valencia, Med Oncol Serv, Valencia, Spain
Liu, B:
Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Jiangsu, Peoples R China
Rosell, R:
Hosp Badalona Germans Trias & Pujol, Canc Biol & Precis Med Program, Catalan Inst Oncol, Badalona 08916, Spain
MORe Fdn, Barcelona, Spain
Canc Therapeut Innovat Grp, New York, NY USA
Bronze
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