TY - JOUR
T1 - Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM)
T2 - A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX
AU - Ciardiello, F.
AU - Normanno, Nicola
AU - Martinelli, Erika
AU - Troiani, Teresa
AU - Pisconti, Salvatore
AU - Cardone, Claudia
AU - Nappi, Anna
AU - Bordonaro, A. R.
AU - Rachiglio, Anna Maria
AU - Lambiase, Matilde
AU - Latiano, Tiziana Pia
AU - Modoni, G.
AU - Cordio, Stefano
AU - Giuliani, Francesco
AU - Biglietto, M.
AU - Montesarchio, V.
AU - Barone, Carlo
AU - Tonini, Giuseppe
AU - Cinieri, Saverio
AU - Febbraro, Antonio
AU - Rizzi, D.
AU - Vita, F. De
AU - Orditura, M.
AU - Colucci, G.
AU - Maiello, Evaristo
AU - Iaffaioli, Rosario Vincenzo
AU - Nasti, Guglielmo
AU - Botti, Gerardo
AU - Tatangelo, Fabiana
AU - Chicchinelli, Nicoletta
AU - Montrone, Mirko
AU - Sebastio, A.
AU - Guarino, Tiziana
AU - Simone, Giovanni
AU - Graziano, Paolo
AU - Chiarazzo, Cinzia
AU - Maggio, Gabriele Di
AU - Longhitano, Laura
AU - Manusia, Mario
AU - Cartenì, Giacomo
AU - Nappi, Oscar
AU - Micheli, Pietro
AU - Leo, Luigi
AU - Rossi, Sabrina
AU - Cassano, Alessandra
AU - Tommaselli, E.
AU - Giordano, Guido
AU - Sponziello, Francesco
AU - Marino, Antonella
AU - Rinaldi, Antonio
AU - Romito, Sante
AU - Muda, Andrea Onetti
AU - Lorusso, Vito
AU - Leo, Silvana
AU - Barni, Sandro
AU - Grimaldi, Giuseppe
AU - Aieta, Michele
PY - 2016/6/18
Y1 - 2016/6/18
N2 - Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
AB - Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
KW - Cetuximab
KW - Colorectal cancer
KW - FOLFOX
KW - NGS
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U2 - 10.1093/annonc/mdw136
DO - 10.1093/annonc/mdw136
M3 - Article
VL - 27
SP - 1055
EP - 1061
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 6
M1 - mdw136
ER -