Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status.
BACKGROUND
Scarce data are available about safety and efficacy of cetuximab in elderly metastatic colorectal cancer (mCRC) patients.


METHODS
We retrospectively analysed 54 irinotecan-refractory mCRC patients aged≥70 years treated with cetuximab plus irinotecan and evaluated clinical outcome according to KRAS and BRAF mutational status.


RESULTS
Median age was 73 years (70-82). Main grade 3-4 toxicities were skin rash (15%), diarrhea (19%) and neutropenia (13%). Irinotecan dose reduction was necessary in 39% of patients. Fifty-two (96%) patients were analysed for KRAS and BRAF status. The 29 KRAS wild-type patients achieved better RR (31% vs 4%; p=0.030) and median PFS (4.21 months vs 3.95 months; p=0.034; HR: 0.50, 95% CI: 0.27-0.95) when compared with KRAS mutated ones. RR (41% vs 3%; p=0.001) and mPFS (4.57 months vs 3.78 months, p=0.001; HR: 0.35, 95% CI: 0.19-0.66) were significantly higher among the 22 KRAS and BRAF wild-type patients compared to the 30 KRAS or BRAF mutated ones.


CONCLUSIONS
Cetuximab plus irinotecan has a favourable safety profile in elderly mCRC patients, but a reduced dose of irinotecan should be considered. Such a combination can be a useful option for elderly KRAS and BRAF wild-type patients.
Fornaro
Lorenzo
L
U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Baldi
Giacomo Giulio
GG
Masi
Gianluca
G
Allegrini
Giacomo
G
Loupakis
Fotios
F
Vasile
Enrico
E
Cupini
Samanta
S
Stasi
Irene
I
Salvatore
Lisa
L
Cremolini
Chiara
C
Vincenzi
Bruno
B
Santini
Daniele
D
Tonini
Giuseppe
G
Graziano
Francesco
F
Ruzzo
Annamaria
A
Canestrari
Emanuele
E
Magnani
Mauro
M
Falcone
Alfredo
A
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D017211:Treatment Failure; D018631:ras Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin