Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen.
First-line triplet chemotherapy plus bevacizumab (FIr-B/FOx) can improve efficacy of metastatic colorectal cancer (MCRC), KRAS wild-type and mutant. Prognostic relevance of KRAS genotype was evaluated in patients unfit for FIr-B/FOx, treated with conventional medical treatments. Consecutive MCRC patients not eligible for FIr-B/FOx regimen due to age (≥75 years) and/or comorbidities were treated with tailored conventional first-line treatments. KRAS codon 12/13 mutations were screened by direct sequencing. Activity and efficacy were evaluated and compared according to medical treatments, age (non-elderly and elderly≥65 years), comorbidity stage (Cumulative Illness Rating Scale), metastatic extension (liver-limited and other/multiple metastatic), and KRAS genotype, using log-rank. Selected first line treatments were medical in 37 patients (92.5%), and surgical in 3 patients (7.5%). Medical treatment regimens: triplet, 18 (45%); doublet, 15 (37.5%); mono-therapy, 4 (10%). At median follow-up of 8 months, objective response rate (ORR) was 37%, median progression-free survival (PFS) 7 months, liver metastasectomies 8% (liver-limited disease 37.5%), median overall survival (OS) 13 months. Triplet regimens failed to significantly affect clinical outcome, compared to doublet. According to KRAS genotype, ORR, PFS and OS were, respectively: wild-type 50%, 8 months, 13 months; mutant 25%, 6 months, 9 months. KRAS genotype wild-type compared to mutant significantly affected PFS, while not OS. KRAS c.35 G>A mutation (G12D) significantly affected worse PFS and OS compared to wild-type and/or other mutations. KRAS genotype, specifically the c.35 G>A KRAS mutation, may indicate poor prognosis in MCRC patients unfit for intensive medical treatments.
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy.
Gemma
G
Bruera
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy.
Katia
K
Cannita
Radiology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy.
Aldo Victor
AV
Giordano
Hepatobiliar-Pancreatic Surgery, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy.
Roberto
R
Vicentini
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy.
Corrado
C
Ficorella
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, I-67100 L'Aquila, Italy.
Enrico
E
Ricevuto
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins