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Poster display session

5346 - Prevalence of KRAS/NRAS/BRAF mutations detected by massive parallel sequencing and differential outcomes in MCRC patients (pts) treated with first line FIr-B/FOx adding bevacizumab (BEV) to triplet chemotherapy.

Date

09 Sep 2017

Session

Poster display session

Presenters

Gemma Bruera

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

G. Bruera1, F. Pepe2, U. Malapelle2, P. Pisapia2, A. Dal Mas3, G. Calvisi3, G. Troncone2, E. Ricevuto1

Author affiliations

  • 1 Oncology Territorial Care; Department Of Biotechnological And Applied Clinical Sciences, Oncology Network ASL1 Abruzzo, S. Salvatore Hospital, ASL1 Abruzzo; University of L'Aquila, 67100 - L'Aquila/IT
  • 2 Department Of Public Health,, University Federico II, Napoli/IT
  • 3 Pathology, S. Salvatore Hospital, ASL1 Abruzzo, L'Aquila/IT
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Resources

Abstract 5346

Background

KRAS/NRAS/BRAF genotypes guide tailoring of first and subsequent lines of MCRC treatment strategy. First line triplet chemotherapy/BEV regimens significantly improved progression-free survival (PFS) and overall survival (OS) in MCRC patients. OS may be significantly worse in KRAS c.35 G > A and BRAF mutant (mut) MCRC. Prevalence and differential clinical outcome according to KRAS/NRAS/BRAF genotype was evaluated in MCRC patients treated with FIr-B/FOx intensive regimen.

Methods

Tumoral samples of 67 MCRC pts treated with FIr-B/FOx (77% overall) were analyzed through a 50 genes panel (PGM/Colon Lung Cancer) by ION Torrent. KRAS exons 2-4 (KRAS2-4), NRAS exons 2-4 (NRAS2-4), and BRAF exon 15 (BRAF15) were evaluated. Molecular diagnostic criteria for mutation detection: >500×sequence coverage; >1% mutant allelic fraction. Clinical outcomes (PFS and OS) were evaluated and compared by log-rank.

Results

KRAS2-4 mut were 42 (66.7%), 4 not evaluable; NRAS2-4mut 13 (19.4%); BRAF15 mut 5 (7.5%). KRAS2-4/NRAS2-4/BRAF15 mut MCRC patients were 49 (77.8%), wt 14 (22.2%): single gene mut 40 (63.5%), KRAS2-434 (54%), and NRAS2-4 6 (9.5%); >1 mut genes 9 (14.3%), double mut 5 and triple mut 4, specifically double KRAS 1, KRAS/NRAS 2, KRAS/BRAF 1, NRAS/BRAF 1, double KRAS/NRAS 1, KRAS/NRAS/BRAF 3. BRAF15 mut were all atypical and concomitant with KRAS and/or NRAS mutations. Prevalence of KRAS2-4, NRAS2-4, BRAF15 >1 mut samples were 19%, 53.8%, and 100% of each mut gene. At median follow-up 21 months (m), PFS and OS overall, and of KRAS2 genotype were consistent with previously reported; in c.35 G > A KRAS2 mut trendly worse PFS 8 m and OS 14m. Differential clinical outcome of MCRC patients wt and mut were not significantly different: KRAS2-4, PFS 13 and 12m, OS 27m equivalently; NRAS2-4, PFS 16 and 12m, OS 28 and 22m; BRAF15 PFS 14 and 8 m, OS 28 and 11 m; KRAS2-4/NRAS2-4/BRAF15 PFS 18 and 12m, OS 28 and 22m.

Conclusions

Clinical outcome of MCRC patients treated with FIr-B/FOx is not significantly affected by KRAS2-4/NRAS2-4/BRAF15 genotype; efficacy may be increased in triple wt patients; the prevalent c.35 G > A KRAS2 and BRAF15 mut may show worse prognosis.

Clinical trial identification

Legal entity responsible for the study

Enrico Ricevuto

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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