Efficacy of anti-VEGF & anti-EGFRs in microsatellite instable (MSI-H) metastatic colorectal cancer, Turkish Oncology Group (TOG) study.

Abstract

e15507 Background: Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) CRC tumors constitute of 5% of mCRC. Immunotherapy is a new standard, but it is difficult to give it all. 5FU based treatment with antiEGFRs in RAS/BRAF-wt or bevacizumab (B) is used in mCRC. Data is limited for the efficacy of B or antiEGFRs in dMMR/MSI-H mCRC due to small number of cases in CRC population in trials. Aims : Evaluation of prognostic factors & 1 st line 5FU based treatment with B/antiEGFRs efficacy in mCRC. Methods: dMMR/MSI-H mCRC patients (pts) with 1 st line B/antiEGFRs were evaluated retrospectively. Results: 132 patients were included. Mutation rates were as 35.6% (n:47) for RAS, 12.1% (n:16) for BRAF.Median PFS was 10.9 (95%CI: 9.2-12.6) months. Median OS was 44 months (95% CI 26.23-63.03). 82 (62.1%) pts had primary tumor resection (PTR), 26 (19.7%) had PTR & metastasectomy. 17 (12.8%) de novo mCRC pts had maximal cytoreductive surgery (MCS). 14 (10.6%) pts had subsequent IO. In multivariate analysis, RAS/BRAF mutation status, MCS & subsequent IO are defined as prognostic factors for OS (p<0.01, p: 0.022, p: 0.005, respectively). No statistically significant survival (PFS, OS) difference was detected. Conclusions: dMMR/MSI-H mCRC is an entity with different tumor biology. We consider that dMMR/MSI-H mCRC pts with BRAF wt, MCS & subsequent IO have better outcomes with 1st line 5FU based treatment with B/antiEGFRs. Baseline characteristics & survival analysis. n(%) PFS(months) OS (months) Univariate analysis Univariate analysis Multivariate analysis %95 CI P value %95 CI P value %95 CI HR P value Age (year) 60(23-82) 0.86 0.62 <60 50 8.4-11.3 25.0-64.7 ≥60 72 9.8-15.1 17.4-71.8 Sex 0.55 Female 56(43.2) 7.5-14.7 6.7-58.5 0.59 Male 67(50.8) 7.5-12.4 26.9-62.3 Primary Tumor Location 0.045 0.036 Right 81(61.4) 7.9-10.7 24.7-85.6 Left 33(25) 9.1-15.8 16.0-73.7 Rectum 18(13.6) 9.2-12.6 15.9-44.0 De novo Metastasis 0.55 0.04 Yes 72(54.5) 9.2-12.6 21.1-68.1 No (recurrent) 60(45.5) 61.1-14.4 11.8-53.9 Mutation status 0.037 <0.01 2.72-20.05 7.9 <0.01 KRAS/NRAS mutant 47(35.6) 6.5-16.4 20.4-69.3 BRAF mutant 16(12.1) 5.7-12.0 0.0-23.5 RAS/BRAF Wild 69(52.2) 9.3-12.4 21.7-43.0 Site of Metastasis 0.092 0.053 Liver 62(46.9) 8.4-13.8 24.6-77.1 Peritoneum 30(22.7) 8.5-10.1 32.5-59.4 Others* 24(18.1) 2.5-20.1 18.5-44.5 Biological Treatment 0.089 No 34(25.7) 4.6-11.3 Bevacizumab 72(54.5) 9.7-17.1 Cetuximab 20(15.1) 10.2-14.7 Panitumumab 6(4.5) 2.7-19.9 Maintenance treatment 0.007 0.14 0.20-1.07 0.46 0.72 Yes 37(28) 12.4-15.5 29.9-80.4 No 95(71.9) 7.1-10.3 8.9-54.2 Maximal cytoreductive surgery 0.89 0.030 0.15-0.86 0.36 0.022 Yes 17(12.8) 6.8-11.0 15.0-50.2 No 115(87.1) 9.3-13.0 17.9-92.4 İmmunotherapy in Subsequent Treatment 0.005 0.28-0.51 0.12 0.005 Yes 14(10.6) No 118(89.4) 20.2-42.8 *Others: Lung, bone, brain, nonregional lap.