PD-027 BRAF mutant and RAS mutant patients treated with FOLFIRI plus Bevacizumab or FOLFIRI plus Cetuximab. Role of ETS and molecular markers in FIRE-3 (AIO KRK-0306)

Introduction: The FIRE-3 study (AIO KRK-0306) was initiated as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. But overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Here we investigated if there are also biomarkers predicting outcome for both the RAS- or BRAF mutated subgroups of FIRE-3.Methods: In this exploratory analysis outcome parameters of both the BRAF- or RAS mutant subgroups were correlated with early tumor shrinkage and expression levels of amphiregulin and epiregulin.Results: See table uploaded as figure/graphLegend: RAS = Rat Sarkoma, BRAF = proto-oncogene B-Raf; FOLFIRI = 5-Flurouracil, Leucovorin, Irinotecan; OS = overall survival; PFS = progression-free survival, p* = Log-rank test p; p**= two sided Fisheŕs exact test p; $ = median test p ETS = early tumor shrinkage; non-ETS = non early tumor shrinkage; HR = Hazard ratio;Conclusion: Patients with RAS- or BRAF-mutated tumors had a markedly better outcome if ETS was reached in the cet-arm, but not in the bev-arm of FIRE-3. These response-related parameters suggest that RAS- and BRAF mutant tumors may represent heterogenic populations Introduction: The FIRE-3 study (AIO KRK-0306) was initiated as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. But overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Here we investigated if there are also biomarkers predicting outcome for both the RAS- or BRAF mutated subgroups of FIRE-3. Methods: In this exploratory analysis outcome parameters of both the BRAF- or RAS mutant subgroups were correlated with early tumor shrinkage and expression levels of amphiregulin and epiregulin. Results: See table uploaded as figure/graph Legend: RAS = Rat Sarkoma, BRAF = proto-oncogene B-Raf; FOLFIRI = 5-Flurouracil, Leucovorin, Irinotecan; OS = overall survival; PFS = progression-free survival, p* = Log-rank test p; p**= two sided Fisheŕs exact test p; $ = median test p ETS = early tumor shrinkage; non-ETS = non early tumor shrinkage; HR = Hazard ratio; Conclusion: Patients with RAS- or BRAF-mutated tumors had a markedly better outcome if ETS was reached in the cet-arm, but not in the bev-arm of FIRE-3. These response-related parameters suggest that RAS- and BRAF mutant tumors may represent heterogenic populations