P-149 Impact of sequence of biologic therapies on overall survival (OS) in patients with RAS wild-type (WT) metastatic colorectal carcinoma (mCRC): an exploratory, retrospective pooled analysis

Abstract

Introduction: Biologic therapies such as epidermal growth factor receptor inhibitors (EGFRi) and vascular endothelial growth factor inhibitors (VEGFi) improve clinical outcomes of patients with RAS WT mCRC when added to first-line chemotherapy, compared with chemotherapy alone. Preclinical data suggest that the sequence of therapy may be important in terms of tumour biology, but optimal sequencing of targeted therapies has not been determined in a phase III prospective clinical trial. Here we report an exploratory analysis of OS for patients with RAS WT mCRC treated with either first-line panitumumab and second-line VEGFi therapy, or first-line bevacizumab and second-line EGFRi. Methods: An exploratory analysis of OS data from three randomised mCRC studies was conducted: PEAK (NCT00819780), a phase II study of first-line panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6; PRIME (NCT00364013), a phase III trial of first-line panitumumab + FOLFOX4 vs FOLFOX4; and study 181 (NCT00339183), a phase III trial of second-line panitumumab + FOLFIRI vs FOLFIRI. OS was analysed for all RAS WT patients who received first-line panitumumab (PEAK and PRIME) or first-line bevacizumab (PEAK and 181), followed by second-line treatment with VEGFi or EGFRi, respectively. Results: Overall, 104 patients were included: 66 were treated with first-line panitumumab followed by second-line VEGFi and 38 received first-line bevacizumab, followed by second-line EGFRi. At the time of the reported data cut-offs, 63.6% of panitumumab→VEGFi patients and 92.1% of bevacizumab→EGFRi patients had died. HRs for OS with the two treatment sequence comparisons are shown in the table. Overall, pooled analysis resulted in a median OS of 36.8 (95% CI: 30.3-43.8) vs 27.8 (95% CI: 24.2-35.6) months in patients treated with panitumumab→VEGFi vs bevacizumab→EGFRi (HR for OS [95% CI]: 0.65 [0.42-1.03]). Conclusion: Although numbers are small, this exploratory analysis may suggest a trend towards an OS benefit for first-line panitumumab + chemotherapy followed by second-line VEGFi treatment, compared with first-line bevacizumab followed by second-line EGFRi in patients with RAS WT mCRC. A larger, prospective biologics sequencing trial is needed to confirm these findings.