Quality-of-life in patients with metastatic colorectal cancer (mCRC) treated with aflibercept and FOLFIRI: Interim results of the non-interventional AIO study QoLiTrap

Abstract

Introduction: The anti-angiogenic fusion protein aflibercept targets VEGF-A, VEGF-B and PlGF. Aflibercept is approved in combination with FOLFIRI for treatment of mCRC that is resistant or has progressed after oxaliplatin-containing therapy. Methods: QoLiTrap (AIO-LQ-0113) is a multinational (D, A, CH) ongoing noninterventional study with a recruitment target of 1500 patients. Primary goal is to evaluate Quality-of-life (QoL) in mCRC patients treated with aflibercept+FOLFIRI using the EORTC-QLQ C30 questionnaire at baseline and before every cycle. Results: This interim analysis (data cut-off: 05 December 2017) includes 702 patients (mean age: 64.869.9 years; 65.0% male, 50.9% with documented RAS mutation, ECOG 0-1: 86.0) who completed the baseline and at least 2 post-baseline EORTCQLQC30 questionnaires. Aflibercept was administered for 7 cycles in median (range: 1-65). Median global health score at baseline was 58.3 and decreased moderately (mean change -4.4, p<0.0001) within the first 18 weeks of therapy with no significant worsening in gastrointestinal, dyspnea, and sleep disturbance symptom scales. Reduction was greater in patients with RAS mutation compared to RAS wild-type. 91.9% of patients received prior palliative therapy or prior therapy during metastatic stage. Mainly, study treatment was given as 2nd line treatment, followed by 3rd and 4th line treatment. 64.3% of these patients were pretreated with bevacizumab and 13.7% with anti-EGFR (cetuximab or panitumumab) alone or in combination with chemotherapy. Previous 1st line therapy was primarily oxaliplatin-containing regime with bevacizumab for RAS mutant and with anti EGFR for RAS wildtype. As prior 2nd line therapy bevacizumab was given nearly equally in combination with oxaliplatin or irinotecan for RAS mutant and wildtype; anti-EGFR was combined approximately equal with irinotecan or oxaliplatin for RAS wildtype, too. Evaluable patients pretreated with anti-EGFR and/or bevacizumab receiving study therapy as 2nd line treatment had 13.8% documented CR + PR and 31.5% SD as best response to aflibercept. Sidedness of CRC and RAS mutation status had an impact on best response in these patients. Median PFS of patients pretreated with biologics was 8.3 months (95% CI 7.0- 9.3) and 7.8 months (95% CI 6.4-10.6) for study treatment as 2nd line and 3rd line, respectively. Patients treated with prior anti-EFGR or bevacizumab independent of therapy line had a median PFS of 9.4 months (95% CI 5.9-.) and 7.3 months (95% CI 6.0 - 8.3), respectively; pretreatment with both substance groups yielded a median PFS of 5.7 months (95% CI 5.0 - 8.1). These results corresponded to ORR of 14.6%, 11.0% and 6.3% for patients pretreated with anti-EFGR, bevacizumab or both. No statistically significant differences for median PFS were observed for patients with RAS wildtype or RAS mutation. Toxicity was in line with the known safety profile of the study medications. Conclusion: The current interim analysis showed encouraging effectiveness results for mCRC patients treated with aflibercept+FOLFIRI under routine conditions even for patients with prior anti-EGFR antibody and/or bevacizumab therapy. Best efficacy results were obtained for patients with study treatment as 2nd line. Global health status declined moderately without clinical relevance during study treatment. This study is supported by Sanofi-Aventis Deutschland GmbH.