Vol.:(0123456789) Targeted Oncology https://doi.org/10.1007/s11523-020-00705-1 ORIGINAL RESEARCH ARTICLE Sequential Treatment with Bevacizumab and Afibercept for Metastatic Colorectal Cancer in Real‑World Clinical Practice Tomas Buchler 1  · Igor Kiss 2  · Jana Hornova 1  · Ondrej Fiala 3,4  · Marketa Wiesnerova 5  · Michal Svoboda 5  · Jiri Silar 5  · Katerina Kopeckova 6  · Alexandr Poprach 2  · Jindrich Finek 3  · Lubos Petruzelka 7  · Bohuslav Melichar 8 © Springer Nature Switzerland AG 2020 Abstract Background Bevacizumab and afibercept are currently the mainstay of antiangiogenic therapy for metastatic colorectal carcinoma (mCRC). They are often used in sequence with frst- and second-line chemotherapy, especially in patients with RAS-mutated tumours. Objective The aim of the present study was to investigate the outcomes of patients with mCRC treated with the bevacizumab- afibercept sequence in real-world clinical practice. Patients and Methods Data from a national clinical registry of targeted therapies for mCRC were analysed retrospectively. Overall, there were 366 patients with valid data who received frst-line treatment with bevacizumab and chemotherapy fol- lowed by afibercept with chemotherapy. The majority of the patients (n = 296, 80.8%) had RAS mutated tumours. Results Median cumulative progression-free survival (PFS) from the start of the bevacizumab-containing regimen to progres- sion on afibercept was 18.2 months (95% CI 16.8–19.5). Median PFS for bevacizumab and afibercept was 10.6 months (95% CI 9.5–11.7) and 5.6 months (95% CI 5.1–6.1), respectively. Longer PFS on afibercept was associated with metachronous metastatic disease and longer PFS on bevacizumab. Median overall survival (OS) from the start of frst-line bevacizumab was 32.0 months (95% CI 26.6–37.5). The presence of metastatic disease at diagnosis was associated with worse OS. Conclusions Patients treated with afibercept in real-world clinical practice achieved similar survival outcomes as those treated within randomised trials. Cumulative survival data provide a benchmark for future studies and enable indirect com- parisons with other treatment sequences used in mCRC. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11523-020-00705-1) contains supplementary material, which is available to authorized users. * Tomas Buchler tomas.buchler@ftn.cz Extended author information available on the last page of the article 1 Introduction Anti-angiogenic targeted therapy is one of the major treat- ment modalities in patients with metastatic colorectal can- cer (mCRC). Vascular endothelial growth factor receptors (VEGFRs) play a key role in tumour angiogenesis. Five ligands are known to bind to the three VEGFR isoforms, including vascular endothelial growth factor (VEGF)-A, -B, -C, -D and placental growth factor (PlGF) [1]. PlGF is an N-glycosylated dimeric protein with 53% amino acid homology to VEGF [2]. Like VEGF, PlGF is involved in several physiological and pathological processes such as wound healing, infammation, tissue ischaemia response and tumour growth [ 3 ]. Preclini- cal studies have shown that simultaneous inhibition of VEGF and PIGF or their respective preferential receptors VEGFR-1 and VEGFR-2 synergistically inhibits tumour growth [4]. Afibercept is a fusion protein comprising regions of human VEGFR-1 and VEGFR-2 conjugated to an IgG1 Fc fragment. It functions as a soluble circulating VEGF trap neutralising VEGF-A, VEGF-B and PlGF [5]. In contrast, bevacizumab, the most commonly used VEGF inhibitor, only binds VEGF-A [6]. Afibercept was approved for second-line therapy of mCRC based on the phase III VELOUR study (Afibercept Versus Placebo in mCRC After Failure of an Oxaliplatin- Based Regimen) that enrolled 1226 patients progressing on or after an oxaliplatin-based regimen. Afibercept or placebo were administered with 5-fluorouracil/leucov- orin/irinotecan (FOLFIRI). The overall survival (OS) was 13.5 months in the afibercept plus FOLFIRI arm compared with 12.1 months with FOLFIRI alone. Afibercept also signifcantly improved the progression-free survival (PFS)