Prospective, observational study evaluating the effectiveness and safety of aflibercept plus FOLFIRI in metastatic colorectal cancer (mCRC) according to Polish reimbursement criteria

Aflibercept plus FOLFIRI was approved in Poland in 2017 for the treatment of mCRC patients aprior oxaliplatin-based regimen, based on results of VELOUR phase III trial (Van Cutsem et al. JCO 2012; 30: 3499-3506 ). This prospective observational studymandated by Polish Health Authorites evaluated the effectiveness and safety of aflibercept plus FOLFIRI according to Polish reimbursement criteria in daily clinical practice.

Consecutive patients with mCRC who progressed during or after an oxaliplatin-containing regimen were prospectively enrolled and treated with aflibercept (4 mg/kg IV) followed by FOLFIRI regimen every 2 weeks until progression or unacceptable toxicity. One prior line of chemotherapy in metastatic stage was allowed. Primary end-point was progression-free survival (PFS). Secondary end-points included overall survival (OS) and safety.

93 patients (males 59.1%, median age 62 years [range 29-81]) were enrolled in 17 Polish oncology sites. The tumor was left-sided in 81.7% of patients; KRAS, NRAS, BRAF mutations were present in 41.9%, 3.2% and 4.3% of patients, respectively; 88.2% of patients underwent a prior resection of the primary tumor, 41.9% had received prior adjuvant chemotherapy and 25.8% had a prior resection of metastases. Overall, patients received a median of 10 cycles (range 1-38) with a median duration of exposure of 5.3 months. Median PFS was 8.4 months [95% CI, 6.9-9.9]; at one year, 27 patients (29%) remained free from progression. Over a median follow-up of 12 months, there were 18 deaths; median OS was of 12.0 months (95% CI, 10.2–13.9) with a survival rate at 12 months of 79%. Outcomes in terms of PFS and OS did not significantly differ according to primary tumor location, metastatic site (liver only, liver and other sites, other sites only) and presence or absence of KRAS mutation. Of 93 patients exposed to aflibercept, 32 (34%) experienced grade ≥3 adverse events (AEs) and 26 (28.0%) discontinued therapy due to AEs. Main grade ≥3 AEs were neutropenia (16%), hypertension (8%), diarrhea (4%) and stomatitis (4%).

Results of this prospective observational study suggests that aflibercept plus FOLFIRI administered in mCRC patients who progressed during or after an oxaliplatin-based regimen retains its activity regardless of tumor sideness, KRAS status and metastatic site, and shows a manageable safety profilein daily clinical practice.

The authors.

Sanofi.

M. Sikora-Skrabaka: Honoraria (self): Quantum Satis. All other authors have declared no conflicts of interest.