Cost-effectiveness of anti-angiogenic agents in second-line treatment for metastatic colorectal cancer. Integrating the EUROPEAN Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) with the costs of drugs

Abstract

Background: In western Countries, colorectal cancer (CRC) is the second most common cause of death from cancer. In particular, the introduction of active new anti-angiogenic agents for the second-line treatment of metastatic CRC (mCRC) is associated with a relevant increase of costs and it is therefore important to make a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression free survival (PFS). Materials and methods: The analysis was conducted to assess the effect of second-line therapy with anti-angiogenic agents on the PFS and was restricted to pivotal phase III randomized controlled trials (RCTs). We calculated the pharmacological costs necessary to get the benefit in PFS, for each trial. Calculations were based on an “ideal patient” (BSA 1.8 sqm; weight 70 Kg). The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to the above pivotal phase III RCTs. Results: The present analysis evaluated 4 phase III RCTs, including 3938 patients. PFS ranged from 2.7 months of bevacizumab alone in the E3200 trial to 7.3 months of the combination of FOLFOX and bevacizumab in the same trial. ESMO-MCBS reached medium score for VELOUR trial and low grade scores (grade 1 and 2) for RAISE, TML and E3200 trials, respectively. Dividing the costs of therapy by the measure of efficacy represented by PFS we found out that the lowest cost per month of PFS gained (4581 €) was associated with the use of FOLFIRI plus aflibercept; the highest cost per month of PFS gained (23 827 €) was associated with the use of FOLFIRI plus ramucirumab. Conclusions: Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, aflibercept in combination with FOLFIRI is a cost-effective second-line treatment for patients with mCRC. The lack of correlation between PFS and OS is a well known phenomenon with the clinical use of anti-angiogenic treatment and reinforces the importance of the evaluation of PFS as a strong end-point, even on a pharmaco-economic perspective.