First-line therapies for advanced pancreatic cancer: A perspective based on pharmacological costs

Abstract

Introduction: The introduction of active new agents for the treatment of advanced pancreatic cancer 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) and overall survival (OS). Methods: The present evaluation was restricted to phase III randomized controlled trials (RCTs) in first-line therapy for advanced pancreatic cancer. We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Then, we calculated the pharmacological costs necessary to get the benefit in PFS, for each trial, referring to the median number of cycles reported in each phase III RCT. 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 (e). Results: Our study evaluated 11 phase III RCTs (including 4572 patients). The primary objective of the evaluated studies was OS in all 11 RCTs. OS and PFS range from 5.4 and 2.2 months of gemcitabine alone to 11.1 and 6.4 months of FOLFIRINOX, respectively. The main difference in gain of OS was for FOLFIRINOX, with 4.3 months against gemcitabine alone. The ESMO-MCBS has reached a grade 2 of magnitude of clinical benefit for GEMOX in the Louvet et al. Trial, a grade 3 for the combination of gemcitabine plus nab-paclitaxel in the Von Hoff et al. Trial and a grade 4 for FOLFIRINOX in the Conroy et al. Trial. All other phase III RCTs have reached a grade 1 of magnitude of clinical benefit (from the low grade 1 to the high grade 5). Combining the difference in PFS for the different arms of the phase III RCTs with the highest ESMO-MCBS scores with the pharmacological costs necessary to get the benefit in PFS for each trial, we have obtained 74.12 eper month of PFS gained for FOLFIRINOX, 90.14 per month of PFS gained for GEMOX and 4708.70 eper month of PFS gained for the combination of gemcitabine plus nab-paclitaxel against gemcitabine alone. Conclusion: In recent years new combination chemotherapies, such as FOLFIRINOX and gemcitabine plus nab-paclitaxel, have been added in first-line for advanced pancreatic cancer, based on results of phase III RCTs. It remains to understand how justified are both an increase in costs that an increase in toxicities compared to a minimum of survival gain for a disease with a so poor prognosis (median OS less than 12 months). From this perspective, we believe that "old combination chemotherapies" (e.g. GEMOX) should not be completely abandoned, but reasoned on the individual patient, based on different factors (age, ECOG PS, comorbidity, disease burden) in order to achieve a real tailored therapy.