Real-World Clinical Practice of Intensified Chemotherapies for Metastatic Pancreatic Cancer: Results from a Pan-European Questionnaire Study

Abstract

Introduction: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe. Methods: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer. Results: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer. Conclusion: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.

First-line and second-line treatment of patients with metastatic pancreatic adenocarcinoma in routine clinical practice across Europe: a retrospective, observational chart review study

“…In contrast to our study, a web-based physician questionnaire study of first-line treatment trends in 19 European countries in 2015 found that gemcitabine+nab-paclitaxel was used more frequently than FOLFIRINOX 21. It should be noted that this study reported more data from Germany, Italy and Spain than from France and the UK, both of which represent a total of 120 million inhabitants and were less likely to use gemcitabine+nab-paclitaxel in the current study.…”

“…As anticipated, first-line choices influenced second-line treatment in the current study, with the most commonly used therapies in the second-line setting being gemcitabine monotherapy following FOLFIRINOX, and 5-FU-based therapies other than FOLFIRINOX following gemcitabine+nab-paclitaxel. Similar second-line treatment trends were observed in our study and the study by Le and colleagues 21. It is interesting to note that over a quarter of patients did not continue past first-line treatment; this may reflect the shortage of approved later-line regimens for patients with pancreatic adenocarcinoma.…”

“…Patient characteristics, comorbidities and safety profile affect treatment choices, which may also vary depending on country, treatment guidelines, treatment goals, physician preference and reimbursement status 21. Published data regarding the European mPAC treatment landscape are very limited.…”

Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting

“…A recent US-based study that included academic, private, and community-based oncology practices reported similar rates of utilization, with 38, 29, and 16% use of nab-paclitaxel plus gemcitabine, FOLFIRINOX, and gemcitabine monotherapy as 1L therapy in 2015, respectively [9]. Similarly, a questionnaire study of physicians in 19 European countries reported high utilization of nab-paclitaxel plus gemcitabine (47%) and FOLFIRINOX (42%), when using intensified regimens as 1L therapy for metastatic pancreatic cancer [10]. …”

“…In the real-world study by Wang et al, a significantly higher proportion of patients required dose modifications with FOLFIRINOX (40%) compared with nab-paclitaxel plus gemcitabine (14%) and gemcitabine monotherapy (9%; p  < 0.001) [13]. The European questionnaire study reported a higher likelihood of protocol deviation with FOLFIRINOX than nab-paclitaxel plus gemcitabine ( p  < 0.01) [10]. …”