Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study

Abstract

Background: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. Methods: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. Results: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. Conclusion: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines

“…There is evidence, however, that this is not the case; OS was very long (median 104 months from diagnosis of mP-NETs and 62% 5-year OS). OS is longer than that in a recent study of 92 patients with unresectable/metastatic P-NET (60-month median OS and 51% 5-year OS) (Berdelou et al 2016). Furthermore, this included a minority of welldifferentiated grade 3 NET (NET-G3), that we chose to include in Group 3.…”

“…This study also provides data for treatments given in mP-NET. As reported by Berdelou et al (2016), we demonstrate that not all patients will benefit from all approved or recommended therapeutic options in mP-NET. In the present study, just over half of deceased patients received three lines or less.…”

“…PD, progressive disease; SD, stable disease. required first-line chemotherapy (Group 3), which was 60% in the study reported by Berdelou et al (2016). This indicates the need for clinical trials to define the best chemotherapy regimen: intravenous or oral agents; streptozotocin/temozolomide-based or oxaliplatin-based chemotherapy; impact of MGMT status on this choice (Dussol et al 2015); association with bevacizumab (Ducreux et al 2014).…”

“…In the present study, just over half of deceased patients received three lines or less. One goal of international research would be to design a prospective multicenter cohort with a very long follow-up to assess the main reasons for this, such as comorbidities, persistent treatment-related toxicity as recently suggested by Berdelou et al (2016) or too rapid disease progressions in some high-grade mP-NET. We also found that surgery of the primary tumor, more often performed for tumor in the tail of the pancreas and for low-grade tumor and low tumor burden, is associated with a better OS.…”

“…We now have data from phase III studies investigating SSA (Caplin et al 2014), everolimus (Yao et al 2011) and sunitinib (Raymond et al 2011) in P-NET, but only in selected populations. Moreover, patients do not receive all efficient treatments in real life (Berdelou et al 2016), and therefore, the choice of the first-line treatment is of crucial importance.…”