Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours

Abstract

Background: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9–16.7): 13.2 (7.4–16.8) and 13.0 (9.2–20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7–33.8) in the total population: 21.3% (11.9–33.7) in treatment-naive and 28.9% (16.4–44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0–not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

Real-world use of sunitinib in Japanese patients with pancreatic neuroendocrine tumors: results from a post-marketing surveillance study

“…The results of this PMS study showed the safety profile of sunitinib in Japanese patients with pNETs treated in clinical practice was similar to the safety profile in patients treated in clinical trials, including the global phase III and IV trials and the phase II trial in Japanese patients [ 8 , 11 , 19 ]. Furthermore, there were no new safety concerns in sunitinib-treated Japanese patients with pNETs, and the commonly reported AEs were similar to those previously reported in clinical trials and surveillance studies of sunitinib in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors [ 20 – 24 ].…”

“…In fact, the median duration of treatment in this PMS study was shorter than in the global phase IV trial (356 days) or the real-world clinical setting of the Japanese clinical study (490 days) [ 19 , 25 ]. The longer treatment duration in those trials likely led to the better outcomes: ORR was 24.5% in the global phase IV trial and 44% in the Japanese study [ 19 , 25 ]. Keeping patients on treatment longer, by appropriately managing AEs at early stages, is essential for achieving better clinical outcome in sunitinib-treated patients with pNETs.…”

“…The most common AEs of bone marrow depression observed in this Japanese PMS study were lower than those reported in the global phase IV study and included neutrophil count decreased (neutropenia in the global phase IV) (27.4% vs. 53.8%) and white blood cell count decreased (leukopenia in the global phase IV) (19.4% vs. 43.4%), respectively [ 19 ]. One potential reason for the lower frequency of these AEs in this Japanese PMS study compared with the global phase IV trial is the shorter treatment duration (165 vs. 490 days, respectively) [ 19 ].…”

Sunitinib in pancreatic neuroendocrine tumors. Clinical case

“…В 2018 г. Raymond и соавт. [6,7] подтвердили результаты 3 фазы в исследовании 4 фазы у пациентов с прогрессирующими неоперабельными НЭО ПЖ G1-2. Медиана ВБП у пациентов, получавших сунитиниб в дозе 37,5 мг в день ежедневно, составила 13,2 месяца, а частота объективных ответов -24,5%.…”

Potential for use sunitinib in pancreatic neuroendocrine tumors

“…В дальнейшем Raymond и соавт. [6,7] провели исследование 4-й фазы (NCT01525550) при прогрессирующих, высокодифференцированных, неоперабельных или диссеминированных НЭО ПЖ. Пациенты также получали сунитиниб в дозе 37,5 мг в день ежедневно.…”