Introduction:Capecitabine and temozolomide(CAPTEM) has significant activity in patients(pts) with metastatic low grade pancreatic neuroendocrine tumors(NETs). However, there is limited data regarding the activity of CAPTEM in pts with metastatic well-differentiated intermediate and high grade pancreatic and non-pancreatic NETs. The objective of this study was to assess the functional imaging response, survival and tolerability of CAPTEM in this population.
Methods:A retrospective audit of pts with metastatic well-differentiated intermediate(WHO grade 2) or high(WHO grade 3) NETs at Peter MacCallum Cancer Centre. Pts received capecitabine 750 mg/m2 orally bd days 1–14 and temozolomide 100 mg/m2 bd days 10–14 of a 28-day cycle between March 2013- March 2017. Data regarding functional imaging response, progression free and overall survival, and toxicities was collected.
Results:Thirty two pts received CAPTEM[grade 2(n=21, 66%), grade 3(n=11, 34%), Ki67 <55%(n= 7, 21.9%), Ki67 >55%(n= 4, 12.5%). Primary site were gastroenteropancreatic(GEP) in 53%, lung 37.5% and unknown 9.4%. Liver(72%) was the most common site of metastasis followed by bony and nodal disease in 62% each. CAPTEM was first line therapy in 22%. Prior PRRT was in 22%. Median number of cycles received was 6. Best PET response was complete metabolic response in 12.5%,partial metabolic response in 34.4% and stable disease in 15.6%. With 31 months of median follow up, the two-year overall survival(OS) was 42%, with a median OS of 24 months. There was a trend towards improved median progression free survival (PFS) in pts with low grade 3 (Ki67<55%) versus high grade 3 (Ki67 >55%) NETs(15 vs 4 months, p= 0.11). Ten (31.3%) pts experienced a grade 3 or 4 toxicity, with nausea (15.6%), thrombocytopaenia (12.5%), and fatigue (9.4%) the most common toxicities reported.
Conclusion:The encouraging results of CAPTEM in a subgroup of grade 3 (Ki 67 < 55) metastatic NET needs to be further evaluated in a randomized trial.