The purpose of the trial.  Treatment options are sometimes limited in patients with metastatic neuroendocrine neoplasms (NEN). The primary endpoint was response rate (using RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Immune profiling was performed by mass cytometry to evaluate the effect on peripheral blood immune cell subsets.

“In summary, the combination of temozolomide and nivolumab showed promising activity in NEN, especially in lung and pancreatic NEN. This study included patients with both NET and NEC and activity was seen across the spectrum of differentiation in NEN. 

This study has several limitations, including its single-arm, single-institution nature (see link  below Supplementary Table S5) with relatively short follow-up. The study population was also heterogeneous, and studies of patient subsets are limited because of small numbers. Biomarker studies were further limited by missing samples predominantly driven by lack of sample collection during the COVID-19 pandemic. The timing of immune analysis at day 15 may also be impacted by myelosuppression of temozolomide. Therefore, the immune exploratory analyses should be considered hypothesis generating. Given the single-arm combination nature of the trial, it is not possible to interpret the contribution of each drug to response or synergy of the combination therapy. Although the response rate observed in this study—especially in lung NEN—is higher than expected with either agent given alone, this combination warrants further study though to determine efficacy of temozolomide, nivolumab, or the combination.

In conclusion, combination nivolumab and temozolomide demonstrated promising efficacy in NENs, especially in patients with lung and pancreas NEN.”

(full study info referenced below)