Efficacy of Checkpoint Inhibitors in Neuroendocrine Neoplasms

2020 Year in Review - Neuroendocrine Tumors —January 9, 2021

Results of a retrospective analysis showed that checkpoint inhibitors as monotherapy had limited clinical benefit in patients with grade 3 neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs), and modest benefit when combined with another checkpoint inhibitor or chemotherapy.

To further characterize the treatment outcomes and responses achieved with immune checkpoint inhibitors in high-grade neuroendocrine neoplasms (NENs), a retrospective cohort study was conducted in patients with grade 3 NETs or NECs, which are distinct NENs; the results of this study were reported at the 2020 North American Neuroendocrine Tumor Society Annual Symposium.

The study included all patients aged ≥18 years, with a diagnosis of NEN at the Mayo Clinic between 2000 and 2020, who were treated with checkpoint inhibitors as monotherapy or combined with other checkpoint inhibitors or cytotoxic chemotherapy. Retrospective tumor response assessment and imaging interpretation was conducted to confirm results. Primary end points were objective response rate (ORR), progression-free survival (PFS), overall survival, and disease control rate.

A total of 46 eligible patients with NEC were identified; of these, 11 were treated with checkpoint inhibitor monotherapy (pembrolizumab, nivolumab, or atezolizumab), 15 patients were treated with dual checkpoint inhibitors (nivolumab + ipilimumab), and 20 patients received checkpoint inhibitors + chemotherapy (platinum/etoposide). Five patients with grade 3 NETs who had received checkpoint inhibitor monotherapy were also identified.

Among patients who received checkpoint inhibitor monotherapy, the median PFS was 2.1 months (range, 0.5-4.6 months; ORR, 0%), which was similar to the grade 3 NET cohort (median PFS, 2.9 months; ORR, 0%). Patients with NECs who received checkpoint inhibitors plus chemotherapy achieved an ORR of 36% and a median PFS of 4.2 months (1.6 months-not reached [NR]), whereas those who had received dual checkpoint inhibitor therapy achieved an ORR of 11% and a median PFS of 3.5 (1.4-NR) months.

Based on the results of this retrospective analysis, checkpoint inhibitors were associated with limited clinical benefit as monotherapy in patients with grade 3 NETs or NECs, with modest benefit when combined with another checkpoint inhibitor or chemotherapy.

Source: Gile J, et al. North American Neuroendocrine Tumor Society 2020 Annual Symposium; October 1-3, 2020. Abstract C6.

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Last modified: January 11, 2021

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