Multicenter Analysis of Treatment Outcomes for Well-Differentiated Grade 3 NETs

Results of a retrospective analysis of first-line chemotherapy regimens indicate that non–platinum/etoposide regimens may provide a significant progression-free survival (PFS) benefit versus platinum/etoposide regimens for patients with grade 3 neuroendocrine tumors (NETs).

Well-differentiated grade 3 NETs may not respond well to common platinum-based chemotherapy regimens; however, potential alternative treatment regimens, including those that are temozolomide- or streptozotocin-based, and the combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX), have only been studied in the second-line setting. Therefore, a multicenter, retrospective analysis was performed to evaluate treatment outcomes with different chemotherapy regimens administered as first-line therapy for patients with grade 3 NETs; results of this analysis were reported at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

An analysis of all patients with grade 3 NETs in the neuroendocrine neoplasm databases from 3 German cancer centers was performed. All histopathologic findings were confirmed to be consistent with the most current World Health Organization classification.

The retrospective review identified a total of 131 patients with grade 3 NETs, with a median age of 57 years (range, 14-81 years). The primary tumor site was predominantly in the pancreas (69.5%), with metastatic disease in 94.7% of patients; 15.3% of patients had prior grade 1/2 NET diagnosis. The median Ki67 was 30% (range, 21%-70%). Systemic first-line therapy included platinum/etoposide (26%), FOLFOX (27.5%), temozolomide-based (primarily temozolomide + capecitabine, 26%), streptozotocin-based (14.5%), and other approaches, including everolimus, sunitinib, somatostatin analogs, peptide receptor radionuclide therapy, and multimodal combination (9.9%).

In the total population, with a median follow-up of 20.4 months, median overall survival was 138.1 months. The overall response (ORR) and disease control rate (DCR) were highest for the FOLFOX regimen (ORR, 52.8%; DCR, 80.6%); the ORR for the platinum/etoposide regimen was 35.3%; it was 28.6% for the temozolomide-based regimen, 47.4% for the streptozotocin-based regimen, and 20.0% for other approaches; the DCR was 67.6%, 66.7%, 68.4%, and 73.3%, respectively. The median PFS for the platinum/etoposide regimen was 5.2 months; PFS was 6.0 months for the FOLFOX regimen (P = .164), 12.0 months for the temozolomide-based regimen (P = .059), 5.7 months for the streptozotocin-based regimen (P = .519), and 14.1 months for other approaches (P = .003). Compared with the platinum/etoposide-treated cohort, patients who received non–platinum/etoposide regimens showed a significantly prolonged PFS (9.0 vs 5.2 months; P = .011). In total, 89 patients received second-line systemic therapy, including platinum/etoposide; FOLFOX; temozolomide-based; folinic acid, fluorouracil, and irinotecan; and other approaches. The median PFS was 5.3 months in the second-line setting.

The results of this multicenter, retrospective analysis of different chemotherapy regimens for grade 3 NETs indicate that non–platinum/etoposide regimens may provide a significant PFS benefit as first-line therapy compared with platinum/etoposide; in particular, FOLFOX yielded the highest ORR, and the temozolomide-based regimen was associated with the longest PFS.

Source: Apostolidis L, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4607.