Findings of a retrospective safety analysis suggest that the risk for severe myelotoxicity or opportunistic infections is rare in patients with advanced neuroendocrine tumors (NETs).
The capecitabine + temozolomide regimen is the standard of care for patients with advanced NETs; however, the risk for opportunistic infections and long-term myelotoxicity is a concern. To assess the risk for these adverse events (AEs) in a real-world setting, a retrospective analysis of a large patient cohort was performed; the results of this analysis were reported at the 2020 American Society of Clinical Oncology Virtual Scientific Program.
The retrospective chart review included all patients with advanced neuroendocrine neoplasms who were treated with capecitabine + temozolomide at the Moffitt Cancer Center between January 2008 and June 2019; other patients who initiated treatment at outside institutions were also included if they were prescribed treatment at appropriate doses and if complete records were available.
A total of 462 eligible patients were included in the analysis; the majority were male (55%) and the median age of the analysis population was 59 years. The primary tumor was predominantly located in the pancreas (71%), the majority had a Ki67 proliferation index of 3% to 50% (53%), 41% of patients had a grade 2 NET, and 79% of patients had well-differentiated tumors. The median starting dose of capecitabine was 658 mg/m2 and temozolomide was 180 mg/m2; ondansetron was administered prophylactically prior to temozolomide. A total of 113 patients required a dose reduction: 60 required dose reductions of both drugs, 38 required dose reductions of capecitabine, and 15 required dose reductions of temozolomide. In total, 16% of patients discontinued treatment because of AEs.
The incidence of grade 4 thrombocytopenia was 7%; a significantly higher proportion of females experienced grade 4 thrombocytopenia compared with males (10% vs 5%; P = .02). Similarly, of the 3% incidence of grade 4 neutropenia in all patients, 5% occurred in females and 1% in males (P = .004). The incidence of grade 4 lymphopenia was 3% and was similar between females and males. The only opportunistic infections reported were 5 cases of herpes zoster, as well as 1 case (0.2%) of suspected pneumocystis pneumonia in a patient receiving corticosteroids. With respect to secondary malignancies, 3 patients developed myelodysplastic or myeloproliferative disease; all 3 had also received prior peptide receptor radionuclide therapy with lutetium-dotatate.
Results of this retrospective analysis indicate that the risk for severe myelotoxicity or opportunistic infections is rare; however, indications that the risks for grade 4 thrombocytopenia and neutropenia are significantly increased in females compared with males suggest that gender-based dosing may be considered in advanced NETs.
Source: Al-Toubah TE, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4614.