Retrospective non-comparative single-center study of platinum-based regimen efficacy in the 1^st line therapy of high-grade neuroendocrine carcinomas of gynecologic tract

Introduction. Neuroendocrine carcinomas (NEC) of gynecologic tract are rare and aggressive tumors for which there are currently no standardized approaches to systemic therapy. Platinum-based chemotherapy regimens are the main treatment method, but data on their efficacy are limited to a few retrospective studies.

Aim. To evaluate the efficacy of platinum-based chemotherapy as first-line treatment for patients with metastatic gynecologic NEC, as well as the prognostic role of tumor histology, tumor location, disease extent, frequency of second-line therapy, and progression-free survival (PFS).

Materials and methods. A retrospective analysis was conducted of the efficacy of platinum-based chemotherapy as first-line therapy for primary metastatic or recurrent (with a platinum-free interval ≥12 months) NEC of gynecologic tract at the N. N. Blokhin National Medical Research Centre for Oncology in 2017–2024.

Results. The most common site of primary tumor was the cervix (n = 18; 62.1 %), 5 patients had ovarian NEC (17.2 %), 3 had uterine NEC (10.3 %), 2 had vulvar NEC (6.9 %), and 1 case of vaginal NEC was diagnosed (3.4 %). In 15 patients (51.7 %), the disease was detected at stage IV, and in 14 (48.3 %), progression was noted after primary treatment with a platinum-free interval of ≥12 months. Small-cell histological type was detected in 17 patients (58.6 %), large-cell in 12 of 29 (41.4 %). The frequency of high microsatellite instability (MSI) cases was 13.3 % (2 out of 15 examined), and positive expression of somatostatin receptors 2 and / or 5 (SSTR) was found in 33.3 % (4 out of 12 examined). In most cases, etoposide + cisplatin / carboplatin regimens were used (n = 25; 86.2 %), and 4 patients (13.8 %) received the paclitaxel + carboplatin regimen. The objective response rate was 44.8 %; the median PFS was 7.5 months (95 % confidence interval (CI) 2.9–12.1), median overall survival (OS) was 14 months (95 % CI 13–16.2). Disease control ≥6 months was achieved in 15 (51.7 %) patients, ≥12 months in 6 (20.7 %). Peritoneal carcinomatosis was significantly associated with worse PFS (hazard ratio 4.37; p = 0.01), and ECOG status 1–2 was associated with worse OS (hazard ratio 3.4; p = 0.01). No statistically significant differences in survival were found between histological types.

Conclusion. First-line platinum-based chemotherapy demonstrates efficacy comparable to previously published data in metastatic NEC of gynecologic tract. The high frequency of MSI-high cases justifies its routine measurement. The expression of somatostatin receptors is of interest for further study as a prognostic and therapeutic marker.