Abstract 1988
Background
Neuroendocrine carcinoma of the uterine cervix (NEC) is a rare cervical malignancy, accounting for 0.9% of all cervical carcinomas. Cervical NEC is a high-grade cancer with an aggressive clinical course and poor outcome. Given that no target therapy has been approved yet for NEC, we explored novel targetable biomarkers in a large cohort of NEC of the cervix.
Methods
Sixty-two NEC of the cervix were profiled for biomarkers of targeted therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), tropomyosin receptor kinases (NTRK1/2/3 gene fusions), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays.
Results
The study included 36 primary and 26 metastatic cervical NEC. The mean patient’s age was 43.6 years (range, 24-82 years). DLL3 expression was observed in 81% of the cases with 49% of cases expressing diffusely (≥50% of positive cancer cells) DLL3 protein. DLL3 expression was inversely correlated with commonly observed mutations: PIK3CA (7/47) (p = 0.018) and PTEN mutations (5/40) (p = 0.006). Other frequently seen mutations (TP53 17%, KRAS 11% and CTTNB1 5%) were not associated with DLL3 expression. PD-L1 expression, high TMB and MSI-H were seen in single cases. Although NTRK protein expression was observed in 21% of the cases, none of these had confirmatory NTRK gene fusions. TROP-2 and FOLR1 were negative in all tested cases.
Conclusions
DLL3 protein and PIK3CA/PTEN pathway genes may be potential therapeutic targets for a substantial proportion of the patients NEC of the cervix. Based on I-O biomarkers status, the patients with cervical NEC are less likely to benefit from immune checkpoint inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Arguello: Full / Part-time employment: Caris Life Sciences. E. Contreras: Full / Part-time employment: Caris Life Sciences. Z. Gatalica: Full / Part-time employment: Caris Life Sciences. All other authors have declared no conflicts of interest.
Resources from the same session
4413 - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF trial
Presenter: Ghassan Abou-Alfa
Session: Poster Display session 2
Resources:
Abstract
4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Lorenza Rimassa
Session: Poster Display session 2
Resources:
Abstract
5509 - A Randomized Controlled, Open label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine versus Gemcitabine alone in Patients with Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment (NCT03126435)
Presenter: Li-Tzong Chen
Session: Poster Display session 2
Resources:
Abstract
1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.
Presenter: Sylvie Lorenzen
Session: Poster Display session 2
Resources:
Abstract
2392 - GLOW: Randomized Phase 3 Study of Zolbetuximab + CAPOX Compared With Placebo + CAPOX as First-line Treatment of Patients With CLD18.2⁺/HER2⁻ Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Manish Shah
Session: Poster Display session 2
Resources:
Abstract
5217 - PRODIGE67_UCGI33 ARION: Association of Radiochemotherapy and Immunotherapy for the treatment of unresectable Oesophageal caNcer: a comparative randomized phase II trial
Presenter: Rosine Guimbaud
Session: Poster Display session 2
Resources:
Abstract
1726 - Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Presenter: Kenro Hirata
Session: Poster Display session 2
Resources:
Abstract
2279 - FRONTiER: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Presenter: Shun Yamamoto
Session: Poster Display session 2
Resources:
Abstract
4912 - A phase Ib/II study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined With mXELOX as First-line Therapy for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Jiafu Ji
Session: Poster Display session 2
Resources:
Abstract
3780 - Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Presenter: Salah-Eddin Al-Batran
Session: Poster Display session 2
Resources:
Abstract