Durable Objective Response to Lurbinectedin in Small Cell Bladder Cancer with TP53 Mutation: A Molecular-Directed Strategy

Authors

Mohammad Jad Moussa
Jaanki Khandelwal
Nathaniel R Wilson
Sagar A Naik
Vivek Subbiah
Matthew T Campbell
Pavlos Msaouel
Parminder Singh
Omar Alhalabi

Publication Date

6-13-2024

Journal

Current Oncology

Abstract

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes.

Keywords

Humans, Carbolines, Urinary Bladder Neoplasms, Heterocyclic Compounds, 4 or More Rings, Mutation, Tumor Suppressor Protein p53, Male, Carcinoma, Small Cell, Heterocyclic Compounds, 3-Ring, Antineoplastic Agents, Middle Aged, lurbinectedin, small cell bladder cancer, neuroendocrine carcinoma of the bladder, targeted therapy, urothelial carcinoma, next-generation sequencing, transcription factors

Comments

Data Availability Statement

PMID: 38920737