Selinexor in combination with standard chemotherapy in patients with advanced or metastatic solid tumors

Kyaw Z. Thein, Sarina A. Piha-Paul, Apostolia Tsimberidou, Daniel D. Karp, Filip Janku, Siqing Fu, Vivek Subbiah, David S. Hong, Timothy A. Yap, Jatin Shah, Denái R. Milton, Lacey McQuinn, Jing Gong, Yanyan Tran, Brett W. Carter, Rivka Colen, Funda Meric-Bernstam, Aung Naing

Research output: Contribution to journalLetterpeer-review

Abstract

Selinexor, an oral selective inhibitor of nuclear export (SINE), was demonstrated to hinder the DNA damage repair (DDR) system by reducing DDR proteins while enhancing the killing of cancer cells by DDR-based therapeutics in vivo studies. In this single-center, multi-arm phase 1b study, selinexor with carboplatin, doxorubicin and cyclophosphamide (DC), irinotecan with fluorouracil and folinic acid (FOLFIRI), irinotecan, and capecitabine and oxaliplatin (XELOX), were employed as separate parallel arms. Eligible patients have relapsed/ metastatic refractory solid tumors following standard therapy or addition of selinexor to systemic therapy was appropriate. Nineteen patients were treated in the 5 arms. Tumor types included were colorectal (n = 3), breast (n = 3), neuroendocrine (n = 2), ovarian (n = 2), and pancreas cancers (n = 2). All patients developed one treatment-related adverse events (TRAE). The most prevalent TRAE were thrombocytopenia (84%), nausea (68%), leukopenia (68%), neutropenia (63%), and fatigue (58%). The common grade 3/4 TRAE were neutropenia (42%), leukopenia (26%), and hyponatremia (21%). Three patients had dose-limiting toxicities (DLT) in 3 separate arms. Fourteen patients were evaluable for response. Although no patients achieved complete or partial response (CR or PR), seven patients attained stable disease (SD). Disease control rate (DCR) was 14%. The combination of oral selinexor with different standard chemotherapies showed limited clinical activity despite toxicity and DLT prevented further dose escalation. Optimizing supportive care, the utility of growth factors, and aggressive measures on antiemetics strategies remain tangible. Trial registration ClinicalTrials.gov Identifier: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495). Sponsor(s): Karyopharm Therapeutics

Original languageEnglish (US)
Article number59
JournalExperimental Hematology and Oncology
Volume10
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Capecitabine and oxaliplatin (XELOX)
  • Carboplatin
  • Doxorubicin and cyclophosphamide
  • FOLFIRI
  • Irinotecan
  • Selinexor (KPT 330)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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