PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers

Yiqian Gu; Ann Ly; Sara Rodriguez; Hanwei Zhang; Jiyoon Kim; Zhiyuan Mao; Ankush Sachdeva; Nazy Zomorodian; Matteo Pellegrini; Gang Li; Sandy Liu; Alexandra Drakaki; Matthew B Rettig; Arnold I Chin

doi:10.1016/j.xcrm.2024.101824

PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers

Cell Rep Med. 2024 Nov 19;5(11):101824. doi: 10.1016/j.xcrm.2024.101824. Epub 2024 Nov 12.

Authors

Yiqian Gu¹, Ann Ly², Sara Rodriguez², Hanwei Zhang², Jiyoon Kim³, Zhiyuan Mao⁴, Ankush Sachdeva², Nazy Zomorodian², Matteo Pellegrini⁵, Gang Li⁶, Sandy Liu⁷, Alexandra Drakaki⁸, Matthew B Rettig⁹, Arnold I Chin¹⁰

Affiliations

¹ Department of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁸ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁹ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; The VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
¹⁰ Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: arnoldchin@mednet.ucla.edu.

Abstract

Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.63, 1.00) for cohort 1 and 57% (95% CI: 0.30, 1.00) for cohort 2. Treatment is tolerated well with grade 3 or higher adverse events occurring in 40% of patients with no deaths or treatment cessation secondary to toxicity. Single-cell and T cell receptor sequencing of serial peripheral blood samples reveals clonal expansion of diverse T cell repertoire correlating with progression-free survival. Our results demonstrate promising efficacy and safety of this treatment combination and support future investigation of this biomarker. This study was registered at ClinicalTrials.gov (NCT03582475).

Keywords: PD-1 blockade; T cell receptor sequencing; clinical trial; immunochemotherapy; neuroendocrine prostate cancer; single-cell sequencing; small cell bladder cancer; small cell cancers.

Publication types

Clinical Trial, Phase I

MeSH terms

Adult
Aged
Antibodies, Monoclonal, Humanized / therapeutic use
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Carcinoma, Neuroendocrine / drug therapy
Carcinoma, Neuroendocrine / mortality
Carcinoma, Neuroendocrine / pathology
Carcinoma, Small Cell / drug therapy
Carcinoma, Small Cell / pathology
Cisplatin* / therapeutic use
Female
Humans
Immune Checkpoint Inhibitors / therapeutic use
Male
Middle Aged
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
Prostatic Neoplasms* / drug therapy
Prostatic Neoplasms* / pathology
Urinary Bladder Neoplasms* / drug therapy
Urinary Bladder Neoplasms* / pathology

Substances

Cisplatin
Programmed Cell Death 1 Receptor
pembrolizumab
Antibodies, Monoclonal, Humanized
PDCD1 protein, human
Immune Checkpoint Inhibitors

Associated data

ClinicalTrials.gov/NCT03582475