In a phase 1b study, 15 patients with late-stage small cell bladder cancer or small cell/ neuroendocrine prostate cancer were treated with standard-of-care platinum chemotherapy and anti-PD-1 (pembrolizumab). At 24 months, PFS and OS were 50% and 71%, respectively. Treatment was generally safe, with grade 3+ adverse events in 40% of patients. Treatment led to expansion of pre-existing effector, activated, and cytotoxic T cell clonotypes, loss of naive, memory, and regulatory T cells, and detection of majority-novel clonotypes. T cell clonal expansion, but not baseline PD-L1 expression, TMB, or MSI status, correlated with PFS.
Contributed by Alex Najibi
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).
Author Info: (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 Medi
Author Info: (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 Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. (4) Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. (5) Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA. (6) Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. (7) Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. (8) Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. (9) 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. (10) 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. (11) Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. (12) 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. (13) 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. (14) 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.
