Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates

Autor: Renata R. Urban, Barbara A. Goff, Jennifer Childs, Katie M. Hitchcock-Bernhardt, Doreen Higgins, Andrew L. Coveler, Mary L. Disis, James Y. Dai, William R. Gwin, Tanya A. Wahl, Anna V. Tinker, Ron E. Swensen, Richard G Ancheta, Hania Shakalia, Kathryn F. McGonigle, John B. Liao, Sasha E. Stanton
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Cancer Research
medicine.medical_specialty
Anemia
medicine.medical_treatment
Immunology
Pembrolizumab
Antibodies
Monoclonal
Humanized
Gastroenterology
Carboplatin
chemistry.chemical_compound
Mice
Chemoimmunotherapy
Internal medicine
Cell Line
Tumor
Antineoplastic Combined Chemotherapy Protocols
medicine
Immunology and Allergy
Animals
Fallopian Tube Neoplasms
Humans
Peritoneal Neoplasms
RC254-282
Pharmacology
Clinical/Translational Cancer Immunotherapy
combination
Ovarian Neoplasms
business.industry
Area under the curve
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunotherapy
medicine.disease
Prognosis
drug therapy
medicine.anatomical_structure
female
Oncology
chemistry
genital neoplasms
Molecular Medicine
CD8-positive t-lymphocytes
immunotherapy
Ovarian cancer
business
Fallopian tube
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 9 (2021)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: BackgroundAnti-programmed death 1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies have shown modest activity as monotherapy in recurrent ovarian cancer. Platinum chemotherapies induce T-cell proliferation and enhance tumor recognition. We assessed activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer.Patients and methodsThis phase I/II, single-arm clinical trial studied concurrent carboplatin and pembrolizumab in recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer. Primary platinum refractory patients were excluded. Patients were treated after progression on subsequent non-platinum systemic therapy after becoming platinum resistant or refractory. Pembrolizumab 200 mg was given on day 1 and carboplatin area under the curve 2 on days 8 and 15 of a 3-week cycle until progression. Imaging was assessed by blinded independent review. PD-L1 expression was assessed by immunohistochemistry. Flow cytometry on peripheral blood mononuclear cells was performed for CD3, CD4, CD8, PD1, CTLA4 and Ki67.ResultsThe most common treatment-related adverse events were lymphopenia (18%) and anemia (9%) with most being grade 1 or 2 (93%). Of 29 patients treated, 23 patients were evaluable for best objective response: 10.3% (95% CI 2.2 to 27.4) had partial response (PR), 51.7% (95% CI 32.5 to 70.6) had stable disease (SD). 56.5% of patients had decreases in target lesions from baseline. All PD-L1-positive patients achieved PR (3/7, 42.8%) or SD (4/7, 57.2%). Median progression-free survival was 4.63 months (95% CI 4.3 to 4.96). Median OS was 11.3 months (95% CI 6.094 to 16.506). Peripheral CD8+PD1+Ki67+ T cells expanded after 3 (p=0.0015) and 5 (p=0.0023) cycles. CTLA4+PD1+CD8+ T cells decreased through the course of treatment up to the 12th cycle (p=0.004). When stratified by ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden at baseline, patients with a ratio ≥0.0375 who had a significantly longer median OS of 18.37 months compared with those with a ratio ConclusionsPembrolizumab with carboplatin was well-tolerated and active in recurrent platinum-resistant ovarian cancer. A ratio of peripheral T-cell exhaustion to radiographic tumor burden may identify patients more likely to benefit from this chemoimmunotherapy.Trial registration numberNCT03029598.
Databáze: OpenAIRE
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