Durable clinical benefit from combination ipilimumab (IPI) and nivolumab (NIVO) in anti-PD-1 therapy resistant, platinum resistant metastatic urothelial carcinoma (mUC)
| Autor: | Mark J. Bluth, Phillip Wong, Grace Hettich, Niamh M. Keegan, Jessica M. Clement, Samuel Funt, Brooke Elizabeth Kania, Gopa Iyer, Dean F. Bajorin, Etay Ziv, Jonathan E. Rosenberg, Katherine S. Panageas, Asia S. McCoy, Jedd D. Wolchok, Colleen Anne Maher, Suresh G. Nair Md, Margaret K. Callahan |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research Therapy resistant medicine.medical_specialty Metastatic Urothelial Carcinoma business.industry Anti pd 1 Ipilimumab 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine medicine Single agent Nivolumab business 030215 immunology medicine.drug Platinum resistant |
| Zdroj: | Journal of Clinical Oncology. 37:481-481 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 481 Background: Overcoming resistance to anti-PD-1 therapy in UC patients (pts) is of major interest given the modest single agent response rates for pts with mUC. Herein we report the outcome of combined NIVO and IPI in pts who progressed on single agent NIVO. Methods: This prospective, open label, adaptive study treated platinum resistant mUC pts with NIVO monotherapy with the designated intent to add IPI at disease progression. RECIST 1.1 assessments were performed every 6 wks for 24 wks then every 12 wks. Primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS) and possible associations between clinical endpoints and tumor genomic characteristics. Next generation sequencing (NGS) was performed to assess DNA Damage Response (DDR) gene mutations and Tumor Mutation Burden (TMB). Results: To date, 21 pts who progressed after NIVO monotherapy have received IPI plus NIVO. ORRs to prior NIVO monotherapy were variable; partial response (PR = 4/21, 19%), stable disease (SD = 6/21, 29%) and progressive disease (PD = 11/21,52%). 57% (12/21) had visceral metastases. For IPI + NIVO the ORR was 19% (PR: n=4, CR: n=0) and duration of response >12 mo in a subset; 2 pts with PR remain on treatment (3+, 5+ mo), 1 pt has an ongoing PR (13+ months) after stopping treatment due to toxicity. Responding disease sites include node, liver and lung. Immune-related toxicity ≥ G3 seen in 9 pts (43%), of whom 4 (44%) had disease control (PR+SD≥3mo). No correlation detected between clinical outcome and TMB or DDR mutations. Conclusions: IPI plus NIVO responses can be seen in pts with NIVO resistance and the benefit from combined checkpoint blockade can be prolonged. Immune related toxicity frequently accompanied disease control. TMB and DDR were not associated with benefit in this small cohort; immune correlative analyses are ongoing. Clinical trial information: NCT02553642. [Table: see text] |
| Databáze: | OpenAIRE |
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