Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003.
Purpose: We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC).Patients and Methods: Patients with metastatic clear cell RCC who experienced progression...
| Published in: | Journal of Clinical Oncology Vol. 38; no. 11; pp. 1138 - 1147 |
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| Main Authors: | , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
American Society of Clinical Oncology
4/10/2020
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142612928&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142612928 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0732183X 20D jtl: Journal of Clinical Oncology issn: 0732183X maglogo: N pubinfo: dt: 4/10/2020 vid: 38 iid: 11 pid: 26892 pub: American Society of Clinical Oncology place: Alexandria, Virginia artinfo: ui: 142612928 142612928 NLM32097091 142612928 10.1200/JCO.19.02394 NLM32097091 142612928 ppf: 1138 ppct: 9 formats: tig: atl: Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003. aug: au: Dudek, Arkadiusz Z. Liu, Li C. Gupta, Shilpa Logan, Theodore F. Singer, Eric A. Joshi, Monika Zakharia, Yousef N. Lang, Joshua M. Schwarz, James K. Al-Janadi, Anas Alva, Ajjai S. affil: Division of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL sug: subj: Kidney Neoplasms Drug Therapy Carcinoma, Renal Cell Drug Therapy Antineoplastic Agents, Combined Therapeutic Use Carcinoma, Renal Cell Pathology Kidney Neoplasms Mortality Middle Age Neoplasm Metastasis Aged, 80 and Over Male Antibodies, Monoclonal Adverse Effects Female Aged Antibodies, Monoclonal Administration and Dosage Adult Kidney Neoplasms Pathology Carcinoma, Renal Cell Mortality Human Validation Studies Comparative Studies Evaluation Research Multicenter Studies Scales Middle Aged: 45-64 years Aged, 80 & over Aged: 65+ years Adult: 19-44 years Male Female ab: Purpose: We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC).Patients and Methods: Patients with metastatic clear cell RCC who experienced progression after at least one systemic therapy (phase Ib) or were treatment naïve (phase II) were enrolled. In phase Ib, pembrolizumab (200 mg) and bevacizumab (10 or 15 mg/kg) were given intravenously every 3 weeks. The primary end point for phase II was overall response rate (ORR). With an 80% statistical power and a type I error probability of 0.1, 48 patients were to be accrued to detect an ORR of 42%.Results: Thirteen patients (ages 33-68 years; median, 55 years) were enrolled in the phase Ib study. No dose-limiting toxicities were reported. Pembrolizumab 200 mg and bevacizumab 15 mg/kg were chosen for phase II. Forty-eight patients (ages 42-84 years; median age, 61 years; 33 males) were accrued for the phase II study. The primary end point was met, with the ORR reaching 60.9% (95% CI, 45.4% to 74.9%), consisting of 1 complete response (CR), 2 CRs in target lesions, 25 partial responses, 18 responses of stable disease, 2 unevaluable responses. Median progression-free survival was 20.7 months (95% CI, 11.3 to 27.4 months). Median overall survival was not reached at the median follow-up of 28.3 months. The most common treatment-related grade 3 toxicities were hypertension and proteinuria. There were two grade 4 toxicities: duodenal ulcer and hyponatremia. Presence of tumor-infiltrating T cells, but not programmed death-ligand 1 expression, in tumor tissue correlated with response.Conclusion: The combination of 200 mg of pembrolizumab and a 15 mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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