Dynamic biomarker and imaging changes from a phase II study of pre- and post-surgical sunitinib.
dc.contributor.author | Welsh, Sarah | |
dc.contributor.author | Thompson, Nicola | |
dc.contributor.author | Warren, Anne | |
dc.contributor.author | Priest, Andrew N | |
dc.contributor.author | Barrett, Tristan | |
dc.contributor.author | Ursprung, Stephan | |
dc.contributor.author | Gallagher, Ferdia | |
dc.contributor.author | Zaccagna, Fulvio | |
dc.contributor.author | Stewart, Grant | |
dc.contributor.author | Fife, Kate M | |
dc.contributor.author | Matakidou, Athena | |
dc.contributor.author | Machin, Andrea J | |
dc.contributor.author | Qian, Wendi | |
dc.contributor.author | Ingleson, Victoria | |
dc.contributor.author | Mullin, Jean | |
dc.contributor.author | Riddick, Antony CP | |
dc.contributor.author | Armitage, James N | |
dc.contributor.author | Connolly, Stephen | |
dc.contributor.author | Eisen, Tim | |
dc.date.accessioned | 2021-11-03T07:11:23Z | |
dc.date.available | 2021-11-03T07:11:23Z | |
dc.date.issued | 2021-09-22 | |
dc.identifier.issn | 1464-4096 | |
dc.identifier.other | bju15600 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/330219 | |
dc.description | Funder: Pfizer; Id: http://dx.doi.org/10.13039/100004319 | |
dc.description.abstract | OBJECTIVE: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial. PATIENTS AND METHODS: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50 mg once daily sunitinib for 12 days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12 days. Computed tomography imaging was performed at baseline and post-surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE-MRI of the tumour following pre-surgery sunitinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Translational and imaging endpoints were exploratory. RESULTS: A total of 14 patients received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7-84.8%). The median OS was 33.7 months and median PFS was 15.7 months. Amongst those achieving a PR or CR, the median response duration was 8.7 months. No unexpected surgical complications, sunitinib-related toxicities, or surgical delays occurred. Within the translational endpoints, pre-surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation-31 (CD31), Ki67, circulating vascular endothelial growth factor-C (VEGF-C), and transfer constant (KTrans , measured using DCE-MRI; all P < 0.05). There was a trend for improved OS in patients with high baseline plasma VEGF-C expression (P = 0.02). Reduction in radiological tumour volume after pre-surgical sunitinib correlated with high percentage of solid tumour components at baseline (Spearman's coefficient ρ = 0.69, P = 0.02). Conversely, the percentage tumour volume reduction correlated with lower baseline percentage necrosis (coefficient = -0.51, P = 0.03). CONCLUSION: Neoadjuvant studies such as the NeoSun can safely and effectively explore translational biological and imaging endpoints. | |
dc.language | en | |
dc.publisher | Wiley | |
dc.subject | Original Article | |
dc.subject | Original Articles | |
dc.subject | neoadjuvant therapy | |
dc.subject | renal cell carcinoma | |
dc.subject | nephrectomy | |
dc.subject | sunitinib | |
dc.title | Dynamic biomarker and imaging changes from a phase II study of pre- and post-surgical sunitinib. | |
dc.type | Article | |
dc.date.updated | 2021-11-03T07:11:23Z | |
prism.publicationName | BJU Int | |
dc.identifier.doi | 10.17863/CAM.77661 | |
dcterms.dateAccepted | 2021-09-02 | |
rioxxterms.versionofrecord | 10.1111/bju.15600 | |
rioxxterms.version | AO | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.contributor.orcid | Welsh, Sarah [0000-0001-5690-2677] | |
dc.contributor.orcid | Warren, Anne [0000-0002-1170-7867] | |
dc.contributor.orcid | Priest, Andrew N [0000-0002-9771-4290] | |
dc.contributor.orcid | Barrett, Tristan [0000-0002-1180-1474] | |
dc.contributor.orcid | Ursprung, Stephan [0000-0003-2476-178X] | |
dc.contributor.orcid | Gallagher, Ferdia [0000-0003-4784-5230] | |
dc.contributor.orcid | Stewart, Grant [0000-0003-3188-9140] | |
dc.contributor.orcid | Fife, Kate M [0000-0002-1880-9049] | |
dc.contributor.orcid | Eisen, Tim [0000-0001-9663-4873] | |
dc.identifier.eissn | 1464-410X | |
pubs.funder-project-id | Cancer Research Uk (None) | |
pubs.funder-project-id | Cancer Research UK (C12912/A27150) | |
pubs.funder-project-id | Cancer Research UK (C19212/A29082) | |
pubs.funder-project-id | MRC (MR/T024097/1) | |
cam.issuedOnline | 2021-11-02 |
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