Phase I/II Study of Hepatic Arterial Infusion of Nab-paclitaxel in Patients With Metastatic Melanoma to the Liver

Objectives: Hepatic arterial infusion (HAI) of cytotoxic chemotherapy is a strategy to deliver high dose of anticancer therapy to liver metastases that derive their blood supply from the hepatic artery. Metastatic melanoma (MM) has a high incidence of liver metastases, with uveal subtype in particular exhibiting a predilection for liver dissemination. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has demonstrated efficacy in MM and first-pass hepatic metabolism. Therefore, we hypothesized that HAI of nab-paclitaxel would deliver an effective dose of drug to the end organ of interest, with minimal systemic exposure. Patient and Methods: We performed a single-institution open-label phase I/II study of HAI of nab-paclitaxel in MM patients with liver metastasis. Patients received treatment every 21 days at 4 different dose levels. The primary objective of the phase I portion of the study was safety and determination of the maximum-tolerated dose. The primary objective of the phase II portion of the study was overall response rate per Response Evaluation Criteria In Solid Tumors (RECIST) 1.0. Results: A total of 30 patients were treated between 2009 and 2013, 16 of whom had uveal melanoma. The maximum-tolerated dose was 220 mg/m2 and 19 patients were treated at this dose. There was 1 patient (5%) with a partial response at this dose, and 8 patients (42%) with stable disease at this dose. Conclusions: HAI nab-paclitaxel demonstrates rare objective responses in melanoma patients with liver metastases. This treatment should be studied in combination with checkpoint blockade or other novel treatments to enhance meaningful responses but should not be considered effective monotherapy. Present address: Jesus Vera-Aguilera, MD, Mayo Clinic, Rochester, MN. Present address: Kevin B. Kim, MD, California Pacific Medical Center, San Francisco, CA. Present address: Jade Homsi, MD, The University of Texas Southwestern Medical Center, Dallas, TX. This manuscript discusses an unlabeled use for nab-paclitaxel. It is not FDA-approved for the treatment of metastatic melanoma. Abraxis Bioscience sponsored the study reported in this manuscript. This work was also supported by the NIH Cancer Center Support Grant P30CA016672. W.-J.H. reports clinical trial support from Bristol-Byers Squibb, Merck, Glaxo SmithKline, and Medimmune outside the submitted work. S.P.P. is an advisory board member for Castle Biosciences, a past advisory board member for OncoSec, a nonpromotional speaker for Merck, and reports clinical trial support from Bristol-Myers Squibb, Glaxo SmithKline, Novartis, and Reata outside the submitted work. K.B.K. reports clinical trial funding and speakers fees from Bristol-Myers Squibb outside the submitted work. P.H. is an advisory board member for Lion Biotechnologies and Immatics. The remaining authors declare no conflicts of interest. Reprints: Sapna P. Patel, MD, 1515 Holcombe Blvd, Unit 0430, Houston, TX 77030. E-mail: sppatel@mdanderson.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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