- It is an albumin-bound, cremaphor free form of paclitaxel
- It does not require steroid premedication
Sridhar and colleagues have previously published their results of an open-label, single-group, two-stage study at five centers in Canada using Nab-P.1 In 48 patients, they had a 2.1% CR and 25.5% PR rate, resulting in an overall response of 27.7%. As such, it warranted additional evaluation.
They present the results of their phase II randomized trial of paclitaxel (P) vs. Nab-P in the mUC setting. The Canadian Cancer Trials Group led this multicenter international (Canada and Australia) randomized phase II trial comparing Nab-P 260mg/m2 IV q21 days to paclitaxel 175mg/m2 IV q21 days. All patients had advanced or mUC progressing after first line platinum-based therapy.
Study design is below:
They met the accrual goal of 199 patients between 2014 and 2017. Median follow-up 16.4 months. Patients were randomized 1:1 to both arms. Randomization was stratified according to ECOG, liver metastases, LN only mets, hemoglobin level and time ≤6mo or >6 mo from last platinum regimen.
Full comparison of the two arms (well-balanced) is below:
Patients had a median age 67y, 72% were males, 30% of patients had liver metastases, 84% were ECOG 0/1 and 55% were ≤6mo from last platinum therapy dose.
In terms of dose received: relative dose intensity ≥90% was 78% for Nab-P vs 67% for P. While getting more drug, the rate of Grade(Gr)3+ all causality AEs was 67% for Nab-P vs 46% for P (p = 0.009). There were no significant differences in mean scores in any domain of QOL between Nab-P and P.
In terms of oncologic outcomes, with median follow up 16.4 months, median progression-free survival (PFS) for Nab-P was 3.4 mo vs 3.0 mo for P (HR 0.92, 90%CI 0.68-1.23, p = 0.31). Median OS for Nab-P was 7.5mo vs 8.8 mo for P (HR 0.95, 90%CI 0.70- 1.30, p = 0.40).
Ultimately, despite promising early phase II results, the results of this head-to-head comparison demonstrate that Nab-P had similar oncologic efficacy to paclitaxel, but was also associated with a higher rate of Grade 3+ adverse events. Hence, it is not likely an appropriate substitution for paclitaxel in this disease space. While a negative study, it was important to report. Clinical Trial:
1. Ko YJ, Canil CM, Mukherjee SD, Winquist E, Elser C, Eisen A, Reaume MN, Zhang L, Sridhar SS.Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013 Jul;14(8):769-76. doi: 10.1016/S1470-2045(13)70162-1. Epub 2013 May 22.
Presented by: Srikala S. Sridhar, MD, FRCPC, Princess Margaret Cancer Centre, University Health Network
Co-Authors: Normand Blais, Ben Tran, M. Neil Reaume, Scott A. North, Martin R. Stockler, Kim N. Chi, Neil Eric Fleshner, Geoffrey Liu, John W Robinson, Som Mukherjee, Yasmin Rahim, Eric Winquist, Christopher M. Booth, Nghia Trung Nguyen, Emma Kate Beardsley, Nimira S. Alimohamed, Gail T McDonald, Keyue Ding, Wendy R. Parulekar
Author Information: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Department of Medical Oncology, Peter MacCallum Cancer Centre, Australia, Victoria, Australia; Ottawa Hospital Cancer Center, Ottawa, ON, Canada; University of Alberta Cross Cancer Institute, Edmonton, AB, Canada; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia; British Columbia Cancer Agency - Vancouver Centre, Vancouver, BC, Canada; Department of Surgery, Division of Urology, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Tom Baker Cancer Centre, Calgary, AB, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada; Stronach Regional Cancer Centre, Newmarket, ON, Canada; Western University and London Health Sciences Centre, London, ON, Canada; Queen's University, Kingston, ON, Canada; Hosp Charles-LeMoyne, Montreal, QC, Canada; Frankston Hospital/Cabrini/Monash University, Parkdale, Australia; Princess Margaret Cancer Centre, Toronto, ON, Canada; Canadian Cancer Trials Group, Cancer Research Institute, Queen's University, Kingston, ON, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
Read a Review on Abstracts 4503-4505 by Andrea B. Apolo, MD Nonimmunotherapy Strategies in Advanced Bladder Cancer