ASCO 2018: Cctg BL12: Randomized Phase II Trial Comparing Nab-Paclitaxel to Paclitaxel in Patients with Advanced Urothelial Cancer Progressing On or After a Platinum Containing Regimen

Chicago, IL ( Nanoparticle albumin-bound paclitaxel (Nab-P) is an approved therapeutic agent for breast, lung and pancreatic cancer and has been found to be superior to paclitaxel alone. It is an is an injectable form of paclitaxel that is bound to albumin as a delivery vehicle. 

  • It is an albumin-bound, cremaphor free form of paclitaxel
  • It does not require steroid premedication
In patients who have failed platinum-based chemotherapy for metastatic urothelial carcinoma (mUC), options are limited. While immune checkpoint inhibitors have recently been approved in this space, they have been shown to have 15-20% objective response rates – implying that the remaining 75-85% of patients do not respond. Unfortunately, patients who don’t respond to platinum-based therapies and ICI’s have poor prognosis – and for the most part are treated with ineffective taxane and vinflunine chemotherapy (ORR ~10%). 

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:
UroToday ASCO2018 Cctg BL12 Study Design

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:

UroToday ASCO2018 Cctg BL12 Study Baseline Characteristics

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). 

UroToday ASCO2018 Cctg BL12 Study Anti tumor Activity

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