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Efficacy and Safety of nab-Paclitaxel vs Paclitaxel on Survival in Patients With Platinum-Refractory Metastatic Urothelial Cancer


Importance  Treatment options for platinum-refractory metastatic urothelial cancer (mUC) are limited, and outcomes remain poor. Nab-paclitaxel is an albumin-bound formulation of paclitaxel showing promising activity and tolerability in a prior single-arm trial.

Objectives  To evaluate the efficacy and safety of nab-paclitaxel vs paclitaxel in platinum-refractory mUC.

Design, Setting, and Participants  In this investigator-initiated, open-label, phase 2 randomized clinical trial conducted across Canada and Australia from January 2014 to April 2017, eligible patients had histologically confirmed, radiologically evident mUC of the urinary tract. Mixed histologic findings, except small cell, were permitted provided UC was the predominant histologic finding. All patients had received platinum-based chemotherapy either in the metastatic setting or were within 12 months of perioperative chemotherapy. Patients with prior taxane chemotherapy were not included. Patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2 and adequate organ function.

Interventions  Patients were randomized to nab-paclitaxel, 260 mg/m2, or paclitaxel, 175 mg/m2, every 3 weeks.

Main Outcomes and Measures  The primary end point was progression-free survival (PFS).

Results  Among 199 patients, median age was 67 (range, 24-88) years; 144 (72%) were men; 167 (84%) were ECOG PS 0-1; 59 (30%) had liver metastases; and 110 (55%) were within 6 months of prior platinum-based chemotherapy. At a median follow-up of 16.4 months, there was no significant difference between nab-paclitaxel vs paclitaxel for median PFS (3.4 months vs 3.0 months; hazard ratio [HR], 0.92; 90% CI, 0.68-1.23; 1-sided P = .31). Median overall survival was 7.5 months for nab-paclitaxel vs 8.8 months for paclitaxel (HR, 0.95; 90% CI, 0.70-1.30; 1-sided P = .40); and objective response rate (ORR) was 22% for nab-paclitaxel vs 25% for paclitaxel (P = .97). Grade 3/4 adverse events were more frequent with nab-paclitaxel (64/97 [66%]) compared with paclitaxel (45/97 [46%]), P = .009; but peripheral sensory neuropathy was similar (all grades, 72/97 [74%] vs 64/97 [66%]; grade 3/4, 7/97 [7%] vs 3/97 [3%]; P = .27). There were no apparent differences in scores for health-related quality of life.

Conclusions and Relevance  In this open-label, phase 2 randomized clinical trial of patients with platinum-refractory mUC, nab-paclitaxel had similar efficacy to paclitaxel; but worse toxic effects. The ORR with either taxane, however, was higher than previously reported and similar to those reported for the immune checkpoint inhibitors, suggesting that the taxanes remain a reasonable option in this setting.

Trial Registration  ClinicalTrials.gov Identifier: NCT02033993

Srikala S. Sridhar, MD1; Normand Blais, MD2; Ben Tran, MD3; et alM. Neil Reaume, MD4; Scott A. North, MD5; Martin R. Stockler, MD6; Kim N. Chi, MD7; Neil E. Fleshner, MD1; Geoffrey Liu, MD1; John W. Robinson, MD8; Som D. Mukherjee, MD9; Yasmin Rahim, MD10; Eric Winquist, MD11; Christopher M. Booth, MD12; Nghia Trung Nguyen, MD13; Emma K. Beardsley, MD14; Nimira S. Alimohamed, MD8; Gail T. McDonald, MSc15; Keyue Ding, PhD15; Wendy R. Parulekar, MD15

1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
3Peter MacCallum Cancer Centre, Victoria, Australia
4Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
5Cross Cancer Institute, Edmonton, Alberta, Canada
6NHMRC Clinical Trials Centre, Sydney, Australia
7British Columbia Cancer Agency Vancouver, British Columbia, Canada
8Tom Baker Cancer Centre, Calgary, Alberta, Canada
9Juravinski Cancer Centre, Hamilton, Ontario, Canada
10Stronach Regional Cancer Centre, Newmarket, Ontario, Canada
11London Health Sciences Centre, London, Ontario, Canada
12Department of Oncology, Queen’s University, Kingston, Ontario, Canada
13Hopital Charles-LeMoyne, Montreal, Quebec, Canada
14Frankston Hospital/Cabrini/Monash University, Parkdale, Australia
15Canadian Cancer Trials Group (CCTG), Queen’s University, Kingston, Ontario, Canada