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

Abstract

IMPORTANCETreatment 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 PARTICIPANTSIn 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/m 2 , or paclitaxel, 175 mg/m 2 , every 3 weeks. MAIN OUTCOMES AND MEASURESThe 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 RELEVANCEIn 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.

Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study

“…In this study, nab-paclitaxel showed higher rates of all-cause grade 3e4 toxicities, including peripheral sensory neuropathy (all grades peripheral neuropathy was 74% for nab-paclitaxel versus 66% paclitaxel; grade 3e4 was 7% versus 3%). 14 Therefore, the main result of the PEANUT trial at this point is that taxanebased chemotherapy may still be a valid option for combination with checkpoint blockade, and using standard paclitaxel as a backbone therapy could result in an even better tolerated combination. Our chemoimmunotherapy combination was noteworthy in less pretreated patients with good prognostic factors, whereas combinations of immunotherapeutic agents or EV yield the potential to rescue an additional proportion of patients we were unable to rescue in this study.…”

Adverse Event Profile for Nanoparticle Albumin-Bound Paclitaxel Compared With Solvent-Based Taxanes in Solid-Organ Tumors: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…Nine trials (75%) were evaluated in breast cancer, 1 (8.3%) in NSCLC, 1 (8.3%) in urothelial cancer, and 1 (8.3%) in gastric cancer. 7,[20][21][22][23][24][25][26][27][28][29][30][31] Most trials investigated nab-paclitaxel as a single agent; however, 2 trials combined nab-paclitaxel with other agents (bevacizumab and carboplatin). There were 4 trials investigating nab-paclitaxel monotherapy in different doses, whereas the other 6 trials investigated a single dose.…”

Metastatic Urothelial Cancer: a rapidly changing treatment landscape

“…There are, however, two randomized trials worthy of attention: a phase III study, comparing vinflunine to best supportive care (BSC) alone, 60 and a phase II trial, comparing paclitaxel to nab-paclitaxel. 62 …”

“…Paclitaxel is a well-known and safe drug and is relatively inexpensive, with RRs observed in a quarter of the patients; it therefore remains a potential option in further lines of treatment. 62 In jurisdictions without access to novel therapies, paclitaxel remains a viable option in the post-platinum setting, with RRs at least similar to that seen with second line immunotherapy.…”

“…Definitions may vary according to the tumor site, but it is generally described as ‘a solitary or a few detectable metastatic lesions of a small size that are generally confined to a single or a few organs’. 62 The number of metastatic lesions that would fit the definition normally varies between 3 and 5, but remains an area of controversy. 64 , 65 This entity has increasingly gained attention due to the availability of new therapeutic options that are safe and non-invasive/minimally invasive, which may lead to long-term survival and, in some cases, cure.…”