A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer : Journal of Urology

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Adult Urology: Oncology: Adrenal/Renal/Upper Tract/Bladder

A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer

Tsung, Irene1,*; Green, Edward1; Palmbos, Phillip1; Sloan, Zachery2; Reichert, Zachery R.1; Vaishampayan, Ulka1; Smith, David C.1; Caram, Megan E. V.1; Yentz, Sarah1; Daignault-Newton, Stephanie2; Hurley, Laura2; Nguyen, Charles B.1; Kraft, Shawna3; Alva, Ajjai1

Author Information

1Department of Hematology and Oncology, Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan

2Oncology Clinical Trials Support Unit, Rogel Comprehensive Cancer Center, Ann Arbor, Michigan

3Department of Pharmacy, University of Michigan, Ann Arbor, Michigan

*Correspondence: University of Michigan, 1500 E. Medical Center Dr., C369 Med Inn Building, SPC 5848, Ann Arbor, Michigan 48109 telephone: 734-615-1623; [email protected]

Submitted June 10, 2022; accepted August 31, 2022; published November 1, 2022.

Disclosure: Dr Daignault-Newton is on the Statistician Board of The Journal of Urology®.

Support: This work was supported by Celgene/Bristol-Myers Squibb.

Conflict of Interest: Ajjai Alva has served in an advisory role to AstraZeneca, Merck, Pfizer, Bristol-Myers Squibb; received research funding through the institution from Genentech, Bristol-Myers Squibb, Merck Sharp & Dohme, Prometheus Laboratories, Mirati Therapeutics, AstraZeneca, Roche, Bayer, Progenics, Astellas Pharma, Arcus Biosciences, Celgene, Janssen; received Travel, Accommodations, Expenses from Merck and Bristol-Myers Squibb. Phillip Palmbos has received research funding through Roche and Immunomedics. Zachery R. Reichert has served in an advisory role to Dendreon; received research funding through the institution from AstraZeneca. Ulka Vaishampayan has served in an advisory role to Pfizer, Exelixis, Bayer, Bristol-Myers Squibb/Medarex, Merck Serono, Advanced Accelerator Applications, Alkermes, Helsinn Therapeutics; received research funding through Astellas Pharma, Exelixis, Bristol-Myers Squibb, Merck KGaA; participated in a speaker’s bureau for Pfizer, Bayer, Exelixis. David C. Smith has received research funding through the institution from Agensys, Incyte, Lilly, Novartis, Seattle Genetics, Bristol-Myers Squibb/Medarex, Genentech, Astellas Pharma, Bayer, ESSA, Roche, MedImmune. All remaining Authors have declared no conflicts of interest.

Ethics Statement: This study protocol was approved by the University of Michigan Institutional Review Board (IRB No. HUM00135166) and conducted in accordance with the Declaration of Helsinki.

The Journal of Urology 209(1):p 121-130, January 2023. | DOI: 10.1097/JU.0000000000002969
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Abstract

Purpose: 

Immune checkpoint inhibitor therapy and nab-paclitaxel have each shown efficacy in platinum-refractory advanced urothelial cancer. We conducted a single-arm phase 2 trial of the combination of nab-paclitaxel and pembrolizumab in platinum-refractory or cisplatin-ineligible advanced urothelial cancer (NCT03240016).

Materials and Methods: 

Eligible patients had RECIST 1.1 measurable and cisplatin-ineligible or platinum-refractory advanced urothelial cancer. Patients received nab-paclitaxel at starting dose of 125 mg/m2 intravenously on days 1 and 8 and pembrolizumab 200 mg intravenously on day 1 in 21-day cycles until progression, intolerable toxicity, or death. Nab-paclitaxel was permitted to be discontinued after 6 cycles. The nab-paclitaxel starting dose was reduced to 100 mg/m2 after planned interim analysis. Primary end point was overall response rate by RECIST 1.1. Secondary end points included safety/toxicity, duration of response, progression-free survival), and overall survival.

Results: 

Between February 2018 and April 2021, 36 response-evaluable patients were enrolled. There was an equal split of platinum-refractory and cisplatin-ineligible patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, median duration of response was 4.4 months (95% CI: 4.0-8.6), median progression-free survival 6.8 months (95% CI: 4.4-not reached), and median overall survival 18.2 months (95% CI: 10.6-not reached). Grade ≥3 adverse events occurred in 21/36 patients including fatigue (n=6) and anemia (n=4). Ten patients had immune-mediated adverse events.

Conclusions: 

The combination of nab-paclitaxel and pembrolizumab exhibited promising activity in advanced urothelial cancer and warrants further study in this population. After reduction in nab-paclitaxel starting dose, no unanticipated or unexpected toxicities emerged.

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© 2022 by American Urological Association Education and Research, Inc.

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