ASCO 2020: Final Results of PEANUT: Pembrolizumab and Nanoparticle Albumin-Bound Paclitaxel as Salvage Therapy for Metastatic Urothelial Carcinoma

(UroToday.com) Chemoimmunotherapy combinations have proven beneficial for patients with metastatic lung cancer with several approvals such as combination carboplatin-pembrolizumab-pemetrexed for patients with adenocarcinoma and carboplatin-paclitaxel–pembrolizumab for patients with squamous cell carcinoma of the lung.  This study evaluates the combination of chemotherapy and pembrolizumab for metastatic urothelial carcinoma in the second line setting.

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Data on 70 patients were presented at ASCO 2020. Patients received pembrolizumab on day 1 and nab-paclitaxel on days 1 and 8 every 3 weeks. The majority of patients were male with a median age of 69 years old.  This is a heavily pretreated population, 25% of patients had 2 or more prior lines of systemic therapy.  33% of patients had liver metastases.  

The objective response rate in this cohort was 39% with 10 complete responses (14.3%).  The median duration of responses has not been reached and 7% of patients have greater than 1 year of response.

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In terms of safety, 30% of patients had grade 3 treatment-related adverse events. The most common treatment-related adverse event was alopecia, followed by neutropenia, followed by fatigue.
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TMB was not associated with progression-free survival on unitary analysis. For patients with PDL1 CPS>10%, 7/9 patients had an objective response.
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Genomic analysis revealed that 8/10 patients with PI3KCA mutations in 6/10 patients with RB1 alterations responded.
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The expected objective response rate to second-line immunotherapy in patients with metastatic bladder cancer is in the range of 20 to 25%. CheckMate 275 (Nivolumab) had an objective response rate of 20%, KEYNOTE-045 (pembrolizumab) had an objective response rate of 21%.   This study had an impressive objective response rate of 39% with 14% achieving a CR.  These data support expanding this study and perhaps evaluating this in the frontline setting against the current standard of care therapies.  Combination chemoimmunotherapy has also shown promise with Enfortumab plus pembrolizumab which demonstrated an objective response rate of 73% (EV-103, GU ASCO 2020) – these chemo-immunotherapy combinations may be key to improving the objective response rates to single-agent immunotherapy. The key will be determining which therapies provide not only the best response rate but also the most durable and long term follow up is important. 

Presented by: Patrizia Giannatempo, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Written by: Jason Zhu, MD, Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu, at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.

Related Content: 
Read: Is Chemoimmunotherapy Prime Time for First-Line Metastatic Urothelial Carcinoma?

 

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