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ASCO 2020

ASCO 2020: Phase II Neoadjuvant Gemcitabine and Pembrolizumab for Locally Advanced Urothelial Cancer: Interim Results from the Cisplatin-Ineligible Cohort of GU14-188

(UroToday.com) The current standard of care for localized muscle-invasive bladder cancer involves cisplatin-based chemotherapy prior to cystectomy. However, 25-50% of patients bladder cancer are not candidates for cisplatin-based therapies, most commonly due to suboptimal renal function, but also due to baseline hearing loss and neuropathy. This study replaces cisplatin with pembrolizumab in combination with gemcitabine as neoadjuvant therapy for patients with muscle-invasive bladder cancer.


ASCO20_GU14-188.png



The study schema is shown above. Patients with cT2-4aN0M0 UC, with or without mixed histology who were cisplatin-ineligible were enrolled. 5 doses of neoadjuvant pembrolizumab were given starting on C1D8 of gemcitabine, which was given on days 1, 8, and 15 of a 28-day cycle (x 3 cycles). The primary endpoint of the study was pathologic muscle-invasive response rate defined as ≤pT1N0.

ASCO20_bladder_cancer.png

Baseline characteristics are above. The median age was 72 and the majority of patients had cT3/T4 disease. Most of the patients were eligible for cisplatin due to impaired renal function. Patients were also deemed cisplatin-ineligible due to hearing (30%) and neuropathy (12%).

ASCO20_pembrolizumab.png
The primary endpoint was reached in 52% of patients and a pathologic complete response was achieved and 45.2% of patients. The 12-month relapse-free survival was 67% and the 12-month disease-specific survival was 94%, with overall survival of 88.4% at 12 months.

ASCO20_pathologic_response.png

Treatment related adverse events included neutropenia, anemia, and thrombocytopenia.  Grade 3 immune related adverse events were noted.  5% of patients had pneumonitis, 3% had colitis, 3% had AST elevation.  2 patients did not have radical cystectomy secondary to progression.

ASCO20_TRAE.png

The pathologic complete response rate to standard of care gemcitabine and cisplatin is roughly 20 to 30%1. The data presented with neoadjuvant gemcitabine pembrolizumab compares favorably to gemcitabine and cisplatin and does not have the same renal function requirements as cisplatin-based chemotherapy. Of note, 11% (4/37) of patients developed grade 3 immune-related adverse event which led to treatment discontinuation in 3 of the patients. Neoadjuvant chemo-immunotherapy deserves further study based on this study for high-risk bladder cancer patients.

Presented by: Hristos Z. Kaimakliotis, MD, Assistant Professor of Urology, Indiana University School of Medicine, Indianapolis, IN

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.

References:

  1. Dash A, Pettus IV JA, Herr HW, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle‐invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 2008;113:2471-7.

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Clinical Trial Information: NCT02365766