The 2022 ASCO annual meeting featured an oral abstract session on kidney and bladder cancer, including a presentation by Dr. Zesheng An discussing results of TRUCE-02, an open label, single-arm, phase II study of tislelizumab combined with nab-paclitaxel for high-risk non-muscle-invasive bladder carcinoma (NMIBC). Patients with multiple or tumors with large invasion areas which are incompletely resected with TURBT are typically recommended for radical cystectomy. The KEYNOTE-057 study has illuminated the efficiency of immune checkpoint inhibitors monotherapy in HR-NMIBC patients, with acceptable adverse events [1]. However, the role of PD-1/PD-L1 inhibitor in combination with chemotherapy in NMIBC patients remains unclear. At ASCO 2022, Dr. An and colleagues reported preliminary treatment efficiency, safety data, and exploratory work of the TRUCE-02 trial.
TRUCE-02 is a phase II study for NMIBC patients with incompletely resected tumor by TURBT. Patients that meet the criteria would receive tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks x 3 or 4 cycles followed by a comprehensive assessment including pathology, urine cytology, and radiographic follow-up. The trial schema for TRUCE-02 is as follows:
Biomarker analyses on peripheral blood, and at different time points of urine, and pre- and post-therapy tumor samples included:
- Peripheral blood: tissue and matched blood for next-generation sequencing for analysis of somatic mutations
- Urine specimen: whole genome sequencing and cfDNA sequencing
- Tumor biopsy: PD-L1 testing, whole exome sequencing, whole transcriptome sequencing
Eligibility included:
- Histopathological confirmed high-risk NMBIC, or HR-NMIBC as the major pathological components (>50%) defined as T1, high-grade Ta, or CIS
- The latest TURBT has been performed within 6 weeks, and tumor cells in urine exfoliation cytology within 2 weeks were visible
- ECOG 0-2
- Adequate bone marrow and hepatic function
- No contraindications to immunotherapy
The primary endpoint was complete response (absence of non-muscle-invasive bladder cancer or progressive disease). Secondary endpoints included (i) cystectomy-free survival (time from initiation of tislelizumab and date of radical cystectomy), (ii) duration of response (events from the onset of the first tumor assessment as complete or partial response to the first assessment of progressive disease or death from any cause), and (iii) incidence of serious adverse events and immune-related adverse events. From a statistical standpoint, the response rate of the experimental group was 41.2%, and the response rate of the control group was 20%. With an alpha of 0.05 and a power of 90%, the sample size was calculated to require 63 cases.
Between July 2020 and January 2022, 55 patients were enrolled with a median follow-up of 9 (range 3-16) months. Overall, 42 patients completed 3 or 4 treatment cycles and reached the primary endpoint. There were 23 patients that achieved a complete response (55%, 95% CI 43.6% to 74.4%), and the ORR was 60% (95% CI 45.2% to 74.8%). As a secondary endpoint, 28 patients remained cystectomy-free (66.7%) and the 12-month cystectomy-free survival rate was 62.7%. As follows is the Kaplan Meier curve for cystectomy-free survival:
Urine cytology had a diagnostic efficiency of 68.4% (95% CI 61.3% and 75.6%) and urine FISH had a diagnostic efficiency of 45.7% (95% CI 37.7% and 53.4%) before pathological assessment. As for PD-L1 expression, 47.3% (N = 9/19) of response patients (complete + partial response) were positive and 50% (N = 5/10) of unresponsive patients (progressive + stable disease) were positive. Dr. An and colleagues also noted that through sequencing, AR and TCF7L2 may be underlying markers that predict adverse outcomes for patients. Additionally, HRR mutations may predict a positive prognosis, which may predict the outcomes of this treatment plan. Grade 3-4 adverse events were lower than 2%.
Dr. An concluded his presentation discussing results of TRUCE-02, an open label, single-arm, phase II study of tislelizumab combined with nab-paclitaxel for high-risk NMIBC with the following take-home messages:
- Tislelizumab with nab-paclitaxel represents a novel treatment option with a satisfactory benefit in treating NMIBC
- This therapeutic regimen showed acceptable immune-related adverse events, with grade 3-4 adverse events less than 2%
- This therapeutic regimen showed promise for bladder preservation
- PD-L1 expression has no obvious correlation with the efficiency of this treatment plan
- Whole genome sequencing result also showed that there are mutation markers that may predict whether patients would benefit from this treatment
Presented By: Zesheng An, MD, Tianjin Medical University, Tianjin, China
Co-Authors: HaiTao Wang, Hailong Hu, Yuanjie Niu, Dawei Tian, Chong Shen, La Da, Zhouliang Wu, Gangjian Zhao, Diansheng Zhou, Yiduo Bai, Houyuan Chen
Affiliations: Tianjin Medical University Second Hospital, Tianjin, China, The second hospital of Tianjin Medical University, Tianjin, China, Tianjin Medical University Second Hospital, Tianjinshi, China, The Second Hospital of Tianjin Medical University, Tianjin, China
Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.
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