American Association for Cancer Research
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Supplementary table S1 from Low-dose Paclitaxel with Pembrolizumab Enhances Clinical and Immunologic Responses in Platinum-refractory Urothelial Carcinoma

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journal contribution
posted on 2024-02-26, 14:20 authored by Rhonda L. Bitting, Janet A. Tooze, Michael Goodman, Donald C. Vile, Jessica M. Brown, Christopher Y. Thomas, Morgan Neve, Mitra Kooshki, Safoa Addo, Pierre L. Triozzi, Purnima Dubey

MicroRNA levels are shown in responders and non-responders at baseline, after 3 cycles, and after 6 cycles of treatment. P-values suggest there is a trend toward differences in plasma miR 20a, miR 21, miR 125, miR 181, and miR 223 between responders and nonresponders. In the urine, only baseline levels of miR 21 suggest a difference.


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Single-agent checkpoint inhibition is effective in a minority of patients with platinum-refractory urothelial carcinoma; therefore, the efficacy of combining low-dose paclitaxel with pembrolizumab was tested. This was a prospective, single-arm phase II trial with key inclusion criteria of imaging progression within 12 months of platinum therapy and Eastern Cooperative Oncology Group ≤1. Treatment was pembrolizumab 200 mg day 1 and paclitaxel 80 mg/m2 days 1 and 8 of a 21-day cycle for up to eight cycles unless progression or unacceptable adverse events (AE). The primary endpoint was overall response rate (ORR) with overall survival (OS), 6-month progression-free survival (PFS), and safety as key secondary endpoints. Change in circulating immune cell populations, plasma, and urinary miRs were evaluated. Twenty-seven patients were treated between April 2016 and June 2020, with median follow-up of 12.4 months. Baseline median age was 68 years, with 81% men and 78% non-Hispanic White. ORR was 33% by intention to treat and 36% in imaging-evaluable patients with three complete responses. Six-month PFS rate was 48.1% [95% confidence interval (CI): 28.7–65.2] and median OS 12.4 months (95% CI: 8.7 months to not reached). Common ≥ grade 2 possibly-related AEs were anemia, lymphopenia, hyperglycemia, and fatigue; grade 3/4 AEs occurred in 56%, including two immune-mediated AEs (pneumonitis and nephritis). Responding patients had a higher percentage of circulating CD4+IFNγ+ T cells. Levels of some miRs, including plasma miR 181 and miR 223, varied in responders compared with nonresponders. The addition of low-dose paclitaxel to pembrolizumab is active and safe in platinum-refractory urothelial carcinoma. We found that combining pembrolizumab with low-dose paclitaxel may be effective in patients with urothelial carcinoma progressing on platinum chemotherapy, with favorable safety profiles.