The 2023 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Achille Bottiglieri discussing update results of the PEANUT trial assessing pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma. Notably, pembrolizumab is approved for the second line in metastatic urothelial carcinoma.1,2
In the PEANUT trial (NCT03464734), Dr. Bottiglieri and colleagues investigated the efficacy of the combination of pembrolizumab plus nab-paclitaxel after chemotherapy failure. At the ESMO 2023 annual congress, they presented a long-term follow-up update and a post-hoc analysis.
In an open-label, single-arm, phase 2 trial patients with metastatic urothelial carcinoma after failure of ≤2 platinum-based chemotherapy were enrolled. Patients received 200 mg pembrolizumab on D1, and 125 mg/m2 nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS). The trial schema for PEANUT is as follows:
Between January 2019 and April 2023, 70 patients were enrolled with the following baseline characteristics:
As of April 1, 2023, 11/70 (15.7%) patients enrolled are in complete response after a median follow-up of 48.6 months and 5/70 (7.1%) completed 2-years of treatment. The median OS was 11.0 months (95% CI, 7.6 – 16.8) and median PFS was 5.1 months (95% CI, 4.1 – 7.37) and ORR was 50.0%:
For complete response or partial response patients, median OS was 28.4 months (95% CI, 16.2 – NA), and OS rate was 19 (27.1%) at 46 months. Treatment was discontinued due to toxicity in 12/70 (17.4%) patients, including 9/70 receiving only nab-paclitaxel and in 3/70 receiving both treatments. After disease progression, 22/70 (32.4%) patients underwent further therapies. Hemoglobin level (HR 0.88, 95% CI 0.76 – 1) and neutrophil lymphocyte ratio at baseline (HR 1.20, 95% CI 1.1 – 1.3), discontinuation due to toxicity (HR 0.34, 95% CI 0.14 – 0.79), and subsequent therapy (HR 2.40, 95% CI 1.3 – 4.4) have a statistically significant impact in PFS. Furthermore, the primary tumor location (bladder vs upper tract urothelial carcinoma) (HR 2.30, 95% CI 1.10 – 4.70), liver metastases (HR 2.40, 95% CI 1.30 – 4.20), neutrophil lymphocyte ratio at baseline (HR 1.20, 95% CI 1.10 – 1.30), and discontinuation due to toxicity (HR 0.38, 95% CI, 0.16 – 0.89) seem to have a greater influence on OS.
Dr. Bottiglieri concluded this presentation discussing update results of the PEANUT trial assessing pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced, or metastatic urothelial carcinoma with the following concluding statements:
- After nearly 4 years, the combination of pembrolizumab and nab-paclitaxel maintained clinically meaningful efficacy in patients with metastatic urothelial carcinoma that progressed after platinum-based chemotherapy
- OS data and post-hoc analyzes are consistent with what has been published in the literature in this disease setting
Presented by: Achille Bottiglieri, IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
References:
- Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015-1026.
- Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): A multicentre, single-arm, phase 2 study. Lancet Oncol 2017;18(11):1483-1492.