Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study

P. Giannatempo, D. Raggi, L. Marandino, M. Bandini, E. Farè, G. Calareso, M. Colecchia, A. Gallina, J. S. Ross, A. Alessi, A. Briganti, F. Montorsi, R. Madison, A. Necchi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Pembrolizumab is a new standard of care for patients with platinum-treated, metastatic urothelial carcinoma (UC). Nab-paclitaxel is active in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC. Patients and methods: PEANUT was an open-label, single-arm, phase II trial that included patients who had failed one or two chemotherapy regimens, including platinum chemotherapy. Biomarker analyses focused on programmed cell-death ligand-1 combined positive score (CPS) and comprehensive genomic profiling on tumor samples and circulating tumor DNA. Patients received 200 mg pembrolizumab on day 1 (D1), and 125 mg/m2 nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) according to RECIST (v1.1). The assumption was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between January 2019 and January 2020, the PEANUT study enrolled 70 patients: 24% had failed two prior systemic therapies; 31% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1; and 28.6% had liver metastases. After a median follow-up of 9.8 months, 40 patients have relapsed (57.1%). The median PFS was 5.9 months [95% confidence interval (CI) 3.1–11.5]. The confirmed objective response rate (ORR) was 38.6% (95% CI 27–51) with 17 partial responses and 10 complete responses (14.3%). The median duration of response was not reached. Five patients (7.1%) had ongoing responses lasting >12 months. The most common any-grade treatment-related adverse events included alopecia (71.4%), neutropenia (32.9%), and peripheral neuropathy (34.3%). Neither tumor mutational burden nor CPS was significantly associated with PFS at univariable analyses. The single-arm design of the trial was the major limitation. Conclusions: Pembrolizumab combined with nab-paclitaxel, as second- and third-line chemoimmunotherapy for metastatic UC, showed a favorable safety profile, durable PFS, and a clinically meaningful ORR in these preliminary analyses. This combination warrants additional randomized studies in earlier disease stages. ClinicalTrials.gov number: ClinicalTrials.gov NCT03464734; https://clinicaltrials.gov/ct2/show/NCT03464734.

Original languageEnglish
Pages (from-to)1764-1772
Number of pages9
JournalAnnals of Oncology
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 2020

Keywords

  • advanced urothelial carcinoma
  • chemoimmunotherapy combination
  • nab-paclitaxel
  • pembrolizumab
  • salvage therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

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