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, 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
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.govNCT03464734; https://ichgcp.net/clinical-trials-registry/NCT03464734.
Keywords: advanced urothelial carcinoma; chemoimmunotherapy combination; nab-paclitaxel; pembrolizumab; salvage therapy.
Conflict of interest statement
Disclosure AN reports consulting for Merck, Astra Zeneca, Janssen, Incyte, Roche, Rainier Therapeutics, Clovis Oncology, Bayer, and Astellas/Seattle Genetics, Ferring, Immunomedics; grant/research support from Merck, Ipsen, and Astra Zeneca; travel expenses/honoraria from Roche, Merck, Astra Zeneca, and Janssen. RM and JSR are employees and stock owners of Foundation Medicine Inc. All other authors have no disclosures.
Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Source: PubMed