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 2 PEANUT Study

  • Pembrolizumab and nab-paclitaxel was evaluated in 70 patients with platinum-treated, metastatic urothelial carcinoma
  • The median PFS was 5.9 months, the objective response-rate was 38.6% and the median duration of response was not reached
  • Grade 3-4 treatment-related adverse events were observed in 17 patients (24.3%)
  • This study presented results from one of the first salvage chemoimmunotherapy regimens in advanced UC
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 2 trial that included patients who had failed 1 or 2 chemotherapy regimens, including platinum chemotherapy. Biomarker analyses focused on programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and comprehensive genomic profiling on tumor samples and circulating tumor DNA (ctDNA). Patients received 200 mg pembrolizumab on D1, and 125 mg/m 2 nab-paclitaxel, on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint 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 01/2019 and 01/2020, PEANUT study enrolled 70 patients: 24% had failed 2 prior systemic therapies; 31% had ECOG-performance status 1; 28.6% had liver metastases. After a median follow-up of 9.8 months, 40 pts 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 (TMB) nor CPS was significantly associated with PFS at univariable analyses. The single-arm design of the trial was the major limitation.

Conclusion Pembrolizumab combined with nab-paclitaxel, as second and third-line chemo-immunotherapy 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.

Authors: 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

Source: P. Giannatempo, D. Raggi, L. Marandino, F. Montorsi, R. Madison, A. Necchi et al. 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 2 PEANUT study." Annals of Oncology. 2020. DOI:https://doi.org/10.1016/j.annonc.2020.09.012.