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.
advanced urothelial carcinoma
chemoimmunotherapy combination
nab-paclitaxel
pembrolizumab
salvage therapy
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
29
06
2020
revised:
27
08
2020
accepted:
16
09
2020
pubmed:
27
9
2020
medline:
7
1
2021
entrez:
26
9
2020
Statut:
ppublish
Résumé
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. 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/m 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. 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. ClinicalTrials.govNCT03464734; https://clinicaltrials.gov/ct2/show/NCT03464734.
Sections du résumé
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/m
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://clinicaltrials.gov/ct2/show/NCT03464734.
Identifiants
pubmed: 32979512
pii: S0923-7534(20)42462-7
doi: 10.1016/j.annonc.2020.09.012
pii:
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Antibodies, Monoclonal, Humanized
0
Platinum
49DFR088MY
pembrolizumab
DPT0O3T46P
Paclitaxel
P88XT4IS4D
Banques de données
ClinicalTrials.gov
['NCT03464734']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1764-1772Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
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.