2370P - Updated results of PEANUT trial: Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma (mUC)

Background

Pembrolizumab (pembro) is approved for the II-line in mUC. In PEANUT trial (NCT03464734) we investigated the efficacy of the combination of pembro plus nab-paclitaxel after chemotherapy (CT) failure. Herein, a long-term follow-up (FUP) update and a post-hoc analysis are presented.

Methods

In an open-label, single-arm, phase 2 trial pts with mUC after failure of ≤2 platinum-based CT were enrolled. Pts received 200 mg pembro on D1, and 125 mg/m² nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression (PD) or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS).

Results

As of April 1, 2023, 11/70 (15.7%) pts enrolled are in CR after a median FUP of 45.5 mo (95% CI, 42.3 – 49.8). 5/70 (7.1%) completed 2-yrs of treatment. Median OS was 11.7 mo (95% CI, 8.27 – 17.2) and median PFS was 5.1 mo (95% CI, 4.1 – 7.37). The ORR was 47.1%. For CR or PR pts, median OS was 28.4 mo (95% CI, 16.2 – NA). OS rate was 19 (27.1%) at 46 mo. Treatment was discontinued due to toxicity in 12/70 (17.4%) pts: in 9/70 only nab-paclitaxel, in 3/70 both. After PD, 22/70 (32.4%) patients underwent further therapies. Levels of hemoglobin (HR 0.88; 95% CI, 0.76 – 1; p value 0.095) and NLR at baseline (HR 1.2; 95% CI, 1.1 – 1.3; p value 0.0032), discontinuation due to toxicity (HR 0.34; 95% CI, 0.14 – 0.79; p value 0.012) and subsequent therapy (HR 2.4; 95% CI, 1.3 – 4.4; p value 0.0033) appear to have a statistically significant impact in PFS. Instead, the primary (bladder vs UTUC) (HR 2.3; 95% CI, 1.1 – 4.7; p value 0.027), liver metastases (HR 2.4; 95% CI, 1.3 – 4.2; p value 0.0032), NLR at baseline (HR 1.2; 95% CI, 1.1 – 1.3; p value 0.0014) and discontinuation due to toxicity (HR 0.38; 95% CI, 0.16 – 0.89; p value 0.026) seem to have a greater influence on OS.

Conclusions

After nearly 4 years, the combination of pembrolizumab and nab-paclitaxel maintained clinically meaningful efficacy in pts with mUC that progressed after platinum-based CT. OS data and post-hoc analyzes are consistent with what has been published in the literature in this disease setting.

Clinical trial identification

NCT03464734.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale Tumori di Milano - Italy.

Funding

This study was partially supported by Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

E. Verzoni: Financial Interests, Personal, Principal Investigator: Janssen, Ipsen, MSD, Pfizer, Merck, Novartis. G. Procopio: Financial Interests, Personal, Advisory Board, consultant fees: Astellas, AstraZeneca, Bayer, BMS, Janssen, Ipsen, Merck, MSD, Novartis, Pfizer; Financial Interests, Institutional, Research Grant, research funding for no profit clinical trial: Ipsen. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Steering Committee Member: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Coordinating PI: Incyte; Financial Interests, Local PI: Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). P. Giannatempo: Financial Interests, Personal, Local PI: Merck, Janssen; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Funding: Ipsen. All other authors have declared no conflicts of interest.