Given the efficacy and safety demonstrated, there may be a role going forward for the pembrolizumab/nab-paclitaxel combination in earlier disease stages.
The combination of the PD-1 inhibitor pembrolizumab (Keytruda) and the chemotherapy nab-paclitaxel (Abraxane) showed clinically meaningful activity in patients with platinum-treated, locally advanced or metastatic urothelial carcinoma (UC), according to findings from the phase 2 PEANUT study.
In the study, salvage therapy with the combination induced an overall response rate (ORR) of 27%, comprising a 10% complete response (CR) rate and a 17% partial response rate. An additional 18% of patients achieved stable disease, with 17% of patients having progressive disease.
The median time to response was 1.4 months. At a median follow-up of 9.8 months, the median duration of response had not been reached. Twenty-four patients remained in response and continued to receive treatment, including 5 with responses lasting more than 12 months. The median progression-free survival (PFS) was 5.9 months (95% CI, 3.1-11.5) and the median overall survival (OS) had not yet been reached.
“PFS, ORR, and CR rate in particular were clinically meaningful and seemingly sustained after a noteworthy follow-up duration,” Andrea Necchi, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, reported at the at the 2020 European Association of Urology Virtual Congress.
Between February 2019 and January 2020, the study enrolled 70 patients with UC of the bladder or urothelium. The median patient age was 67 (range 60-73), 26% of patients were female, 69% of patients had an ECOG performance score of 0, and 31% had an ECOG performance score of 1.
Patient histology included pure UC (81%), UC and squamous cell carcinoma component (11%), UC and glandular component (4%), and other variants (3%). Smoking status comprised 19 never smokers, 10 current smokers, and 41 former smokers. The site of the primary tumor included the bladder (84.3%), upper urinary tract (14.3%), and urethra (1.4%).
Overall, 58.6% of patients had visceral disease, 22.9% had lung metastases, 28.6% had liver metastases, and 28.6% had bone metastases. Lymph node only disease occurred in 32.9% of patients and 13% of patients had a hemoglobin level <10 gr/dL. The Bellmunt scores were 0 (50%), 1 (29%), 2 (20%), and 3 (1%).
About three-fourths (76%) of patients had received 1 prior systemic regimen and 24% had received 2 prior systemic regimens. Prior neoadjuvant or adjuvant chemotherapy had been received by 39% of patients. Sixty-nine percent of patients had radical removal of their primary tumor, 29% had a history of previous non-muscle invasive UC, and 19% had previous BCG intravesical instillations.
All patients received pembrolizumab at 200 mg IV on day 1 and nab paclitaxel at 125 mg/m2 IV on days 1 and 8 of 3-week cycles. Treatment was received until loss of clinical benefit, unacceptable toxicity, patient or investigator decision to withdraw, or death. The primary end point was PFS per RECIST v1.1 and secondary end points were safety, ORR, duration of response, and OS.
Treatment-related grade 3/4 adverse events (AEs) occurred in 24.3% of patients, nab-paclitaxel–related grade 3/4 AEs occurred 22.9% of patients, and pembrolizumab-related grade 3/4 AEs occurred 4.3% of patients. Serious grade 3/4 AEs occurred in 10% of patients.
“The safety profile of the combination provided evidence that chemotherapy may still be an option to combine with an immunotherapy backbone,” said Necchi.
Given the efficacy and safety demonstrated in PEANUT, Necchi said there may be a role going forward for the pembrolizumab/nab-paclitaxel combination in earlier stages of disease, such as switch maintenance after first-line chemotherapy.
Necchi A, Raggi D, Bandini M, et al. Interim results of PEANUT: An open-label, single-arm, phase 2 study evaluating pembrolizumab plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC). 2020 European Association of Urology Virtual Congress. July 17-26, 2020. Abstract 1056.