Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: A subgroup analysis of the phase 3 KEYNOTE-045 trial Journal Article
| Authors: | Nishiyama, H.; Yamamoto, Y.; Sassa, N.; Nishimura, K.; Fujimoto, K.; Fukasawa, S.; Yokoyama, M.; Enokida, H.; Takahashi, K.; Tanaka, Y.; Imai, K.; Shimamoto, T.; Perini, R.; Frenkl, T.; Bajorin, D.; Bellmunt, J. |
| Article Title: | Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: A subgroup analysis of the phase 3 KEYNOTE-045 trial |
| Abstract: | Background: The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. Patients and methods: Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. Results: Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab. Conclusions: Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab. © 2019, The Author(s). |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; constipation; fatigue; neutropenia; cancer recurrence; advanced cancer; diarrhea; drug withdrawal; side effect; systemic therapy; treatment duration; paclitaxel; follow up; antineoplastic agent; cancer immunotherapy; progression free survival; quality of life; neutrophil count; sensory neuropathy; anemia; leukopenia; nausea; randomized controlled trial; stomatitis; peripheral neuropathy; bladder cancer; docetaxel; febrile neutropenia; fever; nail disease; pneumonia; pruritus; rash; hyperkalemia; hyponatremia; malaise; heart failure; peripheral edema; interstitial lung disease; phase 3 clinical trial; leukocyte count; hyperthyroidism; hypothyroidism; corticosteroid; insulin dependent diabetes mellitus; hiccup; alopecia; transitional cell carcinoma; japanese; lymphocyte count; vinflunine; dysgeusia; nail discoloration; decreased appetite; corticosteroid therapy; immune checkpoint blockade; upper abdominal pain; advanced urothelial cancer; immune mediated injury; objective response rate; human; male; female; priority journal; article; pembrolizumab; japanese (people); keynote-045 |
| Journal Title: | International Journal of Clinical Oncology |
| Volume: | 25 |
| Issue: | 1 |
| ISSN: | 1341-9625 |
| Publisher: | Springer Japan KK |
| Date Published: | 2020-01-01 |
| Start Page: | 165 |
| End Page: | 174 |
| Language: | English |
| DOI: | 10.1007/s10147-019-01545-4 |
| PUBMED: | 31729625 |
| PROVIDER: | scopus |
| PMCID: | PMC6946746 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2020 -- Source: Scopus |
