"While we are disappointed in these study results, Keytruda has been established as an important option in the treatment of metastatic bladder cancer, and we are committed to continuing our research to help more patients with this disease."
Frontline treatment with pembrolizumab (Keytruda) in combination with chemotherapy failed to demonstrate a significant improvement in survival over chemotherapy alone in patients with advanced or metastatic urothelial carcinoma in the final analysis of the phase 3 KEYNOTE-361 trial.
A clinical benefit was seen in terms of progression-free survival (PFS) and overall survival (OS) with the combination, but this did not reach statistical significance. Thus, the pre-specified dual primary end points were not met in the study.
“In this study, Keytruda in combination with chemotherapy in previously untreated patients with advanced or metastatic bladder cancer was rigorously tested against an active control of the current standard of care chemotherapy combination regimen,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said in a statement. “While we are disappointed in these study results, Keytruda has been established as an important option in the treatment of metastatic bladder cancer, and we are committed to continuing our research to help more patients with this disease."
As the combination arm did not demonstrate superiority, the pembrolizumab monotherapy arm was not formally tested.
The trial did show a consistent safety profile for pembrolizumab and chemotherapy compared with prior reports and no new safety signals were identified.
Further findings from the trial will be presented at an upcoming medical meeting and discussed with regulatory authorities.
The KEYNOTE-361 trial was a randomized, open-label study explored the use of pembrolizumab and chemotherapy or pembrolizumab alone in comparison with standard-of-care chemotherapy as a first-line treatment of patients with advanced or metastatic urothelial carcinoma (NCT02853305).
A total of 1010 patients were randomized to one of 3 treatment arms. Participants were those who had histologically or cytologically confirmed advanced/unresectable or metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra. Eligible patients had not received any prior systemic therapy for advanced or metastatic disease with the exception of neoadjuvant platinum-based chemotherapy with a recurrence more than 12 months after completing therapy and adjuvant platinum-based chemotherapy after radical cystectomy and a recurrence more than a year after completing treatment. All patients had to have an ECOG performance status of 0 to 2 and adequate organ function.
In the combination arm patients received 200 mg intravenous (IV) pembrolizumab on day 1 of every 3-week cycle for up to 35 cycles, plus IV cisplatin at 70 mg/m2 or IV carboplatin at area under the curve (AUC) 5 or 4.5 on day 1 or 2 of each cycle, and 1000 mg/m2 of IV gemcitabine on days 1 and 8 of each cycle.
The primary end points were PFS by RECIST 1.1 criteria as assessed by independent central review and OS. Secondary end points included adverse events, objective response rate, disease control rate, duration of response, and health-related quality-of-life scores.
Pembrolizumab is FDA-approved for 3 bladder cancer indications: for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy and whose tumors express PD-L1, defined as a combined positive score ≥10 determined by an FDA-approved test, or in patients who are not eligible for platinum-containing chemotherapy regardless of PD-L1 status; as treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or
after platinum-containing chemotherapy, or within 12 months of receiving neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and as treatment for patients with Bacillus Calmette-Guerin (BCG)–unresponsive, high-risk, non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are not eligible for or have elected not to undergo cystectomy. The anti–PD-1 therapy is also approved for the treatment of many solid tumors, hematologic malignancies, and tumor-agnostic indications.
The PD-1 inhibitor is undergoing further study as monotherapy and in combination regimens across several bladder cancer disease settings.
Merck Provides Update on Phase 3 KEYNOTE-361 Trial Evaluating KEYTRUDA® (pembrolizumab) as Monotherapy and in Combination with Chemotherapy in Patients with Advanced or Metastatic Urothelial Carcinoma. News release. Merck. June 9, 2020. Accessed June 10, 2020. https://bwnews.pr/3hcmwCM