Pembrolizumab Gets New Indications in Advanced Cancer

Article

The FDA has granted approval to pembrolizumab (Keytruda) in the first- and second-line settings for the treatment of patients with locally advanced or metastatic urothelial carcinoma.

Pembrolizumab was approved in the first- and second-line settings

The US Food and Drug Administration (FDA) has granted pembrolizumab (Keytruda) regular approval for the second-line treatment of locally advanced or metastatic urothelial carcinoma patients whose disease has progressed during or after platinum-containing chemotherapy, either in the neoadjuvant or adjuvant setting, as well as accelerated approval for the first-line treatment of cisplatin-ineligible patients.

“Keytruda is now available for use as a first-line treatment option for patients with advanced urothelial bladder cancer who are not eligible for the standard of care, cisplatin-based chemotherapy,” said study investigator Dean F. Bajorin, MD, medical oncologist at Memorial Sloan Kettering Cancer Center in New York, in a press release. “With the second-line indication, Keytruda also provides a new option for patients with advanced urothelial bladder cancer-and is the only anti–PD-1 therapy to show an overall survival benefit vs chemotherapy in a phase III study.”

Results from the multicenter KEYNOTE-045 trial led to the pembrolizumab approval in the second-line setting. The trial randomized 542 patients with locally advanced or metastatic urothelial carcinoma, whose disease had progressed on or after platinum-containing chemotherapy, to either pembrolizumab or chemotherapy. Every 3 weeks, patients received either 200-mg pembrolizumab (n = 270) or investigator’s choice of chemotherapy (n = 272; 75-mg/m2 docetaxel, 175-mg/m2 paclitaxel, or 320-mg/m2 vinflunine).

Patients on pembrolizumab had an improved overall response rate (21% vs 11%; P = .002). Median overall survival was also improved with pembrolizumab, at 10.3 months vs 7.4 months in those on chemotherapy for a hazard ratio (HR) of 0.73 (95% CI, 0.59–0.91; P = .004).

Results from the KEYNOTE-052 trial led to the pembrolizumab approval in the first-line setting. This open-label trial included 370 cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. Pembrolizumab was administered every 3 weeks at a 200-mg dose in all patients. Overall response rate was 28.6% (95% CI, 24%–34%) with a median follow-up of 7.8 months; the median response duration was not reached (1.4–17.8 months).

Adverse events (AEs) led to treatment discontinuation in 8% of patients In KEYNOTE-045 and 11% of patients in KEYNOTE-052, with pneumonitis (1.9%) being the most common reason. AEs led to treatment interruption in 20% of patients, with diarrhea and urinary tract infection (1.5% each) and colitis (1.1%) being the most common reasons.

The most common AEs (20% or greater) in pembrolizumab-treated vs chemotherapy-treated patients were decreased appetite (21% vs 21%), fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), nausea (21% vs 29%), pruritus (23% vs 6%), and rash (20% vs 13%). Serious AEs occurred in 39% of pembrolizumab-treated patients, with anemia, pneumonia, pneumonitis, and urinary tract infection being the most common (all 2% or greater).

Newsletter

Stay up to date on recent advances in the multidisciplinary approach to cancer.

Recent Videos
Various methods of communication ensure that members from radiation oncology, pathology, and other departments are on the same page regarding treatment.
Comprehensive prehabilitation may help prepare patients for bladder-preserving surgery, helping to optimize quality of life outcomes.
Ongoing research suggests environmental exposures and the role of microbiomes may influence bladder cancer development and response to treatment.
Related Content