Virginia Powers, Ph.D.
Ronald de Wit M.D., Ph.D.
Keytruda (pembrolizumab) produced better overall survival (OS) rates than chemotherapy for patients with recurrent, advanced urothelial carcinoma, according to a phase 3 KEYNOTE-045 study presented at the 2017 European Society of Medical Oncology (ESMO) Congress.
As of the cutoff point on May 19, 2017, median follow-up was 22.5 months in both arms. The median OS was significantly longer with Keytruda compared to chemotherapy in the overall patient population; median OS was 10.3 versus 7.4 months, respectively.
Significantly improved OS was observed regardless of the level of PD-L1 expression – a biomarker associated with better responses to Keytruda – as measured by combined positive score (CPS), with patients having CPS 10 percent or higher demonstrating a median OS of 8.9 with Keytruda versus 5.2 months with chemotherapy.
The 18-month OS rates were 33.2 percent compared to 19.7 percent with Keytruda versus chemotherapy, respectively.
Ronald de Wit M.D., Ph.D., group leader of the experimental systematic therapy of urogenital cancers program at Erasmus MC Cancer Institute, Rotterdam, Netherlands, presented mature results from the phase 3, multicenter, open label KEYNOTE-045 trial (NCT02256436
), which randomly assigned 270 patients with recurrent, advanced urothelial carcinoma to Keytruda at 200 mg every three weeks and 272 patients to investigators’ choice of chemotherapy (paclitaxel [Abraxane], docetaxel [Taxotere], or vinflunine [Javlor]).
Importantly, OS was longer with Keytruda versus chemotherapy regardless of age, liver metastases, hemoglobin levels, the presence of visceral disease and the choice of chemotherapy.
“Pembrolizumab is the first agent to improve survival over chemotherapy in the second-line setting. Not all patients benefit from checkpoint inhibition, but a sizeable proportion of patients who respond have very durable responses, even well over one year,” noted de Wit. “These resulting are striking in the setting of urothelial cancer, which is highly lethal in the metastatic state.”
Similar progression-free survival (PFS) was observed between the treatments; median PFS was 2.1 versus 3.3 months with Keytruda versus chemotherapy, respectively.
The objective response rate (ORR) was nearly doubled with Keytruda; ORR was 21.1 percent with Keytruda versus 11.0 percent with chemotherapy. The responses with Keytruda were more durable than with chemotherapy; the median response duration of response was not reached in the Keytruda arm versus 4.4 months.
Furthermore, no new safety signals for Keytruda were raised, which had a superior long-term safety profile versus chemotherapy.
“Treatment-related adverse events [TRAEs] of any grade occurred in 62 percent of pembrolizumab-treated patients compared to 90.6 percent of those treated with chemotherapy,” noted de Wit. The incidence of grade 3 or higher TRAEs was 16.5 percent versus 50.2 percent, respectively. Immune-related AEs occurred in 19.5 percent of patients on Keytruda compared to 7.5 percent of patients on chemotherapy. Discontinuation due to an AE occurred in 7.1 percent versus 12.5 percent of Keytruda versus chemotherapy patients, respectively.
“The US Food and Drug Administration [FDA] approved pembrolizumab in May 2017 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy,” noted de Wit. “Also, in July 2017, the FDA granted an accelerated approval to frontline pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.”
The KEYNOTE-45 trial was sponsored by Merck & Co, based in Kenilworth, New Jersey.