Treatment with Keytruda (pembrolizumab) provides anti-tumor activity and disease control in patients with metastatic castration-resistant prostate cancer (mCRPC), Merck’s large-scale Phase 2 study shows.
The company presented the study, “KEYNOTE-199: Pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC),” at the American Society of Clinical Oncology (ASCO) Annual Meeting, on Monday as part of the Genitourinary (Prostate) Cancer session. The meeting was held in Chicago June 1-5.
Keytruda is an anti-PD1 medication that boosts the immune system’s ability to detect and fight tumor cells. The therapy is currently indicated for the treatment of diverse cancer types, including melanoma, lung cancer, head and neck cancer, urothelial cancer, and classical Hodgkin’s lymphoma.
Although Keytruda showed preliminary anti-tumor activity in 23 mCRPC patients in the KEYNOTE-028 study (NCT02054806), its effectiveness has not been demonstrated in large-scale trials of mCRPC.
The scientists assessed treatment with Keytruda in 258 mCRPC patients refractory to the chemotherapy medication Taxotere (docetaxel) in the Phase 2 KEYNOTE-199 trial (NCT02787005).
Patients were divided in three groups, according to whether or not their tumor expressed PD-L1, the protein to which PD-1 on immune cells binds to (groups 1 and 2, with 131 and 67 patients, respectively). Group 3 patients (60 subjects) had bone-predominant disease.
All patients were graded 0-2 in the ECOG Performance Status, which means they were capable of self-care but not able to work, at minimum. They had received one or more endocrine therapies and one to two previous chemotherapies including Taxotere. Patients received 200 mg Keytruda every three weeks until disease progression or intolerable toxicity. The scientists determined response every nine weeks in year one, then every 12 weeks.
As of Oct 13, 2017, median follow-up in patients from groups 1-3 was 8.1, 7.9 and 11.8 months, respectively. All groups showed anti-tumor activity. Disease control rate — referring to the proportion of patients responding who achieved at least disease stabilization with the treatment — lasted six months or more in 11% of patients across the three groups.
In groups 1 and 2, 9% of patients had a 30% or greater reduction in target lesions, while 48% had target lesion changes between -30% (decreases) and +20% (increases). The scientists also observed that the response rate was higher in patients with somatic BRCA1/2 or ATM gene mutations (12%). Treatment-related grade 3-5 (severe to death-related) adverse event rates were 13% in group 1, 12% in group 2, and 17% in group 3.
“[Keytruda] shows antitumor activity and disease control with acceptable safety in patients with docetaxel-refractory mCRPC, regardless of PD-L1 status. These data support further evaluation of [Keytruda] in mCRPC,” the researchers wrote.
Patient enrollment for KEYNOTE-199 is still ongoing. For more information, click here.
Besides the study on prostate cancer, Merck, known as MSD outside the U.S. and Canada, presented new and long-term data for Keytruda, including both approved and investigational uses.
“With more data and longer follow-up across tumors and treatment settings, evidence continues to support the role of Keytruda as a foundational treatment for many types of cancer,” Roger M. Perlmutter, president, Merck Research Laboratories, said in a press release.
“At ASCO, we [presented] new and long-term overall survival data for Keytruda in advanced lung cancer and melanoma — as well as studies across our growing oncology portfolio in a number of new tumor types where we have adduced clinically meaningful results,” Perlmutter added.
The company also presented results of studies with Lynparza (olpararib) and selumetinib in collaboration with AstraZeneca, and of Lenvima in collaboration with Eisai. In total, Merck presented more than 140 studies about more than 25 tumor types.