Updated data from the KEYNOTE-365 study reported at the ESMO Asia Virtual Congress 2020, held November 20 to 22 confirms three individual combination treatments containing pembrolizumab (Keytruda®; Merck & Co; previously known as MK-3475) provided anti-tumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC).[1]

Anthony M. Joshua, BSc (Med) (HONS) MBBS (HONS) Ph.D., (UToronto) FRACP, an associate professor at Kinghorn Cancer Centre, St Vincent’s Hospital in Sydney, NSW, Australia, presented updated findings from cohorts A, B, and C of the multicohort, open-label phase Ib/II KEYNOTE-365* (NCT02861573) study.

Three cohorts
The KEYNOTE-365 investigators assessed the safety and efficacy of pembrolizumab combination treatment in 3 cohorts of patients classified according to pretreatment. This non-randomized study administered pembrolizumab at 200 mg IV every 3 weeks to patients in 3 cohorts.

Patients pretreated with docetaxel (cohort A) received olaparib as a 400 mg capsule or 300 mg tablet twice daily (n = 84). In cohort B, in addition to pembrolizumab, docetaxel at 75 mg/m2 IV every 3 weeks plus oral prednisone at 5 mg twice daily was administered to patients pretreated with either abiraterone acetate or enzalutamide (n = 104).

In cohort C, in addition to pembrolizumab, oral enzalutamide at 160 mg/day was administered to patients pretreated with abiraterone acetate (n = 102).

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The primary endpoints were prostate-specific antigen (PSA) response rate, defined as confirmed PSA decrease ≥50%, objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR), and safety.

PSA response was observed in 9% of cohort A, 28% of cohort B, and 22% of patients in cohort C.

Anthony M. Joshua, BSc (Med) (HONS) MBBS (HONS) Ph.D., (UToronto) FRACP, an associate professor at Kinghorn Cancer Centre, St Vincent’s Hospital in Sydney, NSW, Australia, presented updated findings from cohorts A, B, and C of the multicohort, open-label phase Ib/II KEYNOTE-365* (NCT02861573) study.

Trial results
Measurable disease was observed in 48 (57%; cohort A), 52 (50%; cohort B), and 40 (39%; cohort C) patients in the total population of each cohort. In patients with measurable disease and ≥27 weeks of follow-up, the ORR was 8% (2/24) in cohort A, 18% (7/39) in cohort B, and 12% (3/25) in cohort C; the best responses were 2 partial response (PR), 7 PR, and 2 complete response plus 1 PR in cohorts A, B, and C, respectively,

Median radiographic progression-free survival (rPFS) was 4.3 months (95% confidence interval [CI] 3.4-7.7; cohort A), 8.3 months (95% CI 7.6-10.1; cohort B), and 6.1 months (95% CI 4.4-6.5; cohort C); 12-month rPFS rates were 23.3%, 24.0%, and 24.6%, respectively.

The study showed a median overall survival (OS) in the respective cohorts was 14.4 months (95% CI 8.1-18.5), 20.4 months (95% CI 16.9-not reached [NR]), and 20.4 months (95% CI 15.5-NR); 12-month OS rates in the respective cohorts were 58.2%, 75.8%, and 72.8%.

Adverse events
Grade ≥3 treatment-related adverse events (TRAEs) occurred in 35%, 40%, and 39% of patients in cohorts A, B, and C, respectively.

KEYNOTE-365 study design. © 2020 Anthony M. Joshua.

Deaths due to TRAEs occurred in 2 cohort A patients (1 myocardial infarction, 1 cause unknown), 2 in cohort B (pneumonitis), and 1 patient in cohort C (cause unknown).

Based on these findings, the investigators concluded that all three pembrolizumab combinations demonstrated anti-tumor activity in mCRPC, and also showed a tolerability profile that was consistent with the individual profiles of each agent.

They noted that phase III studies of each of these combinations are ongoing.

Note
* The KEYNOTE-365 study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Kenilworth, NJ, USA.

Clinical trials
Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) – NCT02861573

Highlights of prescription information
Pembrolizumab (Keytruda®; Merck & Co) [Prescribing Information]

Reference
[1] Joshua AM, Gurney H, Retz M, et al. Pembrolizumab (pembro) Combination Therapies in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC): Cohorts A-C of the Phase 1b/2 KEYNOTE-365 Study. ESMO Asia Virtual Congress 2020 (November 20 – 22). Annals of Oncology (2020) 31 (suppl_6): S1325-S1333. 10.1016/annonc/annonc369

Featured image: European Society for Medical Oncology (ESMO) Asia Congress 2018, held November 2018 in Singapore. Photo Courtesy: © 2018 – 2020 ESMO. Used with permission.

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