This article is more than 5 years old. Information may no longer be current.
Pembrolizumab active as first-line therapy in renal cell carcinoma subtype
Click Here to Manage Email Alerts
CHICAGO — Pembrolizumab monotherapy in the first-line setting induced a response among nearly 40% of patients with clear cell renal cell carcinoma across all IMDC risk groups, according to interim results from cohort A of the KEYNOTE-427 trial presented at the ASCO Annual Meeting.
Also, pembrolizumab (Keytruda, Merck) appeared safe and had a similar safety profile as seen with pembrolizumab in other tumor types, according to the researchers.
“While atezolizumab [Tecentriq, Genentech] monotherapy [has] displayed encouraging antitumor activity in treatment-naive patients in a randomized phase 2 study, less is known about the activity of single-agent PD-1 blockade in treatment-naive patients with clear cell renal cell carcinoma,” David F. McDermott, MD, leader of the kidney cancer program at the Dana-Farber / Harvard Cancer Center, said during his presentation. “The KEYNOTE-427 trial is the first clinical trial to explore the antitumor activity of single-agent PD-1 blockade with pembrolizumab in previously untreated patients with clear and non-clear cell kidney cancer.”
For the phase 2 cohort A of the KEYNOTE-427 trial, McDermott and colleagues evaluated the efficacy, safety and tolerability of pembrolizumab among patients with clear cell renal cell carcinoma.
In cohort A, 110 enrolled patients (median age, 64 years; 78.2% men) received 200 mg of pembrolizumab every 3 weeks.
Responses were assessed at week 12 and every 6 weeks afterward until week 54. After week 54, the researchers assessed responses every 12 weeks.
Overall response rate served as the primary endpoint.
Secondary endpoints included duration of response, progression-free and overall survival as well as safety and tolerability.
Researchers observed an overall response among 38.2% (95% CI, 29.1-47.9) of treated patients across all IDMC risk groups.
Median time to response was 2.8 months and the median duration of response was not reached.
Encouraging activity was observed in IMDC intermediate- and poor-risk (n = 69) groups with an overall response rate of 42% (95% CI, 30.2-54.5), according to McDermott.
Researchers observed a median PFS of 8.7 months (95% CI, 6.7-12.2), while a median OS was not reached.
The most common adverse events regardless of grade included pruritus, fatigue, diarrhea and rash.
Diarrhea (n = 4) and colitis (n = 3) were the most common grade 3 and grade 4 adverse events.
Hypothyroidism (10.9%), hyperthyroidism (4.5%) and pneumonitis (4.5%) were labeled adverse events of special interest.
One patient died from treatment-related pneumonitis, according to McDermott.
McDermott said that the results of KEYNOTE-427 will help researchers better understand the benefit of combination therapies.
“We think [these results] provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti–PD-1–based combination therapies in better context,” he said. – by Ryan McDonald
Reference:
McDermott DF, et al. Abstract 4500. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: McDermott reports consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer and X4 Pharma.