Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Advanced Melanoma
In the phase IB KEYNOTE-029 study, standard-dose pembrolizumab (Keytruda) plus reduced-dose ipilimumab (Yervoy) produced high response rates in patients with advanced melanoma. These results were reported by Long et al in The Lancet Oncology.
Study Details
In the study, 153 patients with unresectable stage III or IV melanoma who had received no prior immune checkpoint inhibitor treatment and had no active brain metastases received pembrolizumab at 2 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses followed by pembrolizumab at 2 mg/kg every 3 weeks for up to 2 years. Overall, 83% of patients were programmed cell death ligand 1 (PD-L1)–positive.
Response Rates
As of the data cutoff in October 2016, median follow-up was 17.0 months. The objective response rate was 61% (95% confidence interval = 53%–69%), including 62% in PD-L1–positive patients and 50% in PD-L1–negative patients. Median duration of response was not reached. Estimated 1-year progression-free survival was 69%, and estimated 1-year overall survival was 89%.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 45% of patients, with the most common being elevated lipase (16%) and autoimmune hepatitis (6%). Treatment-related adverse events led to discontinuation of pembrolizumab and ipilimumab in 14% of patients, pembrolizumab only in 9%, and ipilimumab only in 8%. No treatment-related deaths occurred. Immune-mediated adverse events of any grade occurred in 60% and were grade 3 or 4 in 27%. The most common were hypothyroidism (16%) and hyperthyroidism (11%).
The investigators concluded: “Standard-dose pembrolizumab given in combination with four doses of reduced-dose ipilimumab followed by standard-dose pembrolizumab has a manageable toxicity profile and provides robust anti-tumour activity in patients with advanced melanoma. These data suggest that standard-dose pembrolizumab plus reduced-dose ipilimumab might be a tolerable, efficacious treatment option for patients with advanced melanoma. A randomised phase 2 trial of alternative dosing strategies of this combination is underway.”
The study was funded by Merck & Co, Inc.
Georgina V. Long, MBBS, of Melanoma Institute Australia, University of Sydney, is the corresponding author of The Lancet Oncology article.
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