NEW YORK (Reuters Health) – The combination of the multikinase inhibitor lenvatinib and the anti-PD-1 antibody pembrolizumab has “encouraging” antitumor activity and a manageable side effect profile and might be an option following immune-checkpoint inhibitor (ICI) therapy in patients with metastatic renal-cell carcinoma (RCC), researchers report.
Despite advances in the first-line treatment of metastatic RCC, there is “an unmet need” for options to address disease progression during or after treatment ICI therapy, Dr. Chung-Han Lee of Memorial Sloan Kettering Cancer Center, in New York City, and colleagues writes in The Lancet Oncology.
Pembrolizumab and lenvatinib are active as monotherapies in RCC. The phase-1b/2 Study 111/KEYNOTE-146 trialists tested the combination in 145 patients with metastatic RCC. Two patients with non-clear-cell RCC were excluded from the efficacy analysis but included in the safety analysis.
The efficacy population included 22 treatment-naive patients, 17 patients previously treated with at least one line of therapy but not with an anti-PD-1 or anti-PD-L1 ICI, and 104 ICI-pretreated patients (prior anti-PD-1 or anti-PD-L1 therapy).
The regimen consisted of oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg once every three weeks. Patients remained on treatment until their disease progressed, they developed unacceptable toxicity, or they withdrew consent. The median follow-up was 19.8 months.
“The objective response rate at week 24 by investigator assessment per irRECIST was high in all three groups of patients,” the researchers report.
Sixteen of 22 (73%) treatment-naive patients had an objective response at week 24, as did was seven of 17 (41%) of previously treated ICI-naive patients, and 58 of 104 (56%) of ICI-pretreated patients.
Of 145 patients, 82 (57%) had grade-3 treatment-related adverse events and 10 (7%) had grade-4 treatment-related adverse events.
Hypertension was the most common grade-3 treatment-related adverse event occurring in 30 patients (21%). Treatment-related serious adverse events occurred in 36 (25%) patients, and there were three treatment-related deaths (upper gastrointestinal hemorrhage, sudden death, and pneumonia).
“To our knowledge, this is the largest study to date with a TKI plus ICI in the metastatic renal cell carcinoma therapeutic setting after disease progression with previous ICI (ie, anti-PD-1 or anti-PD-L1) therapy. Notably, the safety profile of the combination was consistent with the safety profiles of each agent,” the study team writes.
Lenvatinib plus pembrolizumab might be a “future potential standard-of-care treatment for patients with metastatic clear cell RCC after disease progression with ICI therapy,” they say.
“This combination is being further investigated in phase 3 trials involving patients with various tumor types, including a study in advanced or metastatic renal cell carcinoma,” the study team says.
The study was funded by Eisai and Merck Sharp and Dohme. Several authors have disclosed financial relationships with the companies.
SOURCE: https://bit.ly/3qsvAbx The Lancet Oncology, online June 15, 2021.
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