As the first study of its kind, KEYNOTE-B61 has demonstrated potential to move pembrolizumab plus lenvatinib earlier in the treatment of non-clear cell renal cell carcinoma.
Pembrolizumab (Keytruda) given in combination with lenvatinib (Lenvima) has demonstrated durable antitumor efficacy in patients with non-clear cell renal cell carcinoma (nccRCC), and showed a safety profile consistent with prior studies, according to findings from the KEYNOTE-B61 study (NCT04704219).1
The findings, which were published in The Lancet Oncology, were from 158 patients enrolled at 48 different locations across 14 countries, including the United States. According to the study authors led by Laurence Albiges, MD, PhD, a medical oncologist at Institut Gustave Roussy, these finding support additional research around this combination in nccRCC.
“Our results support the use of pembrolizumab plus lenvatinib as a first-line therapeutic option for advanced non-clear cell renal cell carcinoma, regardless of histology. Further randomized controlled trials are needed to better elucidate the role of checkpoint inhibitor combinations in this setting,” wrote Albiges et al, in The Lancet Oncology.
A confirmed objective response rate of 49% (95% CI, 41%-57%) was shown with pembrolizumab/lenvatinib. Responses included confirmed complete responses in 44% of patients, confirmed partial response in 43%, stable disease in 33%, and progressive disease in 11%. The clinical benefit rate was 72% (95% CI, 64-78). Moreover, there was a 30% tumor size reduction in 58% of patients.
Responses were also evaluated in various histology groups, and results showed that response rates were similar in patients whose histology was determined by central pathology. Good responses were especially achieved in the papillary and chromophobe histology subgroups.
The median progression-free survival (PFS) was 18 months (95% CI, 14 months to not reached) with pembrolizumab and lenvatinib with a 63% (95% CI 54%-70%) estimated 12-month PFS rate. The median overall survival was not reached, but as of the data cutoff point, 22% of patients have died.
Treatment lasted for a median duration of 9.7 months (interquartile range, 4.2-14.0 months).Safety findings showed that any-grade treatment-related adverse events (TRAEs) occurred in 945% of patients. The most common TRAEs observed with pembrolizumab/lenvatinib were hypertension (57%), diarrhea (44%), and hypothyroidism (37%). The most common grade 3 or 4 TRAEs included hypertension (23%), proteinuria (4%), and stomatitis (4%).
Serious TRAEs occurred in 20% if patients. More commonly than not, these serious TRAEs involved acute kidney injury, increased aspartate aminotransferase, asthenia, diarrhea, and hyponatremia. There were 8 deaths in the study related with AEs, but none were treatment-related. AEs leading to death were cardiac failure, peritonitis, pneumonia, sepsis, cerebrovascular accident, suicide, pneumothorax, and pulmonary embolism, which occurred in 1 patient each.
Dose reduction required because of AEs were provided for 34% of patients. AEs leading to dose interruption or discontinuation of treatment occurred in 72% and 20% of patients, respectively.
The most common AEs of clinical interested were hypertension (61%), hypothyroidism (42%), proteinuria (31%), and palmar-plantar erythrodysesthesia syndrome (30%). Immune-related AEs were observed in 53% of patients, of which the most common were hypothyroidism (42%), hyperthyroidism (12%), adrenal insufficiency (4%), and pneumonitis (3%), hypothyroidism (42%), hyperthyroidism (12%), adrenal insufficiency (4%), and pneumonitis (3%).
“To our knowledge, KEYNOTE-B61 is the largest prospective clinical trial to date to investigate a combination therapy based on an immune checkpoint inhibitor for the first-line treatment of non-clear-cell renal cell carcinoma. Anti-tumor activity was also consistently observed across subgroups, including by histological subtype, International Metastatic Renal Cell Carcinoma Database Consortium risk category, and the presence or absence of sarcomatoid features,” wrote Albiges et al. “The safety profile of pembrolizumab plus lenvatinib was similar to that observed previously, with no new safety signals reported,” the authors added.
Albiges L, Gurnery H, Atdeuv V, et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2023;24(8): 881-891. doi:10.1016/S1470-2045(23)00276-0