Renal cell carcinoma (RCC) is a malignant tumor that originates in the kidney, and can be divided into clear cell type and non-clear cell type according to the morphological characteristics of tumor cells. Non-clear cell renal cell carcinoma (NCCRCC) accounts for 15% to 20% of RCC and includes papillary, chromosomal, unclassified, translocated, and other subtypes. The prognosis of non-clear cell renal cell carcinoma is poor, there is currently no clear first-line standard, and there is a lack of effective targeted drugs and immunity.
Recently, at the 2024 Genitourinary Oncology Symposium, Martin H. from Memorial Sloan Kettering Cancer CenterDr. Voss et al. report updated results from a single-arm, multicenter, Phase II clinical trial (KEYNOTE-B61) evaluating the safety and efficacy of pembrolizumab and lenvatinib in the first-line combination** of advanced non-clear cell renal cell carcinoma.
Pembrolizumab is an anti-PD-1 monoclonal antibody that activates the immune system's tumor-killing effect by blocking the PD-1 PD-L1 signaling pathway between tumor cells and immune cells. Lenvatinib is a multi-targeted tyrosine kinase inhibitor that simultaneously inhibits multiple signaling pathways associated with tumor angiogenesis, proliferation, and invasion, including VEGF receptor, FGF receptor, PDGF receptor, RET, and KIT. The combination of the two drugs may produce synergistic or additive anti-tumor effects.
The Keynote-B61 trial included a total of 158 patients with advanced non-clear cell renal cell carcinoma who had not received systemic **, of which the papillary subtype accounted for 589%, chromosomal subtypes account for 184%, and unclassified subtypes accounted for 127%, and the translocation subtype accounted for 38% and other subtypes account for 63%。Patients receive 400 mg of pembrolizumab intravenously and 20 mg of lenvatinib orally daily every 6 weeks until disease progression, unacceptable toxicity***, or other reasons for termination**. The primary endpoint is objective response rate (ORR), and secondary endpoints include disease control rate (DCR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Data analysis up to July 5, 2023 showed a median follow-up time of 22At 8 months, the ORR was 50 for patients in the whole group6%, of which the complete response (CR) rate is 82% with a partial response (PR) rate of 424% with a DCR of 823% and 71 CBR5% with a median DOR of 195 months. By subtype, the ORR of the papillary subtype was 538%, chromosomal subtype 345%, 50 for unclassified subtypes0%, translocation subtype 667% and 60 for other subtypes0%。The median PFS for patients in the whole group was 17At 9 months, median OS has not been reached. The PFS rate at 12 and 18 months was 63., respectively9% and 481%, and the OS rate is 81., respectively6% and 725%。PFS and OS for papillary and chromosomal subtypes also showed good persistence.
In terms of security, 99At least one adverse event (AE) occurred in 4% of patients, 70Grade 3 to 5 AEs were present in 9% of patients,266% of patients discontinued any** due to AE. The most common** associated AEs (TRAEs) include hypertension, diarrhea, hypothyroidism, proteinuria, fatigue, hand-foot syndrome, hoarseness, loss of appetite, nausea, weight loss, and more. 58.Immune-related AEs were present in 2% of patients, of whom 95% for grades 3-5, 13Corticosteroids are required in 9% of patients**.
The researchers concluded that the latest results of pembrolizumab and lenvatinib in combination with ** advanced non-clear cell renal cell carcinoma continue to show good anti-tumor activity and durable survival benefits, with a clear advantage over historical controls. The safety profile of this regimen is also acceptable, consistent with previous reports. These results provide a new first-line** option for patients with non-clear cell renal cell carcinoma and lay the groundwork for future Phase III clinical trials.
References: 1, Voss MH, Gurney H, Atduev V, et al first-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccrcc): extended follow-up of the phase 2 keynote-b61 study. j clin oncol. 2024;42(suppl; abstr 2).
2,motzer r, alekseev b, rha s-y, et al. lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. n engl j med. 2021;384(14):1289-1300.
3,albiges l, gurney h, atduev 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.