2024-01-30 02:32:00
Kidney cancer, immunotherapy after surgery increases survival
Il Keynote-564 it is the first phase 3 study that has demonstrated increased overall survival with the use of adjuvant therapy compared to placebo in patients suffering from carcinoma to renal cells (Rcc) .
Roberto Iacovelliassociate professor of medical oncology, Catholic University of the Sacred Heart, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli Irccs of Rome: “The Keynote-564 represents a milestone in oncology. It is the first study to have demonstrated how immunotherapy with pembrolizumab can not only cure but also help cure kidney cancer”
The latest overall survival results have been selected for the official press program of the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.
Immunotherapy in the adjuvant phase, i.e. administered after surgery, reduced the risk of death by 38% significantly improving survival. The results demonstrate this Phase 3 study in which pembrolizumab, MSD’s anti-PD-1 therapy, was used as adjuvant therapy in patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or after nephrectomy and resection of lesions metastatic.
This late-breaking data was first presented in an oral session during theAmerican Society of Clinical Oncology (Asco) Genitourinary (GU) Cancers Symposium 2024 (abstract #LBA359), which took place recently, and included in the official media program of Asco Gu.
At the third predefined interim analysis (median follow-up of 57.2 months [intervallo, 47,9−74,5 mesi]), pembrolizumab as adjuvant therapy significantly improved overall survival (OS) by 38% compared to placebo.
At 48 months, the estimated rate of Os was 91.2% in patients treated with pembrolizumab compared to 86% in patients treated with placebo. OS benefit in patients treated with pembrolizumab was observed in major subgroups. Overall survival was the primary secondary endpoint of the study.
“In Italy, in 2023, approximately 12,700 new diagnoses of kidney cancer were estimated, 85% of which with localized disease. Among these, about half can be considered a intermediate-high risk of developing metastases within a few years of diagnosis, leading to a marked worsening of life expectancy despite the recent progress made in the treatment of advanced forms – he states Roberto Iacovelli-. These patients are the same ones who were enrolled in the Keynote-564 study, the first and only clinical study in the history of renal cell carcinoma treatment to have demonstrated how immunotherapy after nephrectomy reduces the risk of developing metastases thus prolonging survival. All this translates concretely into the possibility of curing patients, ensuring them a life free from cancer. The Keynote-564 study therefore represents a milestone in oncology, being the first study to have demonstrated how immunotherapy with pembrolizumab can not only cure but also help heal kidney cancer”.
“The positive overall survival results for Keynote-564 complement the progression-free survival data that supported the approval of pembrolizumab for this indication worldwide,” he says Marjorie Green, senior vice president and director of oncology, global clinical development, Merck Research Laboratories. “This is the second study of pembrolizumab to demonstrate a significant overall survival benefit at an early stage of the disease, and these new results add to the progress we are making in the early stages of the disease.”
As reported at a previous pre-specified interim analysis at a median follow-up of 24.1 months, the Keynote-564 study met its primary endpoint of disease-free survival (DFS), reducing the risk of relapse or death by 32%. compared to placebo. At the third interim analysis, the benefit of Dfs was consistent with previously reported data for patients treated adjuvantly with pembrolizumab versus placebo.
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Pembrolizumab is approved as adjuvant therapy for patients with RCC in United States, European Union, Japan and in others Countries of the world based on Dfs data from the Keynote-564 study, which was presented for the first time at the Asco Annual Meeting 2021. MSD is currently working with health authorities to include Os data in pembrolizumab prescribing information.
MSD has a vast clinical development program in renal cell carcinoma in multiple settings, both in adjuvant and for advanced disease, using pembrolizumab as monotherapy or in combination with belzutifan (oral inhibitor of hypoxia-inducible factor 2-alpha [HIF-2α] of MSD), lenvatinib (a multi-target kirosine kinase inhibitor that inhibits VEGF activity, in collaboration with Eisai) and quavonlimab (an anti-CTLA-4 monoclonal antibody under development through an agreement with Akeso Inc.).
Design and additional data from the KEYNOTE-564 study
Keynote-564 is a randomized, double-blind, Phase 3 study (ClinicalTrials.gov, NCT03142334) evaluating pembrolizumab for the adjuvant treatment of RCC patients with high-intermediate, high-risk, and M1-risk disease without evidence of disease (NED) undergoing nephrectomy. L’endpoint primario is Dfs, assessed by the investigator and secondary endpoints include OS and safety profile. The study enrolled 994 patients randomized 1:1 receive pembrolizumab (200 mg intravenously [IV] on day 1 of each three-week cycle for up to 17 cycles) or placebo (IV saline on day 1 of each three-week cycle for up to 17 cycles).
The OS benefit for patients treated with pembrolizumab was observed in key subgroups, including patients with M0 disease (HR=0.63 [95% CI, 0,44-0,90]), M1 NED (HR=0,51 [95% CI, 0,15-1,75]), PD-L1 combined positive score (CPS) <1 (HR=0.65 [95% CI, 0,31−1,38]) o CPS ≥1 (HR=0,62 [95% CI, 0,42−0,91]), and patients with presence (HR=0.69 [95% CI, 0,28−1,70]) or absence (HR=0.57 [95% CI 0,39−0,84]) of sarcomatoid characteristics. However, the study was not designed to detect statistical differences between subgroups.
The safety profile of pembrolizumab was consistent with that observed in previous studies; no new safety signals were observed. Treatment-related adverse events (TRAEs) occurred in 79.1% of patients (n=386) in the pembrolizumab arm and 53.0% (n=263) of those in the placebo arm. THE Grade 3-4 Traes were observed in 18.6% of patients in the pembrolizumab arm and 1.2% of those in the placebo arm.
Treatment-related adverse events resulting in discontinuation of any therapy occurred in 18.2% of patients in the pembrolizumab arm and 0.8% of patients in the placebo arm. No deaths occurred due to treatment.
Renal cell carcinoma is the most common type of kidney tumor; Approximately 9 out of 10 kidney cancer diagnoses consist of renal cell carcinoma. RCC is twice as common in men as women. Most renal cell carcinomas are diagnosed incidentally during diagnostic tests for other abdominal disorders. Rcc is associated with a high risk of recurrence, with approximately 40% of newly diagnosed patients having develops recurrence five years after surgery.
In the United States, approximately 81,600 new cases of kidney cancer diagnosis and approximately 14,400 deaths from this disease are estimated in 2024. TO world level, it is estimated that in 2020 there were approximately 431,000 new diagnoses of kidney cancer and more than 179,000 deaths from this disease. In Italy, in 2023, approximately 12,700 new diagnoses were estimated with 4,600 deaths reported in 2022. Finally, there are 144,400 patients alive in our country following a diagnosis of kidney cancer.
Diagnosing cancer at an early stage can offer patients greater long-term survival. Many tumors are considered more treatable and potentially curable in the early stages of the disease. Based on its deep understanding of the role of pembrolizumab in advanced cancers, MSD is also evaluating pembrolizumab in the early stages of the disease, with more than 25 pivotal studies underway in different tumor types.
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