Efficacy and toxicity of immune checkpoint inhibitors combination therapy for advanced renal cell carcinoma: a systematic review and network meta-analysis.
Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection.
We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results.
An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs).
Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern.
https://inplasy.com/, identifier INPLASY202410078.
Chen X
，Xu Z
，Wu C
，Xie L
，Wang P
，Liu X
... -
《Frontiers in Immunology》
Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial.
Systemic therapies have improved the management of hepatocellular carcinoma, but there is still a need to further enhance overall survival in first-line advanced stages. This study aimed to evaluate the addition of pembrolizumab to lenvatinib versus lenvatinib plus placebo in the first-line setting for unresectable hepatocellular carcinoma.
In this global, randomised, double-blind, phase 3 study (LEAP-002), patients aged 18 years or older with unresectable hepatocellular carcinoma, Child Pugh class A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous systemic treatment were enrolled at 172 global sites. Patients were randomly assigned (1:1) with a central interactive voice-response system (block size of 4) to receive lenvatinib (bodyweight <60 kg, 8 mg/day; bodyweight ≥60 kg, 12 mg/day) plus pembrolizumab (200 mg every 3 weeks) or lenvatinib plus placebo. Randomisation was stratified by geographical region, macrovascular portal vein invasion or extrahepatic spread or both, α-fetoprotein concentration, and Eastern Cooperative Oncology Group performance status. Dual primary endpoints were overall survival (superiority threshold at final overall survival analysis, one-sided p=0·019; final analysis to occur after 532 events) and progression-free survival (superiority threshold one-sided p=0·002; final analysis to occur after 571 events) in the intention-to-treat population. Results from the final analysis are reported. This study is registered with ClinicalTrials.gov, NCT03713593, and is active but not recruiting.
Between Jan 17, 2019, and April 28, 2020, of 1309 patients assessed, 794 were randomly assigned to lenvatinib plus pembrolizumab (n=395) or lenvatinib plus placebo (n=399). Median age was 66·0 years (IQR 57·0-72·0), 644 (81%) of 794 were male, 150 (19%) were female, 345 (43%) were Asian, 345 (43%) were White, 22 (3%) were multiple races, 21 (3%) were American Indian or Alaska Native, 21 (3%) were Native Hawaiian or other Pacific Islander, 13 (2%) were Black or African American, and 46 (6%) did not have available race data. Median follow up as of data cutoff for the final analysis (June 21, 2022) was 32·1 months (IQR 29·4-35·3). Median overall survival was 21·2 months (95% CI 19·0-23·6; 252 [64%] of 395 died) with lenvatinib plus pembrolizumab versus 19·0 months (17·2-21·7; 282 [71%] of 399 died) with lenvatinib plus placebo (hazard ratio [HR] 0·84; 95% CI 0·71-1·00; stratified log-rank p=0·023). As of data cutoff for the progression-free survival final analysis (April 5, 2021), median progression-free survival was 8·2 months (95% CI 6·4-8·4; 270 events occurred [42 deaths; 228 progressions]) with lenvatinib plus pembrolizumab versus 8·0 months (6·3-8·2; 301 events occurred [36 deaths; 265 progressions]) with lenvatinib plus placebo (HR 0·87; 95% CI 0·73-1·02; stratified log-rank p=0·047). The most common treatment-related grade 3-4 adverse events were hypertension (69 [17%] of 395 patients in the lenvatinib plus pembrolizumab group vs 68 [17%] of 395 patients) in the lenvatinib plus placebo group), increased aspartate aminotransferase (27 [7%] vs 17 [4%]), and diarrhoea (25 [6%] vs 15 [4%]). Treatment-related deaths occurred in four (1%) patients in the lenvatinib plus pembrolizumab group (due to gastrointestinal haemorrhage and hepatorenal syndrome [n=1 each] and hepatic encephalopathy [n=2]) and in three (1%) patients in the lenvatinib plus placebo group (due to gastrointestinal haemorrhage, hepatorenal syndrome, and cerebrovascular accident [n=1 each]).
In earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo. Our findings do not support a change in clinical practice.
Eisai US, and Merck Sharp & Dohme, a subsidiary of Merck.
Llovet JM
，Kudo M
，Merle P
，Meyer T
，Qin S
，Ikeda M
，Xu R
，Edeline J
，Ryoo BY
，Ren Z
，Masi G
，Kwiatkowski M
，Lim HY
，Kim JH
，Breder V
，Kumada H
，Cheng AL
，Galle PR
，Kaneko S
，Wang A
，Mody K
，Dutcus C
，Dubrovsky L
，Siegel AB
，Finn RS
，LEAP-002 Investigators
... -
《-》
French AFU Cancer Committee Guidelines - Update 2024-2026: Management of kidney cancer.
To update the French recommendations for the management of kidney cancer.
A systematic review of the literature was conducted for the period from 2014 to 2024. The most relevant articles concerning the diagnosis, classification, surgical treatment, medical treatment, and follow-up of kidney cancer were selected and incorporated into the recommendations. The recommendations have been updated specifying the level of evidence (strong or weak).
Kidney cancer following prolonged occupational exposure to trichloroethylene should be considered an occupational disease. The reference examination for the diagnosis and staging of kidney cancer is the contrast-enhanced thoraco-abdominal CT scan. PET scans are not indicated in the staging of kidney cancer. Percutaneous biopsy is recommended in situations where its results will influence therapeutic decisions. It should be used to reduce the number of surgeries for benign tumors, particularly avoiding unnecessary radical nephrectomies. Kidney tumors should be classified according to the pTNM 2017 classification, the WHO 2022 classification, and the ISUP nucleolar grade. Metastatic kidney cancers should be classified according to IMDC criteria. Surveillance of tumors smaller than 2cm should be prioritized and can be offered regardless of patient age. Robot-assisted laparoscopic partial nephrectomy is the reference surgical treatment for T1 tumors. Ablative therapies and surveillance are options for elderly patients with comorbidities for tumors larger than 2cm. Stereotactic radiotherapy is an option to discuss for treating localized kidney tumors in patients not eligible for other treatments. Radical nephrectomy is the first-line treatment for locally advanced localized cancers. Pembrolizumab is recommended for patients at high risk of recurrence after surgery for localized kidney cancer. In metastatic patients, cytoreductive nephrectomy can be immediate in cases of good prognosis, delayed in cases of intermediate or poor prognosis for patients stabilized by medical treatment, or as "consolidation" in patients with complete or major partial response at metastatic sites after systemic treatment. Surgical or local treatment of metastases can be proposed for single lesions or oligometastases. Recommended first-line drugs for metastatic clear cell renal carcinoma are combinations of axitinib/pembrolizumab, nivolumab/ipilimumab, nivolumab/cabozantinib, and lenvatinib/pembrolizumab. Patients with non-clear cell metastatic kidney cancer should be presented to the CARARE Network and prioritized for inclusion in clinical trials.
These updated recommendations are a reference that will enable French and French-speaking practitioners to optimize their management of kidney cancer.
Bigot P
，Boissier R
，Khene ZE
，Albigès L
，Bernhard JC
，Correas JM
，De Vergie S
，Doumerc N
，Ferragu M
，Ingels A
，Margue G
，Ouzaïd I
，Pettenati C
，Rioux-Leclercq N
，Sargos P
，Waeckel T
，Barthelemy P
，Rouprêt M
... -
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ResearchGate
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钛学术
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