Dataset Information

Efficacy and safety of anti-vascular endothelial growth factor therapies in older patients for first line treatment of metastatic renal cell carcinoma.

ABSTRACT:

Background

immunotherapy became the first line treatment of metastatic renal cell carcinoma (mRCC). Nevertheless, a better understanding of the specificities of targeted therapies (TT) in the elderly population could be helpful in order to improve the management of mRCC in this population. The aim of this retrospective study was to assess efficacy and safety of sunitinib and sorafenib used as first-line TT in 70 years older patients compared to younger patients.

Methods

Data were retrospectively collected for all consecutive mRCC patients receiving first line TT treatment by sunitinib or sorafenib for mRCC from January 2006 to November 2017. Patients were divided into two groups according to the age using a cut-off at 70 years old. Median progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared using log-rank test.

Results

In total, 147 patients were included; 94 (63.9%) were <70 and 53 (36.1%) were 70 years old or more. First line TT used was sunitinib in 123 (83.7%) patients or sorafenib in 24 (16.3%) patients. Median PFS was 8 months for elderly patients vs. 6 in younger group (P=0.68). Median OS were 26 vs. 36 months (P=0.08). Severe induced toxicity was more frequent among elderly patients: 34 (64.2%) vs. 46 patients (48.9%) (P=0.07). Rate of treatment discontinuation due to toxicity was 22 patients (23.4%) in younger group vs. 28 patients (52.8%) in the elderly group (P=0.0005). Results were similar in the 2 groups regarding the type of toxicities.

Conclusions

Our results suggest similar efficacy of anti-vascular endothelial growth factor (VEGF) agents as first-line treatment for mRCC among younger and older patients with an age cut-off of 70 years. Safety results suggest that these drugs can be safely used for older patients with a need of caution regarding toxicity prevention.

SUBMITTER: Dupuis HGA

PROVIDER: S-EPMC8261413 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of anti-vascular endothelial growth factor therapies in older patients for first line treatment of metastatic renal cell carcinoma.

Dupuis Hugo Georges Arthur HGA Chebbi Ala A Surlemont Louis L Rigal Olivier O Di Fiore Frédéric F Pfister Christian C Nouhaud François-Xavier FX

Translational andrology and urology 20210601 6

<h4>Background</h4>immunotherapy became the first line treatment of metastatic renal cell carcinoma (mRCC). Nevertheless, a better understanding of the specificities of targeted therapies (TT) in the elderly population could be helpful in order to improve the management of mRCC in this population. The aim of this retrospective study was to assess efficacy and safety of sunitinib and sorafenib used as first-line TT in 70 years older patients compared to younger patients.<h4>Methods</h4>Data were ...[more]

PMID: 34295728

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Project description:AimThis study aimed to compare anti-epidermal growth factor receptor (anti-EGFR) therapy and anti-vascular endothelial growth factor therapy as first-line and second-line therapies in patients with KRAS exon 2 codon 12/13 wild-type (KRAS-WT) metastatic colorectal cancer (mCRC).MethodsMajor databases were systematically searched. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (95% CIs) were used to estimate the effect measures. Review Manager software version 5.3 was used for statistical analysis.ResultsSeven trials including ten articles were eligible in the meta-analysis. The patients treated with anti-EGFR as first-line therapy showed a longer overall survival (OS) for KRAS-WT and all RAS wild-type (RAS-WT) mCRC (HR =0.81, 95% CI: 0.72-0.92, P<0.01, n=5; HR =0.78, 95% CI: 0.66-0.93, P<0.01, n=3, respectively). The objective response rate (ORR) was better with the anti-EGFR therapy for KRAS-WT and all RAS-WT mCRC (OR =1.32, 95% CI: 1.11-1.56, P<0.01, n=5; OR =1.55, 95% CI: 1.21-2.00, P<0.01, n=3, respectively). There was no difference in progression-free survival (PFS) for KRAS-WT mCRC and all RAS-WT mCRC between the two groups (HR =1.00; 95% CI: 0.92-1.09, P=0.99, n=4; HR =0.92, 95% CI: 0.71-1.19, P=0.52, n=3, respectively). In addition, two trials provided data on the second-line therapy; there was no significant difference in OS and PFS for the second-line therapy, but a significant improvement in ORR was found in the anti-EGFR group (OR =1.91, 95% CI: 1.16-3.16, P=0.01, n=2). No difference in the conversion therapy (OR =1.34; 95% CI: 0.91-1.99; P=0.14, n=4) was observed between the two therapies.ConclusionOur results indicate that anti-EGFR therapy is superior to anti-vascular endothelial growth factor therapy for OS and ORR as a first-line therapy for KRAS-WT mCRC. In the second-line therapy, there was no significant difference in the survival outcomes on the basis of OS and PFS between the two groups. However, ORR improved significantly in the anti-EGFR group.

Project description:BackgroundThere is no cross-sectional comparison on therapeutic and adverse effects for treatments of metastatic castration-resistant prostate cancer (mCRPCa). We aimed to horizontally compare them for all common first-line and second-line therapies.MethodsWe conducted a network meta-analysis with a systematic review in four databases (Pubmed, Web of Science, Embase, and Cochrane Library) up to January 5th, 2025. All randomized controlled trials (RCT) related to mCRPCa treatments with a clear description in study design were included. Endpoints included the radiographic progression-free survival (rPFS), overall survival (OS), time to PSA progression (TTPP), PSA progression rate (PSARR), and adverse events. All data was extracted by two researchers and analyzed with Gemtc package in R and Stata15. This NMA protocol was registered online (ID: CRD42025633178).FindingsAfter screening among 33,694 articles, 24 RCTs involving 13,059 cases were included. For first-line treatments, combination therapies with second-generation androgen receptor inhibitors (ARIs) showed superior efficacies in OS [HR of poly(ADP-ribose) polymerase inhibitors (PARPi) + ARI: 0.63 (0.32,1.25)], TTPP [HR of Lu177 + ARI: 0.07 (0.01,0.87)] and PSARR [RR of Lu177 + ARI: 33.02 (15.56,71.62)] with the highest SUCRA (Surface under the Cumulative Ranking Curve) (72%, 91% and 97% respectively). PARPi + ARI also performed best for rPFS (SUCRA: 85%, with an insignificant HR [0.12 (0.02,2.35)]. For post-docetaxel second-line treatments, ARI also emerged as the preferred option. Efficacies of post-ARI second-line treatments were not evaluated due to the lack of related RCTs. No obvious heterogeneity and publication bias was detected during the therapeutic comparison.InterpretationThis study provided comparative evidence for first-line and post-chemotherapy second-line mCRPCa treatment options. Second-generation ARIs exhibited good efficacy, particularly when combined with other treatments. However, the safety analysis necessitated balance between benefits and adverse events, especially for combination therapies. Stronger evidence is needed through direct comparisons in future clinical trials.FundingThe study was supported by The National Natural Science Foundation of China (No. 82172568).

Project description:ContextConsiderable advances have been made in the first-line treatment of metastatic renal cell carcinoma (mRCC), with immunotherapy-based combinations including immunotherapy-tyrosine kinase inhibitors (IO-TKIs) and dual immunotherapy (IO-IO) favored. A lack of head-to-head clinical trials comparing these treatments means that there is uncertainty regarding their use in clinical practice.ObjectiveTo compare and rank the efficacy and safety of first-line systemic treatments for mRCC with a focus on IO-based combinations.Evidence acquisitionMEDLINE (Ovid), EMBASE, Cochrane Library, Web of Science, and abstracts of recent major scientific meetings were searched to identify the most up-to-date phase 3 randomized controlled trials (RCTs) of first-line IO-based combinations for mRCC up to June 2021. A systematic review and network meta-analysis were completed using the Bayesian framework. Primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), complete response (CR), grade 3-4 treatment-related adverse events (TRAEs), treatment-related drug discontinuation (TRDD), and health-related quality of life (HRQoL). The analysis was performed for the intention-to-treat (ITT) population as well as by clinical risk group.Evidence synthesisA total of six phase 3 RCTs were included involving a total of 5121 patients. Nivolumab plus cabozantinib (NIVO-CABO) had the highest likelihood of an OS benefit in the ITT population (surface under the cumulative ranking curve 82%). Avelumab plus axitinib (AVEL-AXI) had the highest likelihood of an OS benefit for patients with favorable risk (65%). Pembrolizumab plus AXI (PEMBRO-AXI) had the highest likelihood of an OS benefit for patients with intermediate risk (78%). PEMBRO plus lenvatinib (PEMBRO-LENV) had the highest likelihood of an OS benefit for patients with poor risk (89%). PEMBRO-LENV was associated with a superior PFS benefit across all risk groups (89-98%). Maximal ORR was achieved with PEMBRO-LENV (97%). The highest likelihood for CR was attained with NIVO plus ipilimumab (NIVO-IPI; 85%) and PEMBRO-LENV (83%). The highest grade 3-4 TRAE rate occurred with PEMBRO-LENV (95%) and NIVO-CABO (83%), but the latter was associated with the lowest TRDD rate (2%). By contrast, NIVO-IPI had the lowest grade 3-4 TRAE rate (6%) and the highest likelihood of TRDD (100%). HRQoL consistently favored NIVO-CABO (66-75%), PEMBRO-LENV (44-85%), and NIVO-IPI (65-93%) in comparison to the other treatments.ConclusionsIO-TKI drug combinations are associated with consistent improvements in clinically relevant outcomes for all mRCC risk groups. This benefit may be at the cost of higher TRAE rates; however, lower TRDD rates suggest a manageable side-effect profile. Longer follow-up is required to determine if the benefits of IO-TKIs will be sustained and if they should be favored in the first-line treatment of mRCC.Patient summaryCombination treatments based on immunotherapy agents continue to show meaningful benefits in the first-line treatment of metastatic kidney cancer. Our review and network meta-analysis shows that immunotherapy combined with another class of agents called tyrosine kinase inhibitors is promising. However, longer follow-up is needed for this treatment strategy to clarify if the benefits are long-lasting.

Project description:Purpose: Sorafenib and sunitinib are extensively used as first-line medications for metastatic renal cell carcinoma (mRCC). This meta-analysis was conducted to assess the antitumor efficacy, toxicity, and costs of the two drugs among mRCC patients. Materials and methods: PubMed, ScienceDirect, Scopus, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Google Scholar were searched for eligible articles. The endpoints consisted of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), adverse effects (AEs), and per-patient-per-month (PPPM) costs. Results: We included 14 studies with 2,925 patients. Both drugs were valid for treating mRCC with equivalent PFS [hazard ratio (HR) = 0.98, 95% confidence interval (CI): 0.88-1.10, P = 0.74] and disease control rates [DCRs; risk ratio (RR) = 1.03, 95% CI: 0.98-1.08, P = 0.28], but sunitinib had a better OS (HR = 1.10, 95% CI: 1.01-1.20, P = 0.04) and higher ORR (HR = 0.66, 95% CI: 0.45-0.97, P = 0.03) than sorafenib. Furthermore, sunitinib induced more incidences of severe hematologic AEs (anemia, neutropenia, and thrombocytopenia) and stomatitis/mucositis than sorafenib. In the subanalysis, Asian patients treated with sorafenib reported a longer PFS than those treated with sunitinib (HR = 0.87, 95% CI: 0.83-0.90, P = 0.01), and European patients treated with sunitinib had a longer OS than those treated with sorafenib (HR = 1.17, 95% CI: 1.01-1.30, P = 0.04). Moreover, the pooled results of the high-quality studies reported a higher ORR with sunitinib than with sorafenib, and medium-quality studies showed a longer OS with sunitinib than with sorafenib. Conclusions: Sunitinib has more benefits (longer OS and better ORR) than sorafenib as a first-line therapy for mRCC. However, sunitinib has higher toxicity than sorafenib. Sorafenib might be more suitable than sunitinib among Asian patients, and sunitinib might be superior to sorafenib in European patients. Nevertheless, more large-scale, high-quality studies are required.

Dataset Information

Efficacy and safety of anti-vascular endothelial growth factor therapies in older patients for first line treatment of metastatic renal cell carcinoma.

Background

Methods

Results

Conclusions

Publications

Efficacy and safety of anti-vascular endothelial growth factor therapies in older patients for first line treatment of metastatic renal cell carcinoma.

Similar Datasets

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