Efficacy and safety of adjuvant targeted therapy for patients with non-distant metastasis renal cell carcinoma
0
Citation
0
Reference
20
Related Paper
Abstract:
Objective
To evaluate the efficacy and adverse events of adjuvant targeted therapy for non-distant metastatic renal cell carcinoma (ndmRCC).
Methods
A comprehensive literature search was conducted in PubMed, SpringerLink, Web of Science, and the Cochrane Library. All clinical randomized controlled trials on adjuvant targeting therapy for ndmRCC were retrieved. Literature screening, data extraction and literature quality evaluation were conducted by three researchers independently, and meta-analysis was performed using Review Manager Version 5.3. Outcomes we were interested in included progression-free survival (PFS), overall survival (OS), and adverse events.
Results
A total of 4 RCTs with 5 studies and 4 944 ndmRCC patients were selected for meta-analysis. Targeted adjuvant therapy improved the PFS of ndmRCC patients. The hazard ratio (HR) was 0.92(95%CI0.85-1.00, P =0.05) between the targeted therapy group and the placebo group. With the extension of follow-up, this effect was more significant, and the HR was 0.89(95%CI0.81-0.97, P=0.01). However, targeted adjuvant therapy did not extend the OS of ndmRCC patients, and the HR was 0.92(95%CI0.81-1.05, P=0.22). Compared with the placebo, targeted adjuvant therapy increased the incidence of adverse events and the number of patients who had to discontinue because of adverse events was also increased. The odds ratios were 6.03(95%CI5.30-6.86, P<0.001) and 7.65(95%CI6.31-9.26, P<0.001), respectively.
Conclusions
Targeted adjuvant therapy can improve the PFS of ndmRCC patients after surgery, but it cannot improve the OS. At the same time, it increases the incidence of adverse events.
Key words:
Renal cell carcinoma; Targeted adjuvant therapy; Meta-analysisKeywords:
Adjuvant Therapy
Targeted Therapy
Introduction: The Kidney Cancer Research Network of Canada (KCRNC) collaborated to prepare this consensus statement about the use of target agents as adjuvant therapy in patients with nonmetastatic renal cell carcinoma (nmRCC) after nephrectomy. We reviewed the published data and performed a meta-analysis of studies that focused on vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).Methods: A systematic literature search identified seven trials on adjuvant target therapy in nmRCC. Three trials, the ASSURE, S-TRAC, and PROTECT, focused on VEGFR TKIs and represented the focus of the study, including a meta-analysis combining their data on disease-free survival (DFS) and overall survival (OS).Results: The ASSURE trial showed no DFS or OS benefit of TKIs over placebo after one year of adjuvant sorafenib or sunitinib. In contrast, the S-TRAC trial showed improved DFS after one year of adjuvant sunitinib using central review process, but not using investigator review process. No OS benefit was recorded in either study. Recently, the PROTECT trial also showed no DFS or OS benefit when one year of adjuvant pazopanib was compared to placebo. Meta-analyses of the pooled DFS and OS estimates from all three trials resulted in DFS and OS hazard ratios of 0.87 (95% confidence interval [CI] 0.73‒1.04) and 1.04 (95% CI 0.89‒1.22), respectively.Conclusions: Data from three available clinical trials of adjuvant VEGFR TKIs vs. placebo do not currently support the use of adjuvant TKI therapy as standard of care after nephrectomy for nmRCC. At this time, adjuvant TKI-based adjuvant therapy is not recommended for routine use after nephrectomy for high-risk nmRCC, but highly motivated patients may benefit from a discussion with their oncologist regarding the risks and benefits of adjuvant TKI.
Pazopanib
Vandetanib
Kidney cancer
Adjuvant Therapy
Cite
Citations (17)
Regimen
Chemotherapy regimen
Targeted Therapy
Cite
Citations (9)
Background Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer. Methods From inception to January 2015, we searched for randomized, controlled trials (RCTs) using the following databases: PubMed, ScienceDirect, the Cochrane Library, Clinicaltrials.gov and EBSCO. Eligible trials included RCTs that evaluated standard chemotherapy which was either followed or not followed by targeted maintenance in patients with ovarian cancer who had been previously receiving adjunctive treatments, such as cytoreductive surgery and standard chemotherapy. The outcome measures included progression-free survival (PFS), overall survival (OS) and incidence of adverse events. Results A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria. The primary meta-analysis indicated that both PFS and OS were statistically and significantly improved in the targeted maintenance therapy group as compared to the control group (PFS: HR = 0.84, 95%CI: 0.75 to 0.95, p = 0.001; OS: HR = 0.91, 95%CI: 0.84 to 0.98, p = 0.02). When taking safety into consideration, the use of targeted agents was significantly correlated with increased risks of fatigue, diarrhea, nausea, vomiting, and hypertension. However, no significant differences were found in incidence rates of abdominal pain, constipation or joint pain. Conclusions Our results indicate that targeted maintenance therapy clearly improves the survival of ovarian cancer patients but may also increase the incidence of adverse events. Additional randomized, double-blind, placebo-controlled, multicenter investigations will be required on a larger cohort of patients to verify our findings.
Targeted Therapy
Maintenance therapy
Progression-free survival
Cite
Citations (12)
Targeted Therapy
Adjuvant Therapy
Kidney cancer
Cite
Citations (83)
Adjuvant Therapy
Aromatase inhibitor
Cite
Citations (6)
Adjuvant Chemotherapy
Adjuvant Therapy
Cite
Citations (81)
Background: At present, most of the targeted therapies for thyroid carcinoma are in the clinical trial stage, and there is still no strong evidence to confirm their clinical effect. The aim of this meta-analysis was to evaluate the outcome of targeted therapies and provide quantitative evidence. Method: Ovid, PubMed, EMBAS, ClinicalTrails.gov, and Cochrane Library electronic databases were searched until September 1, 2019. Randomized controlled studies (RCTs) studies that compared the treatment of thyroid carcinoma with the targeted therapies of utility and complications were analyzed. Results: The study included 5 studies with a total of 1,615 patients, with 991 cases in the drug group and 624 cases in the placebo group. The meta-analysis indicated that compared with the placebo group, the progression-free survival (PFS) rate of the drug group was significantly improved. The PFS of the drug group was 10.8 to 30.5 months, compared with 4 to 19.3 months for the placebo group (6 months PFS: OR =3.23, 95% CI: 2.57 to 4.05, P<0.00001, 12 months PFS: OR =3.38, 95% CI: 2.58 to 4.42, P<0.00001, 18 months PFS: OR =2.48, 95% CI: 1.74 to 3.54, P<0.00001). Overall survival (OS) did not differ significantly in the study (6 months: OR =1.53, 95% CI: 1.00 to 2.35, P=0.05, 12 months: OR =1.26, 95% CI: 0.94 to 1.69, P=0.12, 18 months: OR =1.11, 95% CI: 0.87 to 1.42, P=0.39). The incidence of adverse reactions in the drug group was significantly higher than that in the placebo group (OR =4.76, 95% CI: 3.45 to 6.57, P<0.00001), and the subgroup of adverse reactions was still significantly higher than that in the placebo group. Conclusions: This meta-analysis revealed that the targeted drugs can significantly prolong PFS in patients with thyroid carcinoma, but the targeted drugs did not prolong the OS. Although the incidence of adverse reactions was significantly higher than that of the placebo group, the patients were still tolerable in drug group.
Cite
Citations (2)
Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC. The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade. Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81–0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83–1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10–6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22–12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity. The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.
Adjuvant Therapy
Clinical endpoint
Forest plot
Cite
Citations (18)
Abstract S-1 monotherapy is widely used following gemcitabine failure in pancreatic cancer, especially in East Asia. We performed a meta-analysis to determine whether S-1-based combination therapy had better efficacy and safety compared with S-1 monotherapy. We searched Pubmed, Web of Science, ClinicalTrials.gov, and Cochrane CENTRAL and subsequently included five trials with a total of 690 patients. The combined hazard ratio (HR) or risk ratio; the corresponding 95% confidence intervals of progression-free survival, overall survival, and overall response rate; and grade 3–4 adverse events were examined. Five randomized controlled trials were included. Meta-analysis demonstrated S-1-based combination therapy significantly increased progression-free survival (HR = 0.78, 95% confidence interval [CI]: 0.67–0.90, p = 0.0009) and overall response rate (HR = 1.74, 95% CI: 1.20–2.52, p = 0.003). Evidence was insufficient to confirm that S-1-based combined regimens improved overall survival (HR = 0.87, 95% CI: 0.75–1.00, p = 0.05). There was no significant difference in adverse events between the two treatment arms. In conclusion, S-1-based combination therapy improved progression-free survival and overall response rate compared to S-1 monotherapy with acceptable toxicity.
Combination therapy
Progression-free survival
Cite
Citations (1)
The Accepted Manuscript version of this article (published on 24 October 2018) was withdrawn on 17 August 2021. Despite numerous attempts to contact the authors, the Editorial Office have not received a response from the authors regarding their article proofs since they received these on 9 November 2018.
Combination therapy
Maintenance therapy
Progression-free survival
Cite
Citations (2)