Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

<p>Abstract</p> <p>Background</p> <p>Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting.</p> <p>Methods</p> <p>Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy) versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS), disease-free survival (DFS), and severe toxicities. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I². Different strategies of adjuvant treatment were evaluated separately.</p> <p>Results</p> <p>Ten studies (2,609 patients) were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I²= 0%) or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I²= 15%) when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy) had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group.</p> <p>Conclusions</p> <p>This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.</p

Systematic review and meta-analysis of incremental cost-effectiveness ratio (ICER) for new cancer drugs

66 Background: This systematic review and meta-analysis compared incremental cost-effectiveness ratios (ICERs) of cancer drugs and their relationship with society’s willingness to pay (WTP) across different countries, scenarios and indications. Methods: We sought for cost-effectiveness studies in PubMed, Embase, Cochrane and LILACS published from December 2012 to December 2017. CAR-T cell therapies were excluded given short follow-up. We converted ICERs value and respective annualized 1time the Gross Domestic Product per capita (GDP) - used as a proxy for WTP threshold - into purchase-parity-power dollars (PPP) for better economic reality comparisons. Economics data came from the International Monetary Fund website. Characteristics studied in the distribution of ICERs values were compared using the Mann-Whitney or Kruskal-Wallis U-test with multiple comparison correction and simple linear regression. The chance of ICER being below the 1x GDP threshold was expressed as odds ratio and 95% confidence interval, calculated by logistic regression. Results: We retrieved 354 drug-versus-drug different assessments. PPPconversion increased median ICER of middle-income countries ($32k to$68k;P < 0.001). Median ICER was highest in USA ($154k), followed by other high-income countries ($76k; P < 0.001). In multiple regression, anti-VEGF (P < 0.001) and US-led (P = 0.03) studies had highest ICERs, while curative therapies (p = 0.02) had the lowest ones. 22% of studies were below the WTP bar, none of anti-VEGF, sipuleucel, anti-CD-30, castration-resistant, hepatocarcinoma, and renal cell ones. Immune checkpoint inhibition (OR 8.70; P = 0.045) and middle-income (OR 7.40; P < 0.001) studies were more likely above WTP, whereas curative therapies were more likely below WTP. Conclusions: Cancer therapies’ cost exceeding the WTPs is a worldwide pattern, with some factors related to ICER variation. These findings may foster better understanding and aid stakeholders deal with the global issue of high oncology care costs