Efficacy, safety, and cost-effectiveness analysis of aflibercept in metastatic colorectal cancer: A rapid health technology assessment.

Background: Metastatic colorectal cancer (mCRC) imposes a heavy tumor burden worldwide due to limited availability of therapeutic drugs. Aflibercept, a kind of recombinant protein of the anti-vascular endothelial growth factor (VEGF) family, has been approved in clinical application among mCRC patients since 2012. A comprehensive analysis of the efficacy, safety, and cost-effectiveness of aflibercept in mCRC treatment is necessary. Objective: To evaluate the efficacy, safety, and cost-effectiveness of aflibercept for the treatment of mCRC in order to provide a decision-making reference for the selection of targeted drugs for second-line treatment of mCRC in Hong Kong, Macao, and Taiwan regions of China and the selection of new drugs for medical institutions in these regions. Methods: A systematic retrieve on databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu, as well as relevant websites and databases of health technology assessment including the National Institute of Health and Clinical Optimization, Centre for Evaluation and Communication at the University of York, and the Canadian Agency for Medicines and Health Technology, was conducted. The literature was screened according to the inclusion and exclusion criteria, and data were extracted and analyzed by two authors, while the quality of the literature was assessed. Results: Finally, we included two HTA reports, 11 systematic reviews/meta-analyses, and two cost-effectiveness studies in the rapid health technology assessment. For mCRC patients receiving second-line treatment, aflibercept combined with FOLFIRI significantly increased progression-free survival (PFS) and overall survival (OS) and the objective response rate (ORR) also improved, compared with folinic acid + fluorouracil + irinotecan (FOLFIRI). In terms of safety, mCRC patients who received aflibercept combined with FOLFIRI therapy had a higher incidence of grade 3-4 adverse events than those who received FOLFIRI alone, including anti-VEGF-related adverse events (hypertension, hemorrhagic events, and proteinuria) and chemotherapy-related adverse events (diarrhea, weakness, stomatitis, hand-foot syndrome, neutropenia, and thrombocytopenia). In terms of cost-effectiveness, two economic studies conducted in the United Kingdom and Japan, respectively, found that compared with FOLFIRI, aflibercept combined with FOLFIRI had no cost-effectiveness advantage in mCRC patients receiving second-line treatment. Conclusion: Compared with FOLFIRI treatment, aflibercept combined with FOLFIRI for the second-line treatment of mCRC patients has better efficacy, worse safety, and is not cost-effective. More high-quality clinical studies are required for further exploration of aflibercept's clinical value. Medical institutions in Hong Kong, Macao, and Taiwan regions of China should be cautious when using or introducing aflibercept plus FOLFIRI as a mCRC treatment.

Cost-effectiveness of pembrolizumab plus axitinib as first-line therapy for advanced renal cell carcinoma.

Aim: To evaluate the cost-effectiveness of first-line treatments for advanced renal cell carcinoma with pembrolizumab plus axitinib compared with sunitinib from the US payer perspective. Patients & methods: A Markov model was developed for this purpose. The clinical data were obtained from the KEYNOTE-426 trial. Utility values and direct costs related to the treatments were gathered from the published studies. Results: The incremental cost-effectiveness ratios of pembrolizumab plus axitinib versus sunitinib was $249,704 per quality-adjusted life year, which was higher than a willingness-to-pay threshold of $150,000 per quality-adjusted life year. Conclusion: Pembrolizumab plus axitinib was not considered to be cost-effective versus sunitinib as a first-line treatment for patients with advanced renal cell carcinoma from the US payer perspective.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy with PD-L1 test for the first-line treatment of NSCLC.

BACKGROUND: Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost-effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD-L1) test on the cost-effectiveness is also unknown. The current study assessed the cost-effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers' perspective. MATERIALS AND METHODS: A literature-based Markov model was conducted using KEYNOTE-189 trial data to compare cost and quality-adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro-chemotherapy combination and chemotherapy strategy without PD-L1 test, and treatment strategy according to their PD-L1 status. RESULTS: In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD-L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD-L1 test strategy. In the PD-L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD-L1 test strategy. Lowering Pembro price can also partly decrease the ICERs. CONCLUSION: Compared with chemotherapy, the combination strategy is not cost-effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD-L1 test for patient selection and price reduction could improve the cost-effective probabilities of immunotherapy for nonsquamous NSCLC.

Cost-effectiveness analysis of gemcitabine plus cisplatin versus fluorouracil plus cisplatin for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma.

PURPOSE: Compared with conventional fluorouracil plus cisplatin (FP) regimen, gemcitabine plus cisplatin (GP) can prolong survival in patients with recurrent or metastatic nasopharyngeal carcinoma, but the economic impact of this practice remains unknown. It's significant to evaluate its values by taking both efficacy and cost into consideration. METHODS: We developed a Markov model with 10 years horizon to compare the cost-effectiveness of GP and FP regimen. Clinical data came from a multicentre, randomised, open-label, phase 3 trial. Direct costs related to the treatment were estimated from the perspective of the Chinese healthcare system. Utility values were gathered from published study. Sensitivity analysis was conducted to confirm the robustness of the model. RESULTS: The total cost of FP regimen was $12,587 and yielded 0.964 QALYs, while the total cost of GP regimen was $17,920 and yielded 1.685 QALYs. The ICER of GP regimen versus FP regimen was $7,386 which was far less than the willingness-to-pay threshold ($26,508) in China. CONCLUSION: From the perspective of Chinese healthcare system, GP regimen with superior efficacy was proved to be more cost-effective than the traditional FP regimen. It is likely that GP regimen may be recommended as the primarily first-line treatment option for recurrent or metastatic nasopharyngeal carcinoma.

Ixazomib - the first oral proteasome inhibitor.

Ixazomib, as a proteasome inhibitor, inhibits the chymotrypsin-like activity of the ß5 subunit of the 20S proteasome. Based on the TOURMALINE-MM1 study, ixazomib was proved by the FDA as the orphan drug in November 2015. With a promising effect in prolonging the progression-free survival compared with placebo treatment (median: 20.6 versus 14.7 months), it was the first oral compound combined with lenalidomide and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior therapy. The main adverse events include low-grade hematological, digestive, or cutaneous events, which were manageable with care. Overall, ixazomib demonstrated favorable safety profile. Ongoing trials are conducted to define its place in first-line, maintenance, and relapse therapies. In this review, we summarized the clinical pharmacology, efficacy, tolerability, safety, and cost-effectiveness of ixazomib.

Cost-effectiveness of Daratumumab-based Triplet Therapies in Patients With Relapsed or Refractory Multiple Myeloma.

PURPOSE: The prominent efficacy of the addition of daratumumab to lenalidomide and dexamethasone (DRd) or the addition to bortezomib and dexamethasone (DVd) was proven previously for patients with relapsed or refractory multiple myeloma (RRMM). However, the cost-effectiveness of adding daratumumab to traditional doublet regimens versus doublet regimens alone (DRd vs Rd; DVd vs Vd) was unknown. METHODS: We developed a semi-Markov model by using a US payer perspective and 10-year time horizon to estimate the cost and quality-adjusted life years (QALYs) for treatments. Clinical data were obtained from the POLLUX (Phase 3 Study Comparing DRd Versus Rd in Subjects with Relapsed or Refractory Multiple Myeloma [RRMM]) and CASTOR (Phase 3 Study Comparing DVd Versus Vd in Subjects with RRMM) trials. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. FINDINGS: The incremental cost-effectiveness ratio (ICER) for DVd compared with Vd was $284,180 per QALY; the ICER for DRd compared with Rd was $1,369,062 per QALY. Only when the price of daratumumab was reduced to 37% (US $702/vial) of the current price could the addition of daratumumab to Vd be cost-effective under the US willingness-to-pay (WTP) of $50,000/QALY. However, under no discount level of the daratumumab price is the addition of daratumumab to Rd acceptable. When the WTP increased to $300,000/QALY, the addition of DVd had a 56.7% probability of being cost-effective compared with the Vd regimen. IMPLICATIONS: Due to the high price of daratumumab, neither the addition of daratumumab to Rd nor Vd proved to be cost-effective under US WTP. However, if the daratumumab price fell to a certain discount level, the DVd regimen might be cost-effective.

Life Strain, Social Control, Social Learning, and Delinquency: The Effects of Gender, Age, and Family SES Among Chinese Adolescents.

Very few studies have examined the pathways to delinquency and causal factors for demographic subgroups of adolescents in a different culture. This article explores the effects of gender, age, and family socioeconomic status (SES) in an integrated model of strain, social control, social learning, and delinquency among a sample of Chinese adolescents. ANOVA is used to check for significant differences between categories of demographic groups on the variables in the integrated model, and the differential effects of causal factors in the theoretical path models are examined. Further tests of interaction effects are conducted to compare path coefficients between "high-risk" youths (i.e., male, mid-teen, and low family SES adolescents) and other subgroups. The findings identified similar pathways to delinquency across subgroups and clarified the salience of causal factors for male, mid-teen, and low SES adolescents in a different cultural context.

Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese.

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair and plays an important role in the maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function and repair capacity of XRCC1 protein which further results in the genetic instability and lung carcinogenesis. Previous studies investigating the relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese yielded contradictory results. A meta-analysis was performed to clarify the effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95% confidence intervals (95%CI). Nineteen studies with a total of 12,835 participants were included into this meta-analysis. Overall, there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models (Gln vs. Arg: OR = 1.13, 95%CI 1.01-1.25, P = 0.029; GlnGln vs. ArArg: OR = 1.41, 95%CI 1.07-1.84, P = 0.013; GlnGln vs. ArArg/ArgGln: OR = 1.37, 95%CI 1.07-1.76, P = 0.013). Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models. There was no obvious risk of bias in the meta-analysis. Data from the current meta-analysis support the obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer in Chinese.