Frontline<i>BRAF</i>Testing–Guided Treatment for Advanced Melanoma in the Era of Immunotherapies

Wu, Bin; Shi, Lizheng

doi:10.1001/jamadermatol.2020.2398

Cited by 16 publications

(20 citation statements)

References 28 publications

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“…Then, these reconstructed survival data were fit to four standard parametric models (exponential, Weibull, lognormal, and log-logistic), and the suitable survival distribution selected for each PFS curve based on the goodness of fit (Akaike information criterion). The PFS data of the sunitinib strategy in the five trials ( Motzer et al, 2018 ; Motzer et al, 2019 ; Powles et al, 2020 ; Choueiri et al, 2021 ; Motzer et al, 2021 ) and sorafenib in the two trials ( Motzer et al, 2014 ; Rini et al, 2020 ) were pooled, given the comparable trial eligibility criteria and patient baseline characteristics ( Supplementary Table S1 ) among the RCTs, similar to the analyses by Wu and Shi (2020) .…”

Section: Methodsmentioning

confidence: 99%

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies

Peng

et al. 2021

Front. Pharmacol.

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Background: Recent randomized controlled trials have demonstrated that immune checkpoint inhibitors (ICIs) improve patient outcomes, but whether these novel agents are cost-effective for untreated advanced renal cell carcinoma (aRCC) remains unclear.Materials and Methods: A microsimulation model was created to project the healthcare costs and outcomes of six strategies (lenvatinib-plus-pembrolizumab, nivolumab-plus-cabozantinib, nivolumab-plus-ipilimumab, pembrolizumab-plus-axitinib, avelumab-plus-axitinib, and sunitinib monotherapy) for patients with aRCC. Transition probability of patients was estimated from CLEAR, CheckMate 9ER, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, and other data sets by using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated from a United States payer perspective. One-way and probabilistic sensitivity analyses were performed, along with multiple scenario analyses, to evaluate model uncertainty.Results: Of the six competing strategies, nivolumab-plus-cabozantinib yielded the most significant health outcomes, and the sunitinib strategy was the least expensive option. The cost-effective frontier consisted of the nivolumab-plus-cabozantinib, pembrolizumab-plus-axitinib, and sunitinib strategies, which displayed the ordered ICERs of $81282/QALY for pembrolizumab-plus-axitinib vs sunitinib and $453391/QALY for nivolumab-plus-cabozantinib vs pembrolizumab-plus-axitinib. The rest of the strategies, such as lenvatinib-plus-pembrolizumab, nivolumab-plus-ipilimumab, and avelumab-plus-axitinib, were dominated. The cost of sunitinib drove the model most influentially.Conclusions: For aRCC, the pembrolizumab-plus-axitinib strategy is likely to be the most cost-effective alternative at the willingness-to-pay threshold of $100,000.

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Section: Methodsmentioning

confidence: 99%

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies

Peng

et al. 2021

Front. Pharmacol.

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“…There are already several different drugs that are available for the extraocular melanomas, such as BRAF inhibitors and c-KIT inhibitors, and it is possible repurpose them to treat CM [45][46][47]. These therapies are helping the management of melanomas, but they do not always induce remission.…”

Section: Discussionmentioning

confidence: 99%

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

Djulbegovic

Uversky

Harbour

et al. 2021

Genes

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In recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR®) and the Search Tool for the Retrieval of Interacting Genes (STRING®). Our PONDR® analysis found high levels of IDPRs in all five proteins with mutations linked to CM. The highest levels of IDPRs were in BRAF (45.95%), followed by PTEN (31.76%), NF1 (22.19%), c-KIT (21.82%), and NRAS (14.81%). Our STRING analysis found that each of these five proteins had more predicted interactions then expected (p-value < 1.0 × 10−16). Our analysis demonstrates that the mutations linked to CM likely affected IDPRs and possibly altered their highly complex PPIs. Quantifying IDPRs in BRAF, NRAS, c-KIT, NF1, and PTEN and understanding these protein regions are important processes as IDPRs can be possible drug targets for novel targeted therapies for treating CM.

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“…According to the CheckMate-227 trial ( Hellmann et al, 2019 ), nivolumab is given at a dose of 3 mg/kg of body weight every two weeks plus ipilimumab at a dose of 1 mg/kg every six weeks. The assumed mean body weights in the Unites States and China were 70 and 65 kg, respectively ( Wu et al, 2017 ; Wu and Shi, 2020 ). Treatment continued until disease progression or unacceptable toxicity or, for the immunotherapy regimens, until two years of follow-up ( Hellmann et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Cost-Effectiveness of Nivolumab Plus Ipilimumab as First-Line Therapy in Advanced Non–small-cell Lung Cancer

Hao

Shen

Wu³

2021

Front. Pharmacol.

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Purpose: The effectiveness of nivolumab plus ipilimumab for advanced non-small cell lung cancer (NSCLC) has been demonstrated. Decisions have to be made about allocating healthcare resources. Economic evidence could support policy decisions to fund expensive interventions. The current analysis evaluated the cost-effectiveness of nivolumab plus ipilimumab in advanced NSCLC harboring no EGFR or ALK mutations. It is set in the context of the US and China, representing developed and resource-constrained settings, respectively.Patients and Methods: A Markov model consisting of three discrete health states was used to assess the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy. The key clinical data were derived from the CheckMate-227 trial, and the cost and health preference data were derived from the literature. Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) were calculated for the two strategies. Subgroup, one-way and probabilistic sensitivity analyses were performed.Results: In the United States, nivolumab plus ipilimumab increased by 1.260 QALYs with an additional cost of $95,617 compared with the features of chemotherapy, which led to an ICER of $75,871 per QALY gained. INHB indicated that nivolumab plus ipilimumab treatment had a 99% probability of being cost-effective at the ICER threshold of $100,000/QALY in all subgroups. The results of sensitivity analyses revealed that the model outcomes were robust. In China, the ICER of nivolumab plus ipilimumab vs. chemotherapy was $59,773/QALY, and the INHB was -1.972 QALY at the threshold of $27,351/QALY.Conclusion: Nivolumab plus ipilimumab treatment is a cost-effective option compared with chemotherapy for patients with advanced NSCLC harboring no EGFR or ALK mutations in the United States. However, nivolumab plus ipilimumab is not a preferred option in China.

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FrontlineBRAFTesting–Guided Treatment for Advanced Melanoma in the Era of Immunotherapies

Cited by 16 publications

References 28 publications

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

Cost-Effectiveness of Nivolumab Plus Ipilimumab as First-Line Therapy in Advanced Non–small-cell Lung Cancer

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