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Anticancer drugs approved by the Food and Drug Administration for gastrointestinal malignancies: Clinical benefit and price considerations.

ABSTRACT: BACKGROUND:The cost of new anticancer drugs is rising. We aimed to assess the clinical benefit and price of anti-cancer drugs approved by the US Food and Drug Administration (FDA) for advanced gastrointestinal cancers. METHODS:Drugs approved between 2006 and 2017 for advanced GI malignancies were identified from FDA.gov, and their updated supporting trial data were searched. Incremental clinical benefit was quantified by using ESMO Magnitude of Clinical Benefit Scale version 1.1 (grade 0-5) and ASCO Value Framework version 2 (score range -20 to 180). Higher scores indicate larger net benefit, and substantial benefit was defined as score 4 or 5 by the European Society for Medical Oncology (ESMO). The Micromedex REDBOOK was used to estimate the monthly average wholesale price (AWP) and total drug price (TDP) over the median treatment duration per patient. Clinical benefit, AWP and TDP of each drug class were assessed. RESULTS:In total, 16 GI cancer drugs received FDA approval for 24 indications, including five monoclonal antibodies (mAbs), five oral targeted therapies (TT), two immunotherapeutics (IO), three cytotoxic chemotherapies (CT), and one recombinant fusion protein (aflibercept). Most supporting trials (82%) reported overall survival benefit of less than 3 months and no significant improvement in quality of life. Only five agents (including one TT and one IO) with 21% the of approved indications met the ESMO's threshold of substantial clinical benefit. Median incremental benefit scores of TT and IO were comparable to other drug classes. However their median TDP was much higher at $153 402 and $98 208, respectively, compared to $30 330 USD per patient for CT. The estimated TDP did not correlate with clinical benefit scores. CONCLUSION:Most FDA-approved gastrointestinal cancer drugs do not meet the ESMO threshold of substantial clinical benefit. TT and IO are estimated to carry significant drug costs, and further cost analysis of these drugs is urgently needed.

SUBMITTER: Jiang DM

PROVIDER: S-EPMC6488126 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Project description:The discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs.In this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target-based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug-cancer associations (116, 87%) are supported by at least one clinical trial study.In this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its application to identify novel drug-cancer associations demonstrated that the data collected in this study is promising to serve as a fundamental for anticancer drug repurposing and development.

Project description:ImportanceEmerging policies drafted by the pharmaceutical industry indicate that they will transparently share clinical trial data. These data offer an unparalleled opportunity to advance evidence-based medicine and support decision-making.ObjectiveTo evaluate the eligibility of independent, qualified researchers to access individual participant data (IPD) from oncology trials that supported US Food and Drug Administration (FDA) approval of new anticancer medicines within the past 10 years.Design, setting, and participantsIn this quality improvement study, a cross-sectional analysis was performed of pivotal clinical trials whose results supported FDA-approved anticancer medicines between January 1, 2011, and June 30, 2021. These trials' results were identified from product labels.ExposuresEligibility for IPD sharing was confirmed by identification of a public listing of the trial as eligible for sharing or by receipt of a positive response from the sponsor to a standardized inquiry.Main outcomes and measuresThe main outcome was frequency of IPD sharing eligibility. Reasons for data sharing ineligibility were requested and collated, and company-, drug-, and trial-level subgroups were evaluated and presented using χ2 tests and forest plots.ResultsDuring the 10-year period examined, 115 anticancer medicines were approved by the FDA on the basis of evidence from 304 pharmaceutical industry-sponsored trials. Of these trials, 136 (45%) were eligible for IPD sharing and 168 (55%) were not. Data sharing rates differed substantially among industry sponsors, with the most common reason for not sharing trial IPD being that the collection of long-term follow-up data was still ongoing (89 of 168 trials [53%]). Of the top 10 anticancer medicines by global sales, nivolumab, pembrolizumab, and pomalidomide had the lowest eligibility rates for data sharing (<10% of trials).Conclusions and relevanceThere has been a substantial increase in IPD sharing for industry-sponsored oncology trials over the past 5 years. However, this quality improvement study found that more than 50% of queried trials for FDA-approved anticancer medicines were ineligible for IPD sharing. Data accessibility would be substantially improved if, at the time of FDA registration of a medicine, all data that support the registration were made available.

Project description:BackgroundIt is unknown to what extent cancer drugs approved in Switzerland by the Swissmedic fulfil criteria of clinical benefit according to the European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS), the American Society of Clinical Oncology Value Framework version 2 (ASCO-VF) and the Swiss OLUtool v2 (OLUtool).Patients and methodsAn electronic search identified studies that led to marketing authorisations in Switzerland 2010-2019. Studies were evaluated according to ESMO-MCBS, ASCO-VF and OLUtool. Substantial benefit for ESMO-MCBS, was defined as a grade A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. For ASCO-VF and OLUtool clinical benefit was defined as score ≥45 and A or B, respectively. Concordance between the frameworks was calculated with Cohen's Kappa (κ). Factors associated with clinical benefit were evaluated by logistic regression.ResultsIn the study period, 48 drugs were approved for 92 evaluable indications, based on 100 studies. Ratings for ESMO-MCBS, ASCO-VF and OLUtool could be performed for 100, 86, and 97 studies, respectively. Overall, 39 (39%), 44 (51%), 45 (46%) of the studies showed substantial clinical benefit according to ESMO-MCBS v1.1, ASCO-VF, OLUtool criteria, respectively. There was fair concordance between ESMO-MCBS and ASCO-VF in the palliative setting (κ = 0.31, P = 0.004) and moderate concordance between ESMO-MCBS and OLUtool (κ = 0.41, P<0.001). There was no significant concordance between ASCO-VF and OLUtool (κ = 0.18, P = 0.12). Factors associated with substantial clinical benefit in multivariable analysis were HRQoL benefit reported as secondary outcome for ESMO-MCBS and the ASCO-VF and blinded studies for OLUtool.ConclusionsAt the time of approval, only around half of the trials supporting marketing authorisation of recently approved cancer drugs in Switzerland meet the criteria for substantial clinical benefit when evaluated with ESMO-MCBS, ASCO-VF or OLUtool. There was at best only moderate concordance between the grading systems.

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Anticancer drugs approved by the Food and Drug Administration for gastrointestinal malignancies: Clinical benefit and price considerations.

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