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Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval. Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000–2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response's relative risk (RR) alongside objective response rate (ORR) were meta-analyzed. Results: The median development time for breast cancer drugs was 7.8 years (95% CI 6.2–10.8). 26% of treatments were considered innovative ("first-in-indication") with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA's special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417–752) at 181 centers (IQR 142–223) across 19 countries (IQR 17–20). New drugs' HR were 0.78 for OS (95% CI 0.74–0.82) and 0.59 for PFS (95% CI 0.54–0.64) with a RR for tumor response of 1.61 (95% CI 1.46–1.76). Median improvements of OS were 2.8 months (IQR 1.8–5.8) and PFS were 4.4 months (IQR 2.2–7.1). In single-arm trials, the average ORR was 31% (95% CI 10–53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a 'high-value' ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097–17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840–86,062). Conclusions: Over the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life. [ABSTRACT FROM AUTHOR]

Background: The cost of cancer drugs presents a significant challenge to accessibility of treatment worldwide. Projections indicate that by 2040, two-thirds of cancer cases will occur in low- and middle- income countries. Paradoxically, despite this impending burden, LMICs command less than 5% share of global resources for treating cancer. Morocco, like many LMICs, faces significant obstacles in providing innovative cancer treatments to its population. Aim: Firstly, we aimed to conduct an original research investigating the availability and affordability of innovative cancer drugs in Morocco. Secondly, we sought to review the broader market dynamics, pricing, and reimbursement policies in the country. Methods: For the first objective, we identified a preliminary list of medicines approved for oncological indications in the Moroccan market based on resources from ANAM (National Agency for Health Insurance), pharmacy regulators, and online resources that compile information on approved medicines. For the second objective, we exhaustively reviewed the regulatory documents, legal texts and grey literature reports. All the informations were examined by pharma delegates and local experts. Results: As of January 2024, Morocco has 39 innovative anticancer medicines with market authorization. 30% of these drugs were approved after 2020. The majority of approved drugs were for breast, lung, colorectal, and prostate cancer. The period between FDA approval and entry into the Moroccan market ranges from 2 to 7 years, with a median of 3 years for breast cancer drugs and 7 years for more expensive drugs like Olaparib and Osimertinib. 22 out of the 39 drugs are not reimbursed, with an average reimbursement time of 4 years. Compared to prices in France, the most notable pricing disparities concern immunotherapy agents, priced 600 to 900 euros lower in France, while drugs like Pazopanib and Erlotinib cost 50% less in Morocco. Conclusion: Our study reveals significant disparities in the availability and affordability of innovative cancer drugs in Morocco. Regulatory hurdles, importation challenges, and pricing strategies contribute to this inequitable landscape. Addressing systemic barriers, fostering collaborations between stakeholders, and adopting a value-based pricing approach are imperative steps toward ensuring equitable access to high-quality interventions for patients, regardless of their geographical location. [ABSTRACT FROM AUTHOR]

Objectives This cross-sectional study examines the Food and Drug Administration (FDA)'s Accelerated Approval (AA) pathway for cancer drugs from 1992 to 2021, which expedites the development and approval of new drugs, including biologics, for severe or life-threatening conditions such as cancers. Methods Based on the 'CDER Drug and Biologic AAs Based on a Surrogate Endpoint' report, the number of indications where anticancer agents received AA and the conversion rates to Full Approval (FA) were analysed. Outcome measures used in phase II and phase III trials for these drugs were obtained from US National Library of Medicine for comparison. Key findings Of the 278 AA-granted indications, 67% were for anticancer agents. Lymphoma, leukemia, and lung cancer had the highest number of AA indications among all cancer types. The conversion rates to FA varied among periods: Early (1995–2003), Middle (2004–2012), and Late (2013–2021). The conversion rates for drugs were 82%, 79%, and 31%, while biologics exhibited rates of 100%, 78%, and 27%, respectively. The overall response rate was often the primary outcome measure in phase II trials, whereas overall survival and progression-free survival were the common outcome measures in phase III trials. Secondary outcome measures included disease control rate and duration of response. Conclusions This study provides valuable insights for stakeholders seeking to understand the approval criteria and processes for cancer drugs via the AA pathway. However, limitations in data availability, phase-specific variations in drug doses and combinations, and the inability to manage uncertain data should be acknowledged. Research on the AA program to non-cancer drugs is also required. [ABSTRACT FROM AUTHOR]

Abstract Background The cost of cancer drugs presents a significant challenge to accessibility of treatment worldwide. Projections indicate that by 2040, two-thirds of cancer cases will occur in low- and middle- income countries. Paradoxically, despite this impending burden, LMICs command less than 5% share of global resources for treating cancer. Morocco, like many LMICs, faces significant obstacles in providing innovative cancer treatments to its population. Aim Firstly, we aimed to conduct an original research investigating the availability and affordability of innovative cancer drugs in Morocco. Secondly, we sought to review the broader market dynamics, pricing, and reimbursement policies in the country. Methods For the first objective, we identified a preliminary list of medicines approved for oncological indications in the Moroccan market based on resources from ANAM (National Agency for Health Insurance), pharmacy regulators, and online resources that compile information on approved medicines. For the second objective, we exhaustively reviewed the regulatory documents, legal texts and grey literature reports. All the informations were examined by pharma delegates and local experts. Results As of January 2024, Morocco has 39 innovative anticancer medicines with market authorization. 30% of these drugs were approved after 2020. The majority of approved drugs were for breast, lung, colorectal, and prostate cancer. The period between FDA approval and entry into the Moroccan market ranges from 2 to 7 years, with a median of 3 years for breast cancer drugs and 7 years for more expensive drugs like Olaparib and Osimertinib. 22 out of the 39 drugs are not reimbursed, with an average reimbursement time of 4 years. Compared to prices in France, the most notable pricing disparities concern immunotherapy agents, priced 600 to 900 euros lower in France, while drugs like Pazopanib and Erlotinib cost 50% less in Morocco. Conclusion Our study reveals significant disparities in the availability and affordability of innovative cancer drugs in Morocco. Regulatory hurdles, importation challenges, and pricing strategies contribute to this inequitable landscape. Addressing systemic barriers, fostering collaborations between stakeholders, and adopting a value-based pricing approach are imperative steps toward ensuring equitable access to high-quality interventions for patients, regardless of their geographical location.

Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller proteins. Here, we obtain structures of small proteins by binding them to a rigid molecular scaffold based on a designed protein cage, revealing atomic details at resolutions reaching 2.9 Å. We apply this system to the key cancer signaling protein KRAS (19 kDa in size), obtaining four structures of oncogenic mutational variants by cryo-EM. Importantly, a structure for the key G12C mutant bound to an inhibitor drug (AMG510) reveals significant conformational differences compared to prior data in the crystalline state. The findings highlight the promise of cryo-EM scaffolds for advancing the design of drug molecules against small therapeutic protein targets in cancer and other human diseases.

This study introduces a new electrochemical platform for the rapid and sensitive detection of the potent anticancer drug epirubicin (EPB) in blood plasma. The platform utilizes a graphene/Zinc Oxide (ZnO) nanoparticle nanocomposite modified glassy carbon electrode (GCE), which was synthesized through a simple one-pot method where ZnO nanoparticles were dispersed onto graphene sheets. The graphene/ZnO/GCE nanocomposite was characterized using advanced techniques such as FE-SEM, EDS, XRD, FT-IR, and XPS in order to analyze its structural properties. The graphene/ZnO/GCE electrode exhibited minimal interference and demonstrated high selectivity and sensitivity in detecting EPB. The sensor's selectivity was validated by a recovery rate exceeding 98.40 % and a relative standard deviation below 4.65 %. The limits of detection and quantification were determined to be 6.0 nM and 9.0 nM, respectively, indicating the sensor's high sensitivity within a practical concentration range. With a sensitivity of 1.09509 µA/µM, the sensor exhibited a linear response to EPB concentrations ranging from 4.0 to 730.0 μM. Furthermore, successful detection of EPB in serum samples with a recovery rate exceeding 98.40 % underscores the practical utility of the graphene/ZnO/GCE sensor. The detailed characterization of the graphene/ZnO/GCE nanocomposite provides insights into its structural and chemical attributes, furthering its potential for biomedical applications.

Introduction: Advancements in oncology have revolutionized cancer treatment, with new drugs being approved at different rates worldwide. Our objective was to evaluate the approval of new oncological drugs for solid tumors by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA) since 2008. Methods: Data were collected from public and online databases by searching for the date of submission, the date of the procedure, the date of approval, clinical indication, and drug characteristics. The distribution was tested using the Shapiro–Wilk, test and comparisons were made using the Mann–Whitney U test; the data are reported using median days and interquartile range (IQR1–IQR3). Results: In total, 104 new oncologic drugs for the treatment of solid tumors were approved by the three agencies: 98 by the FDA, 90 by the EMA, and 68 by ANVISA. The cancer types with the highest number of first indications were lung cancer (n = 24), breast cancer (n = 15), and melanoma (n = 15). Most approvals were for oral medications (n = 63) and tyrosine–kinase inhibitors or other small-molecule inhibitors (n = 54). Time to approval after submission was as follows: the FDA—224 days (167–285); the EMA—364 days (330–418); and ANVISA—403 days (276–636) (p < 0.00001 for the FDA to the EMA and the FDA to ANVISA). The difference between submission dates among the agencies was as follows: EMA–FDA: 24 days (0–85); ANVISA–FDA: 255 (114–632); and ANVISA–EMA: 260 (109–645). The difference in approval dates between the agencies was as follows: EMA–FDA: 185 days (59–319); ANVISA–FDA: 558 (278–957); and ANVISA–EMA: 435 days (158–918). Conclusions: New oncologic drugs are submitted to the FDA and EMA for approval on similar dates; however, the longer appraisal period by the EMA pushes the approval date for Europe to approximately 6 months later. The same steps at ANVISA delay the approval by 1.5 years. Such procedures cause a significant difference in available medications between these regions.

Terpenoid indole alkaloids (TIAs) are natural compounds found in medicinal plants that exhibit various therapeutic activities, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, anti-helminthic, and anti-tumor properties. However, the production of these alkaloids in plants is limited, and there is a high demand for them due to the increasing incidence of cancer cases. To address this research gap, researchers have focused on optimizing culture media, eliciting metabolic pathways, overexpressing genes, and searching for potential sources of TIAs in organisms other than plants. The insufficient number of essential genes and enzymes in the biosynthesis pathway is the reason behind the limited production of TIAs. As the field of natural product discovery from biological species continues to grow, endophytes are being investigated more and more as potential sources of bioactive metabolites with a variety of chemical structures. Endophytes are microorganisms (fungi, bacteria, archaea, and actinomycetes), that exert a significant influence on the metabolic pathways of both the host plants and the endophytic cells. Bio-prospection of fungal endophytes has shown the discovery of novel, high-value bioactive compounds of commercial significance. The discovery of therapeutically significant secondary metabolites has been made easier by endophytic entities' abundant but understudied diversity. It has been observed that fungal endophytes have better intermediate processing ability due to cellular compartmentation. This paper focuses on fungal endophytes and their metabolic ability to produce complex TIAs, recent advancements in this area, and addressing the limitations and future perspectives related to TIA production. [ABSTRACT FROM AUTHOR]

Introduction: Advancements in oncology have revolutionized cancer treatment, with new drugs being approved at different rates worldwide. Our objective was to evaluate the approval of new oncological drugs for solid tumors by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA) since 2008. Methods: Data were collected from public and online databases by searching for the date of submission, the date of the procedure, the date of approval, clinical indication, and drug characteristics. The distribution was tested using the Shapiro–Wilk, test and comparisons were made using the Mann–Whitney U test; the data are reported using median days and interquartile range (IQR1–IQR3). Results: In total, 104 new oncologic drugs for the treatment of solid tumors were approved by the three agencies: 98 by the FDA, 90 by the EMA, and 68 by ANVISA. The cancer types with the highest number of first indications were lung cancer (n = 24), breast cancer (n = 15), and melanoma (n = 15). Most approvals were for oral medications (n = 63) and tyrosine–kinase inhibitors or other small-molecule inhibitors (n = 54). Time to approval after submission was as follows: the FDA—224 days (167–285); the EMA—364 days (330–418); and ANVISA—403 days (276–636) (p < 0.00001 for the FDA to the EMA and the FDA to ANVISA). The difference between submission dates among the agencies was as follows: EMA–FDA: 24 days (0–85); ANVISA–FDA: 255 (114–632); and ANVISA–EMA: 260 (109–645). The difference in approval dates between the agencies was as follows: EMA–FDA: 185 days (59–319); ANVISA–FDA: 558 (278–957); and ANVISA–EMA: 435 days (158–918). Conclusions: New oncologic drugs are submitted to the FDA and EMA for approval on similar dates; however, the longer appraisal period by the EMA pushes the approval date for Europe to approximately 6 months later. The same steps at ANVISA delay the approval by 1.5 years. Such procedures cause a significant difference in available medications between these regions. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions to anticancer drugs include treatment‐limiting toxicity. Standard drug desensitisation offers temporary tolerance and hence requires repetition. We used omalizumab, an anti‐immunoglobulin E antibody, to overcome immediate and delayed hypersensitivity reactions to various anticancer drugs. Seven of the eight patients in the current study successfully resumed the desired anticancer drug regimen without standard desensitisation. No safety issues from omalizumab were observed. [ABSTRACT FROM AUTHOR]

PD-L1 is a key immunotarget involved in binding to its receptor PD-1. PD-L1/PD-1 interface blocking using antibodies (or small molecules) is the central area of interest for tumor suppression in various cancers. Blocking the PD-L1/PD-1 pathway in the tumor cells results in its immune activation and destruction, and thereby restoring the T-cell proliferation and cytokine production. The active binding site interface residues of PD-L1/PD-1 were experimentally known and proven by structural biology and site-directed mutagenesis studies. Structure-based molecular design technique was employed to identify the inhibitors for blocking the PD-L1/PD-1 interface. Nine hits to leads were identified from the SPECS small molecule database by machine learning, molecular docking, and molecular dynamics simulation techniques. Following this, a machine learning-assisted QSAR modeling approach was implemented using ChEMBL database to gain insights into the inhibitory potential of PD-L1 inhibitors and predict the activity of our previously screened nine hit molecules. The best leads identified in the present study bind strongly with the active sites of PD-L1/PD-1 interface residues, which include A121, M115, I116, S117, I54, Y56, D122, and Y123. These computational leads are considered promising molecules for further in vitro and in vivo analysis to be developed as potential PD-L1 checkpoint inhibitors to cure different types of cancers. [ABSTRACT FROM AUTHOR]

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. Results In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending. [ABSTRACT FROM AUTHOR]

Simple Summary: The majority of oncology drugs approved by the Food and Drug Administration over the past quarter century have been targeted therapies, designed to act on cancer cells with specific molecular abnormalities. Although these newer agents have different properties compared to cytotoxic chemotherapy, the same methodology used for dose-finding during drug development has continued to be used. Growing awareness of the inadequacy of traditional dose selection processes for modern cancer drugs has been the catalyst for the creation of new regulatory guidance aimed at reforming current practices. This review summarizes six cases, illustrating different approaches to targeted therapy dose optimization. Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest proportion of oncology drugs approved by the United States (US) Food and Drug Administration (FDA) over the past 25 years and have become the standard of care for the treatment of many cancers. However, despite the metamorphosis of the therapeutic landscape, some aspects of cancer drug development have remained essentially unchanged. In particular, the dose-finding methodology originally developed for cytotoxic chemotherapy drugs continues to be implemented, even though this approach no longer represents the most appropriate strategy for modern cancer therapies. In recognition of the need to reconsider assumptions, adapt the dose selection process for newer drugs, and design alternative strategies, the FDA has undertaken several initiatives in recent years to address these concerns. These actions include the launch of Project Optimus in 2021 and the issuance of draft guidance for industry on dose optimization of oncology drugs in 2023. Amid this evolving regulatory environment, the present manuscript reviews case studies for six different targeted cancer therapies, highlighting how dose-finding challenges have been managed to date by oncologists, sponsors, and regulators. [ABSTRACT FROM AUTHOR]

The article examines the drug pricing policy and cost containment measures in India by drawing on the data of spending on and price variations of cancer drugs. Results show that medicines held the highest share in the out-of-pocket (OOP) cancer medical expenditure in private and public sectors, and it was more pronounced for private sector and in outpatient care. Medicine expenditure has a positive and significant causal association to OOP medical expenditure of cancer patients even when other medical costs, type of care and socio-economic backgrounds are controlled for. Further, there were significant price variations for recently approved anticancer medicines across brands, which are under and outside price control. The results confirm the ineffectiveness of price control measures for cancer drugs under market-based pricing policy and the inadequacy of existing risk protection measures in India. This calls for the adoption of appropriate cost containment measures, which include expanding the scope of all forms, types and severities of cancer and anticancer medications under health insurance and adoption of a uniform treatment protocol across private and public sectors. [ABSTRACT FROM AUTHOR]

Copay accumulator programs, which exclude the benefit of manufacturer patient assistance from annual maximum out‐of‐pocket costs, shift costs for expensive oncology drugs from plans to patients. Legislation is ongoing to protect patients from these potentially harmful redefinitions of cost‐sharing. [ABSTRACT FROM AUTHOR]

Introduction: Compounding robots are increasingly being implemented in hospital pharmacies. In our hospital, the recent acquisition of a robot (RIVATM, ARxIUM) for intravenous cancer drug compounding obliged us to replace the previously used infusion devices. The objective of the present study was to assess and qualify the new intravenous sets prior to their use in our hospital and prior to the implementation of the compounding robot. Materials and Methods: The ChemoLockTM (ICU Medical) was compared with the devices used previously for compounding (BD PhaSealTM, Becton-Dickinson) and infusion (Connect-ZTM, Codan Medical). The connection/disconnection of infusion devices to/from 50 mL infusion bags was tested with a dynamometer (Multitest-i, Mecmesin). Leakage contamination was visualized by a methylene blue assay and was quantified in simulated pump infusions with 20 mg/mL quinine sulfate (N = 36/group); after the analytical assay had been validated, quinine was detected by UV-spectrophotometry at 280 and 330 nm. Groups were compared using chi-squared or Mann–Whitney U tests. Results: The connection/disconnection test showed that although all the devices complied with the current standard, there was a statistically significant difference in the mean ± standard deviation compression force (51.5 ± 11.6 for the Connect-ZTM vs. 60.3 ± 11.7 for the ChemoLockTM; p = 0.0005). Leaks were detected in 32 (29.1%) of the 110 tests of the ChemoLockTM. The contamination rates were also significantly different: 13.9% for the BD PhaSealTM versus 75.0% for the ChemoLockTM; p < 0.0001). Discussion/conclusion: Our results showed that the new infusion device complied with current standards. However, the presence of contamination emphasizes the need for operators to use the recommended personal protective equipment. Further studies of contamination with cancer drugs are required. [ABSTRACT FROM AUTHOR]

Abstract Background Although the number of cancer clinical drug trials is increasing rapidly in China, issues concerning informed consent in this research context are understudied. By performing a narrative literature review, we aim to describe the current situation and identify the most salient challenges affecting informed consent in cancer clinical drug trials among adult patients in China since 2000. Methods We searched Web of Science (WOS), PubMed, Scopus, EMBASE, the Cochrane Library databases, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database on Disc (CBMdisc), Chinese Scientific Journals Fulltext Database (CQVIP), and WANFANG Data to identify relevant publications since 2000. Data were extracted by three reviewers on six items pertaining to study type, theme, and challenges. Results We identified 37 unique manuscripts, from which 19 full texts were obtained and six were included in the review. All six studies were published in Chinese journals, and the publication years of the majority (five out of six) of the studies were 2015 or later. The authors of the six studies were all from clinical departments or ethical review committees at five hospitals in China. All of the included publications were descriptive studies. Publications reported challenges related to the following aspects of informed consent: information disclosure, patient understanding, voluntariness, authorization, and procedural steps. Conclusion Based on our analysis of publications over the past two decades, there are currently frequent challenges related to various aspects of informed consent in cancer clinical drug trials in China. Furthermore, only a limited number of high-quality research studies on informed consent in cancer clinical drug trials in China are available to date. Efforts toward improvement of informed consent practice, in the form of guidelines or further regulations in China, should draw on both experience from other countries and high-quality local evidence.

Rising cancer drug prices challenge patients and healthcare systems. Although prices are routinely assigned to original drug indications receiving US Food and Drug Administration (FDA) approval, the pricing of supplemental indication approvals remains uncertain. This study identifies and quantifies factors associated with cancer drug prices, distinctly analyzing original and supplemental indications. Clinical trial evidence and epidemiologic data supporting new indications' FDA approval (2003-2022) were collected from the Drugs@FDA database, ClinicalTrials.gov , and Global Burden of Disease study. Indication-specific monthly treatment costs were calculated for Medicare patients. The association between log-prices and collected variables were assessed in regression analyses. We identified 145 drugs approved across 373 cancer indications. Drugs were priced at $24 444 per month on average (median = $16 013). For original indications, prices weakly correlated to improvements in overall survival (β = 0.28, P =.037) and progression-free survival (β = 0.16, P =.001). Original indications' prices were as follows: (1) negatively associated with disease incidence (β = −0.21, P <.001) and prevalence; (2) positively correlated with first-in-class drugs (26%, P =.057), gene and cell therapies (176%, P <.001), hematologic cancers (62%, P <.001), and severe diseases with substantial unmet needs (6% per disability-adjusted life-year, P <.001); and (3) negatively correlated to indications with randomized-controlled phase 3 trials. Prices were poorly associated with supplemental indications' efficacy, clinical evidence, and epidemiology. Cancer drug prices are set based on the original indication's characteristics, thereby omitting the value of supplemental indications. Indication-specific pricing, coverage, and reimbursement policies considering each indication's safety, efficacy, innovativeness, and unmet needs are necessary to align a drug's value and price. • Cancer drug prices are a leading contributor to growing healthcare expenditure in the United States with unaffordable drugs' financial toxicity adversely affecting treatment adherence and patient survival. Previous studies found cancer drug prices are not aligned with the clinical benefit they offer; however, these studies are limited to original drug approvals. After the US Food and Drug Administration first approves a drug in its original indication, sponsors submit additional evidence to extend a drug's use to supplemental indications. • For original indications, drug prices are not aligned with the survival benefit they offer to patients but the unmet medical needs they fill and the biotechnological innovation they achieve. Albeit the majority of cancer drugs are US Food and Drug Administration-approved for multiple indications, drug prices were not correlated with the efficacy, clinical evidence, and epidemiology offered by supplemental indications. • In summary, cancer drug prices are set based on the original indication's characteristics, thereby omitting the value of supplemental indications. Indication-specific pricing, coverage, and reimbursement policies considering each indication's safety, efficacy, innovativeness, and unmet needs are necessary to reconcile the disconnect between a medicine's costs and value. [ABSTRACT FROM AUTHOR]

Rapid increase in cost continues to have negative impact on patients’ accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a university hospital to tackle this imbalance and strive to provide high quality, sustainable, affordable and accessible care. An active approach in cost containment of expensive and innovative cancer drugs was adopted in our organisation to safeguard accessibility and improve quality of life for patients. In this article, we described four inverventions: 1) identify right patient and minimise overtreatment, 2) in-house medicine production for selected indications, 3) minimise medicine spillages and 4) effective procurement strategies. We call on other hospitals to take action and, favourably, to collaborate on a European level. Together, we will safeguard the current and future care of our patients. [ABSTRACT FROM AUTHOR]

Abstract Background Litigation for health care, also known as health judicialization, is frequent in Brazil. It involves recourse to the court system to access health services. The study aimed to evaluate whether cancer patients in Belo Horizonte, Minas Gerais, Brazil, increased their overall survival by increasing access to certain drugs or treatments through litigation, controlling for the effect of demographic and disease-related variables. Methods A retrospective cohort study was conducted. Patients with breast, prostate, brain, lung, or colon cancers from 2014 to 2019 were included. Survival analysis was performed using the Cox proportional hazards model. Results In the multivariate analysis, litigation was significantly associated with increased survival in cancers of breast (HR = 0.51, 95%CI 0.33–0.80), prostate (HR = 0.50, 95%CI 0.30–0.85), colon (HR = 0.59, 95%CI 0.38–0.93), and lung (HR = 0.36, 95%CI 0.22–0.60). Five-year survival rates of patients who sued for treatment were 97.8%, 88.7%, 59.3%, and 26.0%, compared to median survival of 95.7%, 78.7%, 41.2%, and 2.4%, respectively, among patient that did not resort to court action. The study suggests that litigation for access to cancer treatment may represent a step forward in obtaining more effective treatment. This study´s main limitations are the lack of patients´ clinical information for use as control variables and the lack of variables to assess patients´ quality of life. The study also found that many cases involved claims that could have been solved by administrative rather than legal action. Some claims thus reflect the lack of adequate administrative procedures. Conclusion When based on scientific evidence, access to new therapies, combined with other technologies already available, can favor patient survival. Access to new therapies through litigation may increase health inequalities since low-income patients have limited access to legal recourse against the State to meet their needs. The timely approval of new effective therapies can mitigate the judicialization of cancer treatment.

Cardiovascular disease (CVD) complications have contributed significantly toward poor survival of cancer patients worldwide. These complications that result in myocardial and vascular damage lead to long-term multisystemic disorders. In some patient cohorts, the progression from acute to symptomatic CVD state may be accelerated due to exacerbation of underlying comorbidities such as obesity, diabetes and hypertension. In such situations, cardio-oncologists are often left with a clinical predicament in finding the optimal therapeutic balance to minimize cardiovascular risks and maximize the benefits in treating cancer. Hence, prognostically there is an urgent need for cost-effective, rapid, sensitive and patient-specific screening platform to allow risk-adapted decision making to prevent cancer therapy related cardiotoxicity. In recent years, momentous progress has been made toward the successful derivation of human cardiovascular cells from induced pluripotent stem cells (iPSCs). This technology has not only provided deeper mechanistic insights into basic cardiovascular biology but has also seamlessly integrated within the drug screening and discovery programs for early efficacy and safety evaluation. In this review, we discuss how iPSC-derived cardiovascular cells have been utilized for testing oncotherapeutics to pre-determine patient predisposition to cardiovascular toxicity. Lastly, we highlight the convergence of tissue engineering technologies and precision medicine that can enable patient-specific cardiotoxicity prognosis and treatment on a multi-organ level.

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion. Results In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending. [ABSTRACT FROM AUTHOR]

Background: Although the number of cancer clinical drug trials is increasing rapidly in China, issues concerning informed consent in this research context are understudied. By performing a narrative literature review, we aim to describe the current situation and identify the most salient challenges affecting informed consent in cancer clinical drug trials among adult patients in China since 2000. Methods: We searched Web of Science (WOS), PubMed, Scopus, EMBASE, the Cochrane Library databases, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database on Disc (CBMdisc), Chinese Scientific Journals Fulltext Database (CQVIP), and WANFANG Data to identify relevant publications since 2000. Data were extracted by three reviewers on six items pertaining to study type, theme, and challenges. Results: We identified 37 unique manuscripts, from which 19 full texts were obtained and six were included in the review. All six studies were published in Chinese journals, and the publication years of the majority (five out of six) of the studies were 2015 or later. The authors of the six studies were all from clinical departments or ethical review committees at five hospitals in China. All of the included publications were descriptive studies. Publications reported challenges related to the following aspects of informed consent: information disclosure, patient understanding, voluntariness, authorization, and procedural steps. Conclusion: Based on our analysis of publications over the past two decades, there are currently frequent challenges related to various aspects of informed consent in cancer clinical drug trials in China. Furthermore, only a limited number of high-quality research studies on informed consent in cancer clinical drug trials in China are available to date. Efforts toward improvement of informed consent practice, in the form of guidelines or further regulations in China, should draw on both experience from other countries and high-quality local evidence. [ABSTRACT FROM AUTHOR]

The drug dissociation constant (pKa) describes the ionization/protonation states. This physicochemical feature has a direct effect on the ADME properties of the active pharmacological compounds. In this study, using the LC method, the dependence of retention of tyrosine kinase inhibitors, erlotinib, canertinib, and bosutinib which are used in targeted therapy for several types of cancer, on the mobile phase pH was investigated at three different acetonitrile–water buffer compositions, and experimental data were utilized to calculate pKa values and capacity factors. Afterward, Yasuda–Shedlovsky extrapolation and mole fraction of acetonitrile plot used in order to acquire the pKa in aqueous medium. The observed results have been carefully compared to those reported in the literature that were obtained by different approaches. The conclusion is that these findings emphasize the potential of the physicochemical features of medications to aid in the comprehension of several biological systems, including human oral absorption, cell permeability, and protein binding in plasma. In addition, the pKa values of these ionizable molecules in various water–organic binary solutions are useful for the development of separation techniques focused on reversed-phase liquid chromatography and capillary electrophoresis. [ABSTRACT FROM AUTHOR]

Over recent years in China, the incidence and mortality of cancer have increased significantly, bringing a heavy economic burden on patients, patients' families and society. In this paper, we analyze main causes and heavy economic burden of cancer in China from aspects of disease characteristics and related social factors, and put forward suggestions on reducing the economic burden of cancer in China in the future.

Introduction/aims: There are disparities in the availability of systemic anticancer therapies (SACTs) globally. We set out to investigate the cost and reimbursement of SACTs in the United Kingdom (UK) and the Republic of Ireland (ROI) in conjunction with efficacy and licensing authority decisions in the United States (US) and the European Union (EU). Methods: We sought data pertaining to licensing in the EU, reimbursement in ROI/UK and cost/efficacy of SACTs licensed by the Food and Drug Administration (FDA) between January 2015 and May 2021. Independent samples t tests, chi-square test and Pearson's correlation were used for statistical analysis. Results: We identified that the majority of FDA-approved regimens are licensed by the European Medicines Agency (EMA) (n = 91, 67.9%). However, only a minority of these are currently reimbursed in the UK (n = 60, 45%) or the ROI (n = 28, 21%) as of the 1st of May 2021. In addition, only a minority of regimens have demonstrated a statistically significant OS benefit (n = 54, 40%). There was no association between cost of regimens and either the presence (t = 0.846, p = 0.40) or duration of OS benefit (t = − 0.84, p = 0.64). Conclusions: Our study highlights that many licensed systemic anticancer treatments are not currently reimbursed in ROI/UK. The high cost of these medicines is independent of the presence of an OS benefit. Collaboration between regulatory agencies, governments and industry partners is needed to ensure health expenditure is directed towards the most effective treatments. [ABSTRACT FROM AUTHOR]

Background: Litigation for health care, also known as health judicialization, is frequent in Brazil. It involves recourse to the court system to access health services. The study aimed to evaluate whether cancer patients in Belo Horizonte, Minas Gerais, Brazil, increased their overall survival by increasing access to certain drugs or treatments through litigation, controlling for the effect of demographic and disease-related variables. Methods: A retrospective cohort study was conducted. Patients with breast, prostate, brain, lung, or colon cancers from 2014 to 2019 were included. Survival analysis was performed using the Cox proportional hazards model. Results: In the multivariate analysis, litigation was significantly associated with increased survival in cancers of breast (HR = 0.51, 95%CI 0.33–0.80), prostate (HR = 0.50, 95%CI 0.30–0.85), colon (HR = 0.59, 95%CI 0.38–0.93), and lung (HR = 0.36, 95%CI 0.22–0.60). Five-year survival rates of patients who sued for treatment were 97.8%, 88.7%, 59.3%, and 26.0%, compared to median survival of 95.7%, 78.7%, 41.2%, and 2.4%, respectively, among patient that did not resort to court action. The study suggests that litigation for access to cancer treatment may represent a step forward in obtaining more effective treatment. This study´s main limitations are the lack of patients´ clinical information for use as control variables and the lack of variables to assess patients´ quality of life. The study also found that many cases involved claims that could have been solved by administrative rather than legal action. Some claims thus reflect the lack of adequate administrative procedures. Conclusion: When based on scientific evidence, access to new therapies, combined with other technologies already available, can favor patient survival. Access to new therapies through litigation may increase health inequalities since low-income patients have limited access to legal recourse against the State to meet their needs. The timely approval of new effective therapies can mitigate the judicialization of cancer treatment. [ABSTRACT FROM AUTHOR]

Rapid increase in cost continues to have negative impact on patients’ accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a university hospital to tackle this imbalance and strive to provide high quality, sustainable, affordable and accessible care. An active approach in cost containment of expensive and innovative cancer drugs was adopted in our organisation to safeguard accessibility and improve quality of life for patients. In this article, we described four inverventions: 1) identify right patient and minimise overtreatment, 2) in-house medicine production for selected indications, 3) minimise medicine spillages and 4) effective procurement strategies. We call on other hospitals to take action and, favourably, to collaborate on a European level. Together, we will safeguard the current and future care of our patients.

Summary: Background: Access to essential cancer medicines is a key determinant of childhood cancer survival. WHO published the Model List of Essential Medicine for Children (EMLc) and updated it every two years since 2007 to promote better access to medicines for children. This study aimed to assess whether the inclusion of essential anticancer medicines for respective indications for children was based on evidence of significant clinical benefit between 2011 and 2021. Methods: We identified all anticancer medicine indications added to the WHO EMLc Section 8 since 2011 and extracted evidence of benefit documented in the corresponding technical reports. Evidence in children was defined as evidence that included participants under 12, and graded into five levels, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. We analyzed whether each anticancer medicine indication was listed with documented OS benefit or improvements in surrogate measures based on the highest level of documented evidence in children. Findings: A total of 115 anticancer medicine indications were added to the EMLc from 2011 to 2021, of which 101 (87.8%) had some clinical evidence in children and 4 (3.5%) were added without any clinical evidence. Among the 101 medicine indications, none were added with level-1 evidence in children, and 43 (42.6%), 11 (10.9%), 41 (40.6%), and 6 (5.9%) were listed with level-2, level-3, level-4, and level-5 evidence in children, respectively. Only eight (7.9%) medicine indications were reported to have OS benefit, another 12 (11.9%) were reported to have improvements on surrogate measures, and 81 (80.2%) were listed in the EMLc without documented improvements in either OS or surrogate measures. Interpretation: Most anticancer medicine indications of the WHO EMLc were added based on limited evidence of statistically significant clinical benefit in children. Our results suggest that WHO should refine requirements for clinical benefit criteria and permissible forms, quality, and reporting of evidence of essential anticancer medicines for children, specify whether anticancer medicine indications have required evidence of clinical benefit in children, and provide further details in its technical reports that summarise the available evidence. Funding: Not applicable.

Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces (except Quebec), which each then decide whether the drug will be publicly funded. We identified the determinants of funding in this process. Methods: We analyzed drugs for advanced lung (n = 15), breast (n = 8), colorectal (CRC) (n = 7), melanoma (n = 10), and neuroendocrine (NET) (n = 3) cancers undergoing the funding decision process from 2011 to 2019. Determinants of funding assessed in the model included list price, cancer type, drug class, and pCODR recommendation. The primary outcome was the correlation between list price and time to funding (TTF: Health Canada approval to first provincial funding). Secondary outcomes included an exploratory analysis of predictors of drug funding. Results: We analyzed 43 drugs: targeted agents 72%, immunotherapy 20%, chemotherapy 7%. A total of 72% were funded in at least one province. Median TTF was 379 days (IQR 203–601). Median list price (28-day course) was CAD 8213 (IQR CAD 5391–9445). Higher list price was not correlated with TTF (correlation coefficient −0.20, p = 0.28). There was no association between list price and pCODR recommendation or the decision to fund in at least one province. A positive pCODR recommendation correlated with the provinces’ funding decisions (p < 0.001), where 89% of drugs with a positive recommendation were funded and 100% of drugs with a negative recommendation were not funded. Tumor type was predictive of TTF (p < 0.001): CRC drugs were the slowest at a median of 2541 days (IQR 702–4379), and NETs were the quickest at a median of 0 days (IQR 0–502). Cancer type predicted decision to fund in at least one province (p = 0.005), with funding for 100% of NET drugs at the high end and 29% of CRC drugs at the low end. Drug class was predictive of TTF (p = 0.01): 465 days (IQR 245–702) for targeted agents, 443 days (IQR 298–587) for chemotherapy, and 339 days (IQR 164–446) for immunotherapy. Conclusions: Determinants of drug funding included cancer type, drug class, and pCODR recommendation but not list price. Factors other than cost were more heavily weighted in the funding decisions of cancer drugs in Canadian provinces.

Cellular phenotypes of apoptosis, as well as the activation of apoptosis caspase cascades, are well described. However, sequences and locations of early biochemical effector events after apoptosis initiation are still only partly understood. Here, we use integrated modulation of protein interaction states-cellular thermal shift assay (IMPRINTS-CETSA) to dissect the cellular biochemistry of early stages of apoptosis at the systems level. Using 5 families of cancer drugs and a new CETSA-based method to monitor the cleavage of caspase targets, we discover the initial biochemistry of the effector stage of apoptosis for all the studied drugs being focused on the peripheral nuclear region rather than the cytosol. Despite very different candidate apoptosis-inducing mechanisms of the drug families, as revealed by the CETSA data, they converge into related biochemical modulations in the peripheral nuclear region. This implies a higher control of the localization of the caspase cascades than previously anticipated and highlights the nuclear periphery as a critical vulnerability for cancer therapies. [Display omitted] • IMPRINTS-CETSA reveals drug-specific and converging mechanisms of apoptotic drugs • The initial effector phase of apoptosis is focused on the peripheral nuclear region • Regional stabilization after proteolysis (RESP) identifies proteolytic events in living cells IMPRINTS-CETSA reveals that apoptosis-inducing drugs with distinct mechanisms converge into biochemical modulations in the peripheral nuclear region. We were able to identify proteolytic events in living cells by a phenomenon we call regional stabilization after proteolysis (RESP), where specific parts of the protein get stabilized. [ABSTRACT FROM AUTHOR]

A disease caused by cellular alterations that is unrestrained cell growth and division is cancer. Many anticancer medications, including those used to treat blood, breast, and skin cancer, may have their physical, chemical, and biological features predicted. This paper presents novel distance-based topological indices (TIs) computed using the suggested KP-polynomial with blood cancer drugs. The objective of the QSPR investigation is to determine the mathematical correlation between the analyzed properties (such as Molar Volume, Refractive Index, etc.) and different descriptors associated with the molecular structure of the medications. A polynomial regression model is employed to assess the predictive capability of TIs. The results are represented using a correlation coefficient to establish the connection between the predicted and observed values of blood cancer drugs. This theoretical method could potentially enable chemists and health care professionals to anticipate the characteristics of blood cancer drugs without the need for actual experimental tests. This leads towards new opportunities to paved the way for drug discovery and the formation of efficient multicriteria decision making technique TOPSIS for ranking of said disease treatment drugs and physicochemical characteristics. [ABSTRACT FROM AUTHOR]

Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development and spending, it is crucial to have an understanding of the processes and pressures new drugs navigate to get to the market in Canada. This paper is a review of the complex, multi-step regulatory and funding process undertaken by cancer drugs in Canada. It reviews the role of Health Canada, the Patented Medicine Prices Review Board, the Health Technology Assessment, the pan-Canadian Pharmaceutical Alliance, and finally, the provincial, territorial, and federal payers. Recent developments are highlighted. Strategies to minimize duplication of effort, improve timeliness, and increase efficiency are explored. The cancer drug regulatory and funding process in Canada is complex, and an understanding of the current system and ongoing evolution is essential.

BackgroundWhether the high cost of cancer drugs is commensurate with their value to patients, which has become the focus of public concern. We aimed to assess the value of new cancer drugs approved for solid cancer in China and to explore the association between price and value of drugs.MethodsWe identified all new drugs for solid tumor that approved by the China's National Medical Products Administration (NMPA) between 2016 and 2020. The value of these drugs was assessed according to the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Cohen's κ statistic to describe agreement between the two frameworks. Spearman's correlation coefficient was used to evaluate the correlation between price and value of drugs.ResultsBetween 2016 and 2020, 37 new drugs were approved by the NMPA for solid tumor and we could evaluate the value of 28 drugs (76%). Eight (29%) of drugs were approved for non-small-cell lung cancer and 6 (21%) for breast cancer. ASCO-VF scores had a range of −20 to 110.1, and the median score was 43.3 (inter-quartile range 27.1–58.35). Only seven drugs (25%) met the ASCO-VF cutoff score. By the ESMO-MCBS, 13 drugs showed a meaningful value. Agreement between these two frameworks thresholds was only fair (κ = 0.515, P < 0.05). We found no statistically significant correlation between launch price of drugs and clinical benefit according to both frameworks.ConclusionsNot all NMPA-approved new cancer drugs had meaningful value as measured by ASCO-VF or ESMO-MCBS. There was no significant correlation between drug price and the level of clinical benefit.

Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges. [ABSTRACT FROM AUTHOR]

Nanotechnology has a versatile use in the field of disease therapy, targeted drug delivery, biosensing, and environmental protection. The cross-linked nanosponges are one of the types of nanostructures that provide huge application in the biomedical field. They are available up to the fourth generation and can act as a payload for both kinds of hydrophilic and hydrophobic drugs. There are different methods available for the synthesis of these nanosponges as well as loading the drugs inside them. A variety of approved drugs based on nanosponges are already in the market including drugs for cancer. Other applications include the uses of nanosponges as topical agent, in improving solubility, as protein carrier, in chemical sensors, in wastewater remediation, and in agriculture. The present review discusses in detail about different applications of nanosponges and also mentions about the recent SARS-CoV-2 management using nanosponges. [ABSTRACT FROM AUTHOR]

Objectives: To quantify the strength of statistical evidence of randomized controlled trials (RCTs) for novel cancer drugs approved by the Food and Drug Administration in the last 2 decades., Study Design and Setting: We used data on overall survival (OS), progression-free survival, and tumor response for novel cancer drugs approved for the first time by the Food and Drug Administration between January 2000 and December 2020. We assessed strength of statistical evidence by calculating Bayes factors (BFs) for all available endpoints, and we pooled evidence using Bayesian fixed-effect meta-analysis for indications approved based on 2 RCTs. Strength of statistical evidence was compared among endpoints, approval pathways, lines of treatment, and types of cancer., Results: We analysed the available data from 82 RCTs corresponding to 68 indications supported by a single RCT and 7 indications supported by 2 RCTs. Median strength of statistical evidence was ambiguous for OS (BF = 1.9; interquartile range [IQR] 0.5-14.5), and strong for progression-free survival (BF = 24,767.8; IQR 109.0-7.3 × 10 6 ) and tumor response (BF = 113.9; IQR 3.0-547,100). Overall, 44 indications (58.7%) were approved without clear statistical evidence for OS improvements and 7 indications (9.3%) were approved without statistical evidence for improvements on any endpoint. Strength of statistical evidence was lower for accelerated approval compared to nonaccelerated approval across all 3 endpoints. No meaningful differences were observed for line of treatment and cancer type. This analysis is limited to statistical evidence. We did not consider nonstatistical factors (eg, risk of bias, quality of the evidence)., Conclusion: BFs offer novel insights into the strength of statistical evidence underlying cancer drug approvals. Most novel cancer drugs lack strong statistical evidence that they improve OS, and a few lack statistical evidence for efficacy altogether. These cases require a transparent and clear explanation. When evidence is ambiguous, additional postmarketing trials could reduce uncertainty., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To systematically review published evidence on cancer drug wastage and the effectiveness of mitigation methods., Methods: Search keywords for Scopus, PubMed, and EMBASE were developed using the Pearl Growing technique. Relevant articles were identified in a two-step process: first based on titles/abstracts, then on full article reviews. Among the identified English peer-reviewed articles, those considering adults ≥18 years and relevant cancer drug wastage outcomes were included. Key concepts and measures for drug wastage and its mitigation were tabulated. Trends in publication numbers were analyzed using Mann-Kendall tests. Costs were converted first to 2024 local currencies using country-wise consumer price indexes, and then to 2024 USD using exchange rates., Results: Among 6,298 unique articles, 94 met the inclusion criteria. Seventy-four (79%) of these were published since 2015, highlighting increasing attention to cancer drug wastage. Twenty-three articles (24%) explicitly reported drug wastage amounts, whereas fifty-two articles (55%) considered the mitigation methods. Most articles focused on high-income countries (n=67), single hospital settings (n=45), and retrospective study designs (n=55). Wastage mitigation techniques included vial-sharing (n=21), dose-rounding (n=17), closed-system transfer device (n=9), centralized drug preparation (n=7), and vial size optimization (n=7). A trend towards higher median wastage cost was evident in US settings ($135.35/patient-month) compared to other countries ($37.71/patient-month)), while mitigation methods across countries were not statistically significant., Conclusions: High cancer drug costs highlight the importance of minimizing drug wastage to reduce healthcare expenditure. Our review demonstrates that wastage varies by healthcare setting and mitigation technique. Future studies would benefit from reporting standards for cancer drug wastage that include reporting wastage (both in mg and cost, preferably in terms of Purchase Power Parity), as well as cohort size, considered vial sizes, considered dosages, and employed mitigation methods separately for each drug. This approach would account for variability in cancer drug wastage and help identify optimal mitigation practices tailored to the health system context., (Copyright © 2024. Published by Elsevier Inc.)

Abstract Background As the range of therapeutic options in the field of oncology increases, so too does the strain on health care budgets. The imbalance between what is medically possible and financially feasible is frequently rendered as an issue of tragic choices, giving rise to public controversies around health care rationing. Main body We analyse the Norwegian media discourse on expensive cancer drugs and identify four underlying premises: (1) Cancer drugs are de facto expensive, and one does not and should not question why. (2) Cancer drugs have an indubitable efficacy. (3) Any lifetime gained for a cancer patient is an absolute good, and (4) cancer patients and doctors own the truth about cancer. Applying a principle-based approach, we argue that these premises should be challenged on moral grounds. Within the Norwegian public discourse, however, the premises largely remain unchallenged due to what we find to be unjustified claims of moral superiority. We therefore explore alternative framings of the issue of expensive cancer drugs and discuss their potential to escape the predicament of tragic choices. Conclusions In a media discourse that has seemingly stagnated, awareness of the framings within it is necessary in order to challenge the current tragic choices predicament the discourse finds itself in. In order to allow for a discourse not solely concerned with the issue of tragic choices, the premises that underlie it must be subjected to critical examination. As the field of oncology advances rapidly, we depend on a discussion of its opportunities and challenges that is meaningful, and that soberly addresses the future of cancer care—both its potential and its limits.

Summary: Background. Previous research focused on the clinical evidence supporting new cancer drugs' initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit. Objectives. To examine the clinical trial evidence supporting new targeted cancer drugs' initial and supplementary indication approval in the US, EU, Canada, and Australia. Data and Methods. 25 cancer drugs across 100 indications were identified with FDA approval between 2009–2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI). Results. Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07–6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38–8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17–5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14–30.65], p < 0.05) than supplementary indications. Initial indications' pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93–0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09–0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01–1.39], p < 0.05). Conclusions. Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication's differential clinical and economic value. [ABSTRACT FROM AUTHOR]

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2022 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2022 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2022 were based on a combination of quantitative analyses and expert opinion. Results In 2021, overall pharmaceutical expenditures in the US grew 7.7% compared to 2020, for a total of $576.9 billion. Utilization (a 4.8% increase), price (a 1.9% increase) and new drugs (a 1.1% increase) drove this increase. Adalimumab was the top drug in terms of overall expenditures in 2021, followed by apixaban and dulaglutide. Drug expenditures were $39.6 billion (a 8.4% increase) and $105.0 billion (a 7.7% increase) in nonfederal hospitals and in clinics, respectively. In clinics and hospitals, new products and increased utilization growth drove growth, with decreasing prices for both sectors acting as an expense restraint. Several new drugs that are likely to influence spending are expected to be approved in 2022. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2022, we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 7.0% to 9.0% and 3.0% to 5.0%, respectively, compared to 2021. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending. [ABSTRACT FROM AUTHOR]

The term “molecular ZIP (or area) codes” refers to an originally hypothetical system of cell adhesion molecules that would control cell trafficking in the body. Subsequent discovery of the integrins, cadherins, and other cell adhesion molecules confirmed this hypothesis. The recognition system encompassing integrins and their ligands came particularly close to fulfilling the original ZIP code hypothesis, as multiple integrins with closely related specificities mediate cell adhesion by binding to an RGD or related sequence in various extracellular matrix proteins. Diseased tissues have their own molecular addresses that, although not necessarily involved in cell trafficking, can be made use of in targeted drug delivery. This article discusses the molecular basis of ZIP codes and the extensive effort under way to harness themfor drug delivery purposes. [ABSTRACT FROM AUTHOR]

Chitin and its derivative chitosan are highly abundant polymers in nature, appearing in both the shells and exoskeletons of various marine and non-marine species. Since they possess favorable properties, such as biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, they have gained recent attention due to their enormous potential biomedical applications. The polycationic surface of chitosan enables it to form hydrogenic and ionic bonds with drug molecules, which is one of its most useful properties. Because chitosan is biocompatible, it can therefore be used in drug delivery systems. The development of chitosan-based nanoparticles has also contributed to the significance of chitin as a drug delivery system that can deliver drugs topically. Furthermore, chitin can be used in cancer treatment as a vehicle for delivering cancer drugs to a specific site and has an antiproliferative effect by reducing the viability of cells. Finally, chitosan can be used as a wound dressing in order to promote the faster regeneration of skin epithelial cells and collagen production by fibroblasts. As discussed in this review, chitin and chitosan have diverse applications in the medical field. Recognizing the biomedical applications of these two polymers is essential for future research in tissue engineering and nanobiotechnology. [ABSTRACT FROM AUTHOR]

Summary: Introduction We analyzed the outcomes of patients with advanced cancers in our institution treated with off-label drugs targeting actionable genomic alteration based on next-generation sequencing who did not qualify for clinical trials. Purposes Our study endpoint was objective tumor response or stable disease at 16 weeks or later after treatment initiation. Methods Sixteen patients were included, 8 treated with immune checkpoint inhibitors targeting PD-L1 expression or TP53 mutations and 8 with other drugs. Tumors were analyzed based on PD-L1 expression, TP53 mutation, MSI, TMB, MMR status, and other targetable alterations. Results Of the 16 patients in the intention-to-treat group, no patients had an objective response after 16 weeks. Eleven patients met the primary study endpoint with stable disease, 8 in the immune checkpoint inhibitors group and 3 in the non-immune checkpoint inhibitors group. Using the log-rank test, the p-value for the difference between groups was 0.008. Conclusions In this study with off-label drugs, immune checkpoint inhibitors targeting TP53 mutations or PD-L1 expression were superior to the other drugs. This suggests the possibility of off-label use of anti-cancer drugs based on next-generation sequencing to be beneficial for advanced cancer patients without other therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Imidazole nucleus has been used efficiently in the development of many drug molecules due to its therapeutic effects. Many derivatives of it have been produced particularly for use in cancer treatment. However, the anti-cancer effects of imidazole nucleus in liver cancer cells are as yet unclear. In this study, we aimed to investigate the anti-cancer effects of imidazole nucleus in hepatocellular carcinoma (HCC) cell lines. Methods and results: Anti-cancer effect of imidazole nucleus was investigated using cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques in HuH-7 and Mahlavu cell lines. Also, effect of imidazole on AKT and ERK1/2 pathways were determined using by western blot analysis. Imidazole decreased cell viability in both HCC cell lines in a dose and time-dependent manner and also suppressed the colony forming ability of the cells (p < 0.05). Imidazole increased the cleaved caspase 3 protein levels and thus induced apoptosis (p < 0.05). Imidazole induced morphological alterations and autophagy by increasing intracellular vacuolization. Also, imidazole decreased the viability and dimensions of HCC cell tumor spheroids produced in 3D cell cultures (p < 0.05). Moreover, it was observed that all of these effects, are defined above, appeared in parallel with suppression of AKT and ERK1/2 signaling pathways by imidazole nucleus. Conclusions: The findings of this present study established the anti-cancer effects of imidazole nucleus in HCC cell lines and showed that it could be a potential molecule in the treatment of HCC via inhibition of AKT and ERK1/2 signaling pathways. [ABSTRACT FROM AUTHOR]