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The next frontier in anti-cancer drugs
Dr Anthony J. Berdis, Case Comprehensive Cancer Center discusses the future of cancer treatments and anti-cancer drugs. Being diagnosed with cancer is a horrifying experience for patients and their loved ones. What comes next – discussing treatment strategies – can also strike terror due to the numerous uncertainties associated with the process, procedures that will be used, and possible outcomes. Most cancers are treated using combination therapy in which surgery and/or radiation is first used to remove and eliminate as much cancerous material as possible. This is then followed by several rounds of chemotherapy, an anti-cancer drug designed to eradicate any remaining cancer cells. The goal of this strategy is to achieve remission or at least delay the cancer from returning for as long as possible.

Review.-- Creative Commons Attribution Non-Commercial No-Derivatives License. ; Cancer is the subject of intense research around the world, but many questions about how the disease works remain unanswered. How exactly does cancer start and how do tumours grow? In fact, at present there are ten times more anticancer drugs being tested in clinical trials than there were 15 years ago. However, many of the new anticancer agents are predicted to show clinical benefit in only small subpopulations of patients. The cancer stem cell model could explain not only how some cancers work but also why patients suffer relapses, providing a good opportunity to gain insight into the reasons why agents work or, more commonly, don't work, before going into a clinical trial. ; Research in ISG group was partially supported by FEDER and by MICINN (SAF2009-08803 to ISG), by Junta de Castilla y León (REF. CSI007A11-2 and Proyecto Biomedicina 2009-2010 to ISG), by MEC OncoBIO Consolider-Ingenio 2010 (Ref. CSD2007-0017), by NIH grant (R01 CA109335-04A1), by Sandra Ibarra Foundation, by Group of Excellence Grant (GR15) from Junta de Castilla y Leon, and the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program) and by proyecto en red de investigación en celulas madre tumorales en cancer de mama supported by Obra Social Kutxa y Conserjería de Sanidad de la Junta de Castilla y Leon. All Spanish funding is co-sponsored by the European Union FEDER program. ISG is an API lab of the EuroSyStem project. J. Pérez-Losada is partially supported by FEDER and MICINN (PLE2009-119), FIS (PI10/00328), Fundación Eugenio Rodríguez Pascual, Fundación Inbiomed, Instituto Oncológico, Obra Social de la Caja Guipozkoa-San Sebastián (Kutxa). A. Castellanos-Martín is supported by FEDER and MICINN (PLE2009-119). ; Peer Reviewed

Abstract Peru's first cancer control public outreach scheme started in the 1910s, but ground to a standstill as it attained official governmental recognition in 1926 as the Liga Anti-Cancerosa (LAC). This paper explains the developments leading to that earliest effort to enlist a coalition of State health agencies, physicians, and lay people in a campaign to publicize early signs of this disease, as well as the medical and political reasons for and implications of its decline. Besides highlighting the importance of professional initiatives shaping cancer activism, contextualizing the rise and fall of the LAC calls attention to the effects that hospitalization of cancer treatment had on aspects of cancer care that were not directly treatment-related, such as public outreach.

In recent years, a lot of scientific interest has focused on cancer immunotherapy. Although chronic inflammation has been described as one of the hallmarks of cancer, acute inflammation can actually trigger the immune system to fight diseases, including cancer. Toll-like receptor (TLR) ligands have long been used as adjuvants for traditional vaccines and it seems they may also play a role enhancing efficiency of tumor immunotherapy. The aim of this perspective is to discuss the effects of TLR stimulation in cancer, expression of various TLRs in different types of tumors, and finally the role of TLRs in anti-cancer immunity and tumor rejection. Copyright 2019 The Authors. ; This work was supported in part by the Intramural Research Program of NIAID, NIH, National Institutes of Health 1R01AI123820-01 (DG), and the International Centre for Cancer Vaccine Science project of the International Research Agendas program of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund (MAB/2017/03) at the University of Gdansk (ZU-W, NM-T, RF, DG, and TH). ; https://doi.org/10.3389/fimmu.2019.02388

Background The Systemic Anti-Cancer Therapy (SACT) dataset is a unique source of national, real-world data reporting chemotherapy activity delivered by NHS treatment providers in England. SACT data are collected with the intent of improving disease-free or progression-free survival.
Main Aim The SACT dataset aims to provide a detailed resource on systemic treatments delivered in secondary and tertiary settings in England for patients with cancer.
Approach The SACT dataset is collected and curated by the National Cancer Registration and Analysis Service (NCRAS) at Public Health England. The dataset was launched in a phased implementation from April 2012. From April 2014 submission of SACT data became mandatory for all NHS treatment providers. Data are collected on the patient, tumour, regimen, treatment cycle, drug details, and treatment outcomes. The SACT dataset can be linked to other data held by NCRAS, for example the cancer registry1, Hospital Episodes Statistics2, and the national Radiotherapy Dataset to provide a complete picture of the cancer patient pathway.
Results The SACT dataset is being used: for the appraisal of drugs funded through the Cancer Drugs Fund; to review the quality of cancer care as part of the National Cancer Audits; and for observational research purposes, including investigating 30-day mortality following chemotherapy3, and sociodemographic variation in the use of chemotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer4. The data are also released to external researchers via the Office for Data Release.
Conclusion The SACT dataset is a unique resource in terms of the breadth and depth of information on chemotherapy prescribed to cancer patients. The key strengths are: the national coverage; real-world data; detailed clinical information beyond cancer registration data; and the ability to link to other cancer datasets.
References

Henson KE, Elliss-Brookes L, Coupland VH, Payne E, Vernon S, Rous B et al. Data Resource Profile: National Cancer Registration Dataset in England. Int J Epidemiol 2019; doi 10.1093/ije/dyz076.
Herbert A, Wijlaars L, Zylbersztejn A, Cromwell D, Hardelid P. Data Resource Profile: Hospital Episode Statistics Admitted Patient Care (HES APC). Int J Epidemiol 2017; 46(4): 1093-1093i; e-pub ahead of print 2017/03/25; doi 10.1093/ije/dyx015.
Wallington M, Saxon EB, Bomb M, Smittenaar R, Wickenden M, McPhail S et al. 30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study. The Lancet Oncology 2016; 17(9): 1203-1216; doi 10.1016/s1470-2045(16)30383-7.
Henson KE, Fry A, Lyratzopoulos G, Peake M, Roberts KJ, McPhail S. Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013-2014. Br J Cancer 2018; doi 10.1038/s41416-018-0028-7.

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step. Copyright: ; SCOPUS: ar.j ; info:eu-repo/semantics/published

Abstract Background Reimbursement policies for anti-cancer drugs vary among countries even though they rely on the same clinical evidence. We compared the pattern of publicly funded drug programs and analyzed major factors influencing the differences. Methods We investigated reimbursement policies for 19 indications with targeted anti-cancer drugs that are used variably across ten countries. The available incremental cost-effectiveness ratio (ICER) data were retrieved for each indication. Based on the comparison between actual reimbursement decisions and the ICERs, we formulated a reimbursement adequacy index (RAI): calculating the proportion of cost-effective decisions, either reimbursement of cost-effective indications or non-reimbursement of cost-ineffective indications, out of the total number of indications for each country. The relationship between RAI and other indices were analyzed, including governmental dependency on health technology assessment, as well as other parameters for health expenditure. All the data used in this study were gathered from sources publicly available online. Results Japan and France were the most likely to reimburse indications (16/19), whereas Sweden and the United Kingdom were the least likely to reimburse them (5/19 and 6/19, respectively). Indications with high cost-effectiveness values were more likely to be reimbursed (ρ = −0.68, P = 0.001). The three countries with high RAI scores each had a healthcare system that was financed by general taxation. Conclusions Although reimbursement policies for anti-cancer drugs vary among countries, we found a strong correlation of reimbursements for those indications with lower ICERs. Countries with healthcare systems financed by general taxation demonstrated greater cost-effectiveness as evidenced by reimbursement decisions of anti-cancer drugs.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. ; Background: Reimbursement policies for anti-cancer drugs vary among countries even though they rely on the same clinical evidence. We compared the pattern of publicly funded drug programs and analyzed major factors influencing the differences. Methods: We investigated reimbursement policies for 19 indications with targeted anti-cancer drugs that are used variably across ten countries. The available incremental cost-effectiveness ratio (ICER) data were retrieved for each indication. Based on the comparison between actual reimbursement decisions and the ICERs, we formulated a reimbursement adequacy index (RAI): calculating the proportion of cost-effective decisions, either reimbursement of cost-effective indications or non-reimbursement of cost-ineffective indications, out of the total number of indications for each country. The relationship between RAI and other indices were analyzed, including governmental dependency on health technology assessment, as well as other parameters for health expenditure. All the data used in this study were gathered from sources publicly available online. Results: Japan and France were the most likely to reimburse indications (16/19), whereas Sweden and the United Kingdom were the least likely to reimburse them (5/19 and 6/19, respectively). Indications with high cost-effectiveness values were more likely to be reimbursed (ρ = −0.68, P = 0.001). The three countries with high RAI scores each had a healthcare system that was financed by general taxation. Conclusions: Although reimbursement policies for anti-cancer drugs vary among countries, we found a strong correlation of reimbursements for those indications with lower ICERs. Countries with healthcare systems financed by general taxation demonstrated greater cost-effectiveness as evidenced by reimbursement decisions of anti-cancer drugs. ; Peer Reviewed

BACKGROUND: To reduce out‐of‐pocket costs, the Korean government expanded health insurance reimbursement in anti‐cancer drugs for cancer patients in 2013. Our objective was to examine the impact of the benefit coverage expansion policy on healthcare utilization and overall survival (OS) among patients with six types of solid cancer after the policy of expanding health insurance coverage. METHODS: This study analyzed a before‐and‐after retrospective cohort of patients newly diagnosed with six types of solid cancer (stomach cancer, colorectal cancer, lung cancer, liver cancer, breast cancer, and prostate cancer) from January 1, 2009 to December 31, 2015 in Korea. The intervention was the expansion of reimbursement in 2013. Multivariate Cox proportional hazards regression was used to estimate the policy effect. RESULTS: In total, 142,579 before and 147,760 patients after the benefit expansion, and after matched by age, gender, and stage, 132,440 before and 132,440 patients after policy were included in the analysis. Almost total medical expenditure increased for five types of cancer increased. The expansion of health insurance reimbursement was associated with significantly lower overall mortality compared with pre‐policy mortality for all six cancer sites. CONCLUSION: The policy of expanding health insurance reimbursement might have been associated with a significant increase in survival among cancer patients by ensuring access to health care and medicine. Although the reimbursement expansion timing differs for each cancer, it is believed that eliminating delayed treatment might rather lead to reduce medical expenses and improve health outcomes.

Background: The aim of this study was to examine the access of Indian cancer patients to optimum cancer care under selected government schemes by reviewing reimbursement schemes for cancer care in India.Methods: All cancer care reimbursement schemes in India were identified and three highly utilized schemes (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head & neck, and gastric cancer care was reviewed with respect to NCCN guidelines. Direct medical costs and shortage of budget in reimbursed amounts were calculated for each listed chemotherapy regimen.Results: Medical oncology practice following the schemes' formularies is inferior to recommendations by the NCCN guidelines. Innovative treatment (targeted therapies) like trastuzumab, pertuzumab (breast), bevacizumab, cetuximab, panitumumab (colorectal), erlotinib, gefitinib, crizotinib, and nivolumab (lung) are either not reimbursed (VAS, CMCHS) or partially reimbursed (RAS). Average shortage of budget was found to be 43% (breast), 55% (colorectal), 74% (lung), 7% (head & neck), and 51% (gastric cancer).Conclusions: Policy makers should consider addition of newer treatments, exclusion of sub-optimal treatments, increments in per patient budget and optimization of supportive care, which may contribute to improvements in survival and quality of life for Indian cancer patients.

Cancer is awful disease, which makes panicle network in the body system of patients. Cancer is characterized by abnormal and uncontrolled cell growth, which results in the formation of lumps or masses in body known as tumor. There are more than 100 types of cancers and each is classified according to the cell capacity and size. Globally, cancer is accepted as the second leading cause of death. As per a WHO report, cancer is responsible for 8.8 million deaths in 2015. Anti-cancer drugs or oncology medicines are employed in taking the care of different patients. At the present time, many pharmaceutical companies are active in producing oncology medicines. It is probed that by pharmaceutical scientists how cancer treatments under the scheduled time can save life of patients and a delay in treating cancer patients may have unseemly effects on the life of patients. The presented research focuses on two cases. The first was conducted at Jabalpur Hospital & Research Centre (JHRC), where a structure/model related to A-CMsP company is built for assessing the performance under chain of sustainable procurement criteria. The second research focuses on the benchmarking of two A-CMsP companies. A multi objective optimization approach is implemented, accompanied with vague modeling for computing the overall performance index of oncology medicines.

The aim of this study was to examine the access of Indian cancer patients to optimum cancer care under selected government schemes by reviewing reimbursement schemes for cancer care in India.Methods: All cancer care reimbursement schemes in India were identified and three highly utilized schemes (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head & neck, and gastric cancer care was reviewed with respect to NCCN guidelines. Direct medical costs and shortage of budget in reimbursed amounts were calculated for each listed chemotherapy regimen.Results: Medical oncology practice following the schemes' formularies is inferior to recommendations by the NCCN guidelines. Innovative treatment (targeted therapies) like trastuzumab, pertuzumab (breast), bevacizumab, cetuximab, panitumumab (colorectal), erlotinib, gefitinib, crizotinib, and nivolumab (lung) are either not reimbursed (VAS, CMCHS) or partially reimbursed (RAS). Average shortage of budget was found to be 43% (breast), 55% (colorectal), 74% (lung), 7% (head & neck), and 51% (gastric cancer).Conclusions: Policy makers should consider addition of newer treatments, exclusion of sub-optimal treatments, increments in per patient budget and optimization of supportive care, which may contribute to improvements in survival and quality of life for Indian cancer patients.