[This corrects the article DOI: 10.1155/2021/9996193.].

Background: Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care. This can support policy decisions including funding. Consequently, there is a need for improving datasets for establishing real-world outcomes of newly launched oncology medicines. Aim: To outline the types of available datasets for collecting patient-level data for oncology among different European countries. Additionally, to highlight concerns regarding the use and availability of such data from a health authority perspective as well as possibilities for cross-national collaboration to improve data collection and inform decision-making. Methods: A mixed methods approach was undertaken through a cross-sectional questionnaire followed-up by a focus group discussion. Participants were selected by purposive sampling to represent stakeholders across different European countries and healthcare settings. Descriptive statistics were used to analyze quantifiable questions, whilst content analysis was employed for open-ended questions. Results: 25 respondents across 18 European countries provided their insights on the types of datasets collecting oncology data, including hospital records, cancer, prescription and medicine registers. The most available is expenditure data whilst data concerning effectiveness, safety and outcomes is less available, and there are concerns with data validity. A major constraint to data collection is the lack of comprehensive registries and limited data on effectiveness, safety and outcomes of new medicines. Data ownership limits data accessibility as well as possibilities for linkage, and data collection is time-consuming, necessitating dedicated staff and better systems to facilitate the process. Cross-national collaboration is challenging but the engagement of multiple stakeholders is a key step to reach common goals through research. Conclusion: This study acts as a starting point for future research on patient-level databases for oncology across Europe. Future recommendations will require continued engagement in research, building on current initiatives and involving multiple stakeholders to establish guidelines and commitments for transparency and data sharing.

The use of the biological medicines, also called “biologics,” has contributed to the progress of the treatment of many chronic diseases, such as cancer, rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and psoriasis. However, biologicals are expensive for healthcare systems in several countries. Their availability has been a global issue, which has affected many patients that suffer from various diseases. A biosimilar medicine, also called “biosimilar,” is a medicine with similar characteristics in terms of quality, biological activity, safety, and efficacy as the approved original biological medicine, known as “originator biologic.” Biosimilars generate competition within the market because they lower the prices of biologics and thus allow for an increase in patient access. However, there are barriers when it comes to the acceptability rate of biosimilars and how interchangeable they are with the originator biologic. In this review, we present a national regulatory framework for biologics along with its limitations, a system of monitoring the safety profile of biologics, the guideline for interchangeability, and a list of approved and available biologics in Bosnia and Herzegovina. Additionally, recommendations were made here in order to provide opportunities for greater acceptance of biosimilars and better access to biologics. These recommendations include, but are not limited to, strengthening the national regulatory framework for biologics, capacity building, increasing awareness among healthcare providers for reporting adverse drug events and active pharmacovigilance, and better definitions of interchangeability. Finally, awareness among healthcare providers regarding biosimilars and biologics should be raised through continuous education and workshops, and by including this important topic in the graduate and postgraduate curriculum programs in the country.

Background / Aim: Up until ten years ago stage four melanoma was considered a disease with extremely poor prognosis. Standard therapy during this period of time was dacarbazine chemotherapy. Patients with better performance status were treated with immunotherapy cytokine IL-2. In the last ten years eight medications have been approved by the FDA for the therapy of melanoma. The goal of this study was to determine objective response rate (ORR), median overall survival (OS), median progression free survival (PFS) and safety in patients with advanced and metastatic cutaneous melanoma treated with targeted therapy and immunotherapy at the University Clinical Centre of the Republic of Srpska (Centre). Methods: A non-randomised observational retrospective/prospective trial was conducted to investigate first experiences with the use of targeted therapy and immunotherapy at the Centre and compare the results with the literature data. A total of 23 patients received BRAF targeted therapy for the treatment of metastatic cutaneous melanoma in the first line of treatment. Nine patients received vemurafenib, fourteen patients received a combination of BRAF/MEK inhibitor. Nine patients were treated with pembrolizumab immunotherapy. The trial was performed in a period from May 2017 until December 2020. Results: In patients receiving vemurafenib ORR was 44.4 %, median PFS was 5 months (95 % CI, 1 to 11) and the median OS was 9 months (95 % CI, 2 to 17). In the vemurafenib/cobimetinib group ORR was 71.4 %. Median PFS was 9 months and median OS was 12 months. ORR in patients receiving pembrolizumab was 22.9 %, median PFS was 3 months (95 % CI, 1 to 11) and the median OS was 4.5 months (95 % CI, 2 to 12). Results in all three groups were inferior compared to the results from the literature except for ORR in patients receiving vemurafenib and vemurafenib/cobimetinib. Adverse events were tolerable and manageable and were similar to those described in the literature. Conclusion: Based on the experience with the targeted and immunotherapy in the Centre, which was presented in this study, it was concluded that in conditions when there is limited access to drugs, the greatest benefit have the patients who meet the inclusion criteria in clinical trials.

A malignant peripheral nerve sheath tumour (MPNST) is a highly aggressive sarcoma. This disease develops in a number of people with neurofibromatosis type 1 (NF1), which is a common genetic disease. The paper presents a patient with typical manifestations of a malignant tumour of the peripheral nerve sheath, in the form of a large tumour of primary localisation in the distal part of the left thigh and left popliteal fossa and with significant dissemination into the lung parenchyma, which was accompanied by respiratory risk. The first operation of the tumour was done four years earlier, after which the patient did not come for regular check-ups. Nine cycles of chemotherapy were performed by Doxorubicin / Ifosfamide / Mesna protocol with clinical improvement and stabilisation, but without a significant impact on the dynamics of the disease and the overall survival was 14 months. It is of utmost importance to early recognise clinical presentation of the malignant form of this tumour and active supervision of a patient with a benign form by experts. In this way, it is possible to apply the optimal treatment modality in a timely manner.

Background Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. Results Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. Conclusions There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities.

Malignant salivary gland tumors form 11% of all head and neck tumors. Salivary duct carcinoma (SDC) of the parotid gland is an uncommon and highly aggressive tumor accounting for 2% of all salivary gland malignancies. The fourth edition of the WHO Classification of Head and Neck Tumors reported global annual incidence of 0.4–2.6/100,000 people. Standard treatment for SDC is wide surgical resection along with lymph node dissection followed by adjuvant radiation therapy. The role of adjuvant chemotherapy is not known. Here, we present a case of an SDC of the parotid gland in a 55-year-old female. She presented with a painless swelling behind her right ear. Surgery was performed, and total right parotidectomy was done along with selective neck dissection (levels II, III, VA). The pathology report concluded that it was a G3 (poorly differentiated) SDC (micropapillary variant) with lymphovascular and perineural invasion. The clinical stage of the disease was T4aN2bM0. Adjuvant therapy consisted of concurrent radiation (TD 66 Gy) and chemotherapy with weekly paclitaxel (45 mg/m2), carboplatin (AUC 1.5), and trastuzumab (2 mg/kg; THC) for 6 weeks followed by 4 cycles of THC every 3 weeks. Adjuvant trastuzumab was continued for a total of 1 year. She is still without the evidence of the disease 7 years later. The consensus regarding the use of adjuvant chemotherapy does not exist. Based on all the data that have been presented before, the conclusion is that we need new treatment modalities to improve the outome of this aggressive disease.

Introduction: Mixed adenoneuroendocrine carcinoma (MANEC) is a tumor of the gastrointestinal tract that contains both exocrine and endocrine components, with each component representing a minimum of 30% of the total tumor mass.

Background: Monoclonal antibodies (mAbs) represent the most numerous and significant group of biotherapeutics. While mAbs have undoubtedly improved treatment for many chronic diseases, including inflammatory diseases, they are typically expensive for health care systems and patients. Consequently, access to mAbs has been a problem for many patients especially among Central and Eastern European (CEE) countries. However, biosimilars can potentially help with costs, although there are concerns with their effectiveness and safety. This includes biosimilars for long-acting insulin analogues. Aim: Assess the availability and use of biological medicines, including biosimilars within Bosnia and Herzegovina (B&H). Methods: Assess the availability of mAbs via the current lists of approved and accessed mAbs versus those licenced in Europe and the United States and their utilisation, as well as specifically insulin glargine and its biosimilars, within B&H. Results: The availability of the mAbs in B&H appears satisfactory, which is encouraging. However, current usage is limited to a few mAbs which is a concern for subsequent patient care especially with limited use of biosimilars to address issues of affordability. We also see limited use of biosimilar insulin glargine. Conclusion The limited use of mAbs including biosimilars needs to be addressed in B&H to improve the future care of patients within finite resources. We will monitor these developments.

Background / Aim. FOLFOX (5fluorouracil, folinic acid, oxaliplatin)/CapOx (capecitabine, oxaliplatin) plus bevacizumab and FOLFIRI (5 fluorouracil, folinic acid, irinotecan) plus bevacizumab are a standard treatment options for a first line treatment of metastatic colorectal carcinoma (mCRC). The aim of this study was to compare overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the groups of patients with mCRC who were treated in the first line with FOLFIRI/bev versus FOLFOX/bev. At the same time, it was compared the safety profile in observed groups of patients and investigated optimal treatment duration and characteristics of patients who had the best treatment outcomes. Methods. In a retrospective-prospective study, patients with mCRC were treated with a chemotherapy protocols for the first line in combination with bevacizumab (FOLFOX/bev, respectively, FOLFIRI/bev). Treatment efficacy was evaluated on the basis of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS), and the safety of treatment was evaluated by monitoring adverse drug reactions. Results. ORR was 70% in the FOLFIRI/bev group and 50% in the FOLFOX/bev group. Median PFS for FOLFIRI/bev (n = 30) and for FOLFOX/bev (n = 30) was 15.6 months and 12.1 months respectively (HR, 0.85; 95% confidence interval (CI) 0.47-1.53; P = 0.5591). Median OS for FOLFIRI/bev and for FOLFOX/bev was 24.7 months and 19.9 months respectively (HR, 0.67; 95% confidence interval (CI) 0.37-1.23; P = 0.1552). In both patient groups, the patients who received more than 9 cycles of induction therapy had better treatment response in comparison with patients who received less than 9 cycles of therapy. In FOLFOX/bev group PFS was 16.9 versus 9.7 months and OS was 22.1 versus 17.6 months respectively. In FOLFIRI/bev group PFS was 9 months for patients who received less than 9 cycles of therapy versus 18.8 months for patients who received more than 9 cycles, OS was 18.0 versus 27.7 respectively. The adverse drug reactions grade 3 and 4 were 7% in the FOLFIRI/bev group versus 27% in the FOLFOX/bev group. Conclusion. Patients who received FOLFIRI/bev had better ORR (70 % versus 50 %), PFS (15.6 versus 12.1 months) and OS (24.7 versus 19.9 months). In both patient groups, better treatment response had the patients who received induction therapy for 4-6 months (more than 9 cycles of therapy).