An international comparative analysis and roadmap to sustainable biosimilar markets.

Background: Although biosimilar uptake has increased (at a variable pace) in many countries, there have been recent concerns about the long-term sustainability of biosimilar markets. The aim of this manuscript is to assess the sustainability of policies across the biosimilar life cycle in selected countries with a view to propose recommendations for supporting biosimilar sustainability. Methods: The study conducted a comparative analysis across 17 countries from North America, South America, Asia-Pacific, Europe and the Gulf Cooperation Council. Biosimilar policies were identified and their sustainability was assessed based on country-specific reviews of the scientific and grey literature, validation by industry experts and 23 international and local non-industry experts, and two advisory board meetings with these non-industry experts. Results: Given that European countries tend to have more experience with biosimilars and more developed policy frameworks, they generally have higher sustainability scores than the other selected countries. Existing approaches to biosimilar manufacturing and R&D, policies guaranteeing safe and high-quality biosimilars, exemption from the requirement to apply health technology assessment to biosimilars, and initiatives counteracting biosimilar misconceptions are considered sustainable. However, biosimilar contracting approaches, biosimilar education and understanding can be ameliorated in all selected countries. Also, similar policies are sometimes perceived to be sustainable in some markets, but not in others. More generally, the sustainability of the biosimilar landscape depends on the nature of the healthcare system and existing pharmaceutical market access policies, the experience with biosimilar use and policies. This suggests that a general biosimilar policy toolkit that ensures sustainability does not exist, but varies from country to country. Conclusion: This study proposes a set of elements that should underpin sustainable biosimilar policy development over time in a country. At first, biosimilar policies should guarantee the safety and quality of biosimilars, healthy levels of supply and a level of cost savings. As a country gains experience with biosimilars, policies need to optimise uptake and combat any misconceptions about biosimilars. Finally, a country should implement biosimilar policies that foster competition, expand treatment options and ensure a sustainable market environment.

Magnetic resonance imaging system for intraoperative margin assessment for DCIS and invasive breast cancer using the ClearSight™ system in breast-conserving surgery-Results from a postmarketing study.

BACKGROUND AND OBJECTIVES: Breast-conserving surgery (BCS) is followed by reoperations in approximately 25%. Reoperations lead to an increased risk of infection and wound healing problems as well as a worse cosmetic outcome. Several technical approaches for an intraoperative margin assessment to decrease the reoperation rate are under evaluation, some of them are still experimental. METHODS: A prospective single-arm post-marketing study with 60 patients undergoing BCS for ductal carcinoma in situ (DCIS) and invasive breast cancer was conducted. The specimen was intraoperatively examined by the ClearSight™ system, a mobile magnetic resonance imaging system that is based on a diffusion-weighted imaging protocol. However, the results were blinded to the surgeon. RESULTS: The ClearSight™ system was performed for both ductal and lobular breast cancer and DCIS, with a sensitivity of 0.80 (95% confidence interval [CI]: 0.44-0.96) and a specificity of 0.84 (95% CI 0.72-0.92), with an overall diagnostic accuracy of 80%. CONCLUSION: Had the ClearSight™ been known to the surgeon intraoperatively, the reoperation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% reoperations. A trial designed to examine the impact on reoperation rates is currently ongoing.

Update Breast Cancer 2021 Part 3 - Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel.

The continuous availability of findings from new studies repeatedly results in updated treatment recommendations and guidelines. In the case of breast carcinoma in particular, several studies have been published in the last few years that have transformed how early and advanced breast carcinoma is being treated. However, this by no means means implies that there is agreement among all experts on specific issues. It is precisely the diversity of interpretation of guidelines and study findings that reflects the constantly changing available data and its complexity, as well as the availability of new drugs. In recent years, new substances such as pertuzumab, T-DM1, neratinib and capecitabine have become available to treat patients with early stages of breast carcinoma. Furthermore, the first results on the use of CDK4/6 inhibitors for adjuvant treatment have now been published. Last but not least, the use of multigene tests to avoid the necessity of chemotherapy in certain patients is still under discussion. This review summarises the state of the data and publishes the results of the survey completed by experts at the 2021 St. Gallen Breast Cancer Conference on early-stage breast cancer.

ABC3 Consensus: Assessment by a German Group of Experts.

The Advanced Breast Cancer Third International Consensus Conference on the diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment of metastatic breast cancer (stage IV), as it was 4 years ago at the first consensus meeting (ABC1). A matter of particular interest was the patients' perspective. Thus, patient-relevant issues were addressed by the consensus discussions, such as those on treatment goals, quality of life, care of long-term survivors ('survivorship issues'), and coping with disease-related symptoms and the side effects of treatment. Further important issues on the agenda were the use of standardized instruments for the assessment of individual treatment success ('patient-reported outcome measures') and the evaluation of the benefit of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally advanced breast cancer had already been discussed 2 years earlier at the ABC2 Consensus and were not dealt with in the framework of this year's ABC3 Consensus. With regard to country-specific peculiarities, which unavoidably found their way into the ABC Consensus, a working group of German breast cancer experts commented on the voting results of the ABC panelists. As for the past consensus, the group specially considered the German guidelines for the diagnosis and treatment of breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for everyday therapy in Germany.

Intraoperative assessment of margins in breast conservative surgery--still in use?

A positive margin in breast conserving surgery is associated with an increased risk of local recurrence. Failure to achieve clear margins results in re-excision procedures. Methods for intraoperative assessment of margins have been developed, such as frozen section analysis, touch preparation cytology, near-infrared fluorescence optical imaging, x-ray diffraction technology, high-frequency ultrasound, micro-CT, and radiofrequency spectroscopy. In this article, options that might become the method of choice in the future are discussed.

MarginProbe: intraoperative margin assessment during breast conserving surgery by using radiofrequency spectroscopy.

In breast conserving surgery, the tumor should be removed with a clean margin, a rim of healthy tissue surrounding. Failure to achieve clean margins in the initial surgery results in a re-excision procedure. Re-excision rates are reported as being 11-46% for invasive carcinoma and ductal carcinoma in situ (DCIS). Re-excisions can have negative consequences such as increased postoperative infections, negative impact on cosmesis, patient anxiety and increased medical costs. Therefore, the surgical margin of invasive and intraductal (DCIS) breast tissue is a subject of intense discussion. Different options for intraoperative assessment are available, but all in all, they are unsatisfying. Frozen section margin examination is possible but is time consuming and restricted to the assessment of invasive carcinoma. In the case of DCIS, there is no procedure for intraoperative margin assessment. Thus, a solution for efficient intraoperative surgical margin assessment is needed. For this purpose, an innovative, real-time, intraoperative margin-assessment device (MarginProbe, Dune Medical Devices, Caesarea, Israel) was designed, and recent published clinical data reported a reduction of re-excisions by more than 50%.

Intraoperative assessment of surgical margins during breast conserving surgery of ductal carcinoma in situ by use of radiofrequency spectroscopy.

Assessment of margins when excising ductal carcinoma in situ (DCIS) of the breast is difficult. Frozen section is unreliable and specimen intraoperative radiography only provides information regarding the extent of the visualized lesion or the microcalcifications. A multi-center, single arm study was conducted to evaluate the benefit of a novel device (MarginProbe) in intraoperative margin assessment during breast conserving surgery (BCS) of DCIS, and the associated reduction of re-excisions. We present results for 22 patients, from those enrolled in our institution. The device was used as an adjunctive tool to current practice. Based on permanent histology reporting, the rate of successful procedures was 86%. The improvement in intraoperative assessment with device use was associated with a reduction in re-excision rates, from 38.8 to 18%.

The utility of an in vitro angiogenesis score for prognosis assessment in patients with cervical cancer.

BACKGROUND/AIM: Angiogenesis plays a key role in tumour growth and metastasis. Expression of angiogenic factors has been suggested as a marker for tumour malignity, and may help to assess a patient's individual prognosis. The present study examines the relationship between angiogenic factor expression, an angiogenesis-based histoscore and clinical tumour criteria. PATIENTS AND METHODS: A total of 81 patients with cervical cancer who underwent follow-up examinations between October 2002, and June 2005, were enrolled, and serum samples were examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and VEGF-Receptor1 by means of an ELISA. Based on an endothelial-cell proliferation assay, an angiogenesis score was calculated. RESULTS: Higher endostatin and VEGF expressions indicated advanced disease, and VEGF allowed for a reliable distinction between patients with non-invasive and these with recurrent disease. There were some plausible correlations between the angiogenesis score and clinical criteria and individual angiogenic factors, but the score's discriminating power appears to be limited. CONCLUSION: The utility of angiogenesis factor testing notwithstanding, the value of an angiogenesis score for the identification of patients with a worse prognosis, and thus a resulting benefit from more aggressive treatment, is arguable.