Off-label use in germany - a current appraisal of gynaecologic university departments

<p>Abstract</p> <p>Objective</p> <p>The off-label use, referring to the applicability of pharmaceutical drugs beyond the submitted and from the Federal Institute for Drugs and Medical Devices (BfArM, Bundesamt für Arzneimittel und Medizinprodukte) certified and approved administration, is the subject of controversial discussions. the application can be considered in case of severe illness - if no therapeutic alternatives are available - or it exists as a founded perspective for achieving therapeutic success.</p> <p>Methods</p> <p>A latitudinal study for evaluating the application of off-label use supplements was performed at 43 German university and academic teaching hospitals. Five doctors at each hospital applied off-label pharmaceutical drugs and were called upon to share their personal experience to the application of those medications.</p> <p>Results</p> <p>75 (35%) questionnaires were returned out of 22 (51%) medical centres with 215 contacted physicians. Off-label use was common for 65 (91%) of the physicians. Only 9% of them obviate the application of off-label drugs. About a half of the medication is related to application in obstetrics (54%) and in most cases on an every day basis. Uterotonics were the most commonly used off-label medications (34%). The main part of information about off-label use is obtained from personal information of colleagues (66%) and personal experience (58%). 34% of physicians think that off label use is risky. Interestingly, the view about off label use of medication varies considerably among physicians from various hospitals.</p> <p>Conclusions</p> <p>The application of off-label pharmaceutical drugs in Germany seems to be a well established practice. More than 90% of participators of our trial use at least one medication outside the administration. This includes particularly prostaglandins, anti-hyper-tonic therapeutics and chemotherapeutics.</p

Fibrin Sealants and Axillary Lymphatic Morbidity. A Systematic Review and Meta-Analysis of 23 Clinical Randomized Trials

Background: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenec- tomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. Methods: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. Results: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin’s disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p &lt; 0.0001, p &lt; 0.005, p = 0.008). Conclusion: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found

Update breast cancer 2021 part 5 – advanced breast cancer

Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials

Update breast cancer 2021 part 4 – prevention and early stages

This past year has seen new and effective options for further improving treatment outcome in many patients with early-stage breast cancer. Patients with hormone receptor-positive disease benefited significantly from the addition of the CDK4/6 inhibitor abemaciclib to endocrine adjuvant therapy. In triple-negative disease, data were presented for two treatment regimens. Patients with advanced disease (stage 2 and 3) benefit from neoadjuvant treatment with the immune checkpoint inhibitor pembrolizumab in combination with standard chemotherapy, regardless of PD-L1 expression. When neoadjuvant therapy has failed to achieve the desired remission in BRCA1 and BRCA2 mutations, the administration of the PARP inhibitor olaparib has demonstrated an impressive response. Other data address translational issues in HER2-positive breast cancer and neoadjuvant therapy approaches with the oral SERD giredestrant and the PARP inhibitor talazoparib. This review presents and analyses the findings of this yearʼ s most important study outcomes

Update breast cancer 2022 part 5: early stage breast cancer

The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies

Update breast cancer 2022 part 4 – advanced-stage breast cancer

For the treatment of patients with advanced HER2-negative hormone receptor-positive breast cancer, several substances have been introduced into practice in recent years. In addition, other drugs are under development. A number of studies have been published over the past year which have shown either an advantage for progression-free survival or for overall survival. This review summarizes the latest results, which have been published at current congresses or in specialist journals, and classifies them in the clinical treatment context. In particular, the importance of therapy with CDK4/6 inhibitors – trastuzumab deruxtecan, sacituzumab govitecan and capivasertib – is discussed. For trastuzumab deruxtecan, an overall survival benefit in HER2-negative breast cancer with low HER2 expression (HER2-low expression) was reported in the Destiny-Breast-04 study. Similarly, there was an overall survival benefit in the FAKTION study with capivasertib. The lack of overall survival benefit for palbociclib in the first line of therapy raises the question of clinical classification

Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer

The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies

Update Breast Cancer 2022 part 3 – Early-stage breast cancer

This review summarizes recent developments in the prevention and treatment of patients with early-stage breast cancer. The individual disease risk for different molecular subtypes was investigated in a large epidemiological study. With regard to treatment, new data are available from long-term follow-up of the Aphinity study, as well as new data on neoadjuvant therapy with atezolizumab in HER2-positive patients. Biomarkers, such as residual cancer burden, were investigated in the context of pembrolizumab therapy. A Genomic Grade Index study in elderly patients is one of a group of studies investigating the use of modern multigene tests to identify patients with an excellent prognosis in whom chemotherapy may be avoided. These and other aspects of the latest developments in the diagnosis and treatment of breast cancer are described in this review

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. A Osorio1, R L Milne2, G Pita3, P Peterlongo4,5, T Heikkinen6, J Simard7, G Chenevix-Trench8, A B Spurdle8, J Beesley8, X Chen8, S Healey8, KConFab9, S L Neuhausen10, Y C Ding10, F J Couch11,12, X Wang11, N Lindor13, S Manoukian4, M Barile14, A Viel15, L Tizzoni5,16, C I Szabo17, L Foretova18, M Zikan19, K Claes20, M H Greene21, P Mai21, G Rennert22, F Lejbkowicz22, O Barnett-Griness22, I L Andrulis23,24, H Ozcelik24, N Weerasooriya23, OCGN23, A-M Gerdes25, M Thomassen25, D G Cruger26, M A Caligo27, E Friedman28,29, B Kaufman28,29, Y Laitman28, S Cohen28, T Kontorovich28, R Gershoni-Baruch30, E Dagan31,32, H Jernström33, M S Askmalm34, B Arver35, B Malmer36, SWE-BRCA37, S M Domchek38, K L Nathanson38, J Brunet39, T Ramón y Cajal40, D Yannoukakos41, U Hamann42, HEBON37, F B L Hogervorst43, S Verhoef43, EB Gómez García44,45, J T Wijnen46,47, A van den Ouweland48, EMBRACE37, D F Easton49, S Peock49, M Cook49, C T Oliver49, D Frost49, C Luccarini50, D G Evans51, F Lalloo51, R Eeles52, G Pichert53, J Cook54, S Hodgson55, P J Morrison56, F Douglas57, A K Godwin58, GEMO59,60,61, O M Sinilnikova59,60, L Barjhoux59,60, D Stoppa-Lyonnet61, V Moncoutier61, S Giraud59, C Cassini62,63, L Olivier-Faivre62,63, F Révillion64, J-P Peyrat64, D Muller65, J-P Fricker65, H T Lynch66, E M John67, S Buys68, M Daly69, J L Hopper70, M B Terry71, A Miron72, Y Yassin72, D Goldgar73, Breast Cancer Family Registry37, C F Singer74, D Gschwantler-Kaulich74, G Pfeiler74, A-C Spiess74, Thomas v O Hansen75, O T Johannsson76, T Kirchhoff77, K Offit77, K Kosarin77, M Piedmonte78, G C Rodriguez79, K Wakeley80, J F Boggess81, J Basil82, P E Schwartz83, S V Blank84, A E Toland85, M Montagna86, C Casella87, E N Imyanitov88, A Allavena89, R K Schmutzler90, B Versmold90, C Engel91, A Meindl92, N Ditsch93, N Arnold94, D Niederacher95, H Deißler96, B Fiebig97, R Varon-Mateeva98, D Schaefer99, U G Froster100, T Caldes101, M de la Hoya101, L McGuffog49, A C Antoniou49, H Nevanlinna6, P Radice4,5 and J Benítez1,3 on behalf of CIMB