Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

A case report of the sustained and rapid response of bevacizumab in a TP53-positive breast cancer and liver metastatic patient through personalized medicine.

HER2-positive metastatic breast cancer is much less frequent than other subgroups of breast cancer. Treatment options for this cancer are mostly limited to systemic chemotherapy, which leads to moderate improvements. Targeted therapy against malignant breast cancer requires the identification of reliable biomarkers for personalized medicine to obtain the maximum benefit of this therapy. Any mutations in the TP53 signaling pathway can be considered as a significant causative factor of breast cancer, for which the identification of target genes plays an important role in selecting the appropriate treatment. The use of personalized gene expression profiling could be valuable to find the direct target of the treatment in this case. The present study assessed the genetic profile of an HER2-positive metastatic breast cancer patient (with a liver metastasis) and figured out a complete and sustained response to bevacizumab. According to the results of next-generation sequencing (NGS) analysis, the patient's genetic profile showed an increased expression of p4EBP1 and PTEN and the activation of the mTOR signaling pathway with a mutation in the TP53 gene. Based on the common treatment of similar profiling, we administrated bevacizumab/Taxol/Gemzar chemotherapy up to six courses. Accordingly, as the response to treatment was revealed by reducing the volume of the liver metastasis from 4 to 1.4 cm, metastasectomy was performed as a complementary treatment. Hence, personalized gene expression profiling not only is useful for targeted therapy but also could be recommended to avoid prescription of non-responsive drugs.

Effectiveness of Integrating Simulation with Art-Based Teaching on Attitudes of Oncology Fellows for Learning Communication Skills: a Pilot Study.

Integration of simulated practice with art-based teaching strategy can be effective for learning communication skills. This pilot study outlines the effect of integrating simulation with art-based teaching strategies on the attitudes of oncology fellows toward learning communication skills. The study was conducted in Iran using a quasi-experimental method. The participants were the oncology fellows of Tehran University of Medical Sciences (n = 19). The intervention was 1-day workshop, followed by integrating simulation with different types of art-based teaching methods. The Communication Skills Attitude Scale (CSAS) was used to assess the effectiveness of the developed model. Our finding indicated that the mean values of oncology fellows' attitude scores in all domains of CSAS including importance in medical context (53.26 ± 2.13vs 41.00 ± 5.01, p = 0.001), excuse (25.84 ± 3.01vs14.36 ± 2.62, p = 0.001), learning (23.26 ± 1.40vs8.89 ± 2.25, p = 0.001), overconfidence (13.10 ± 1.44 vs 5.57 ± 1.38, p = 0.001), and overall (115.47 (5.51) vs 69.84(6.51) p = 0.001) increased significantly after the intervention as compared with before it. Findings support the hypothesis that using integrated training methods may help oncology fellows to appreciate the importance of communication skills learning. The implications of this hypothesis are that the inclusion of integrating simulation with art-based teaching strategies in the medical curriculum can improve the attitude of oncology fellows during their education.

Effectiveness of Integrating Simulation with Art-Based Teaching Strategies on Oncology Fellows' Performance Regarding Breaking Bad News.

The task of breaking bad news (BBN) may be improved by incorporating simulation with art-based teaching methods. The aim of the present study was to assess the effect of an integrating simulation with art-based teaching strategies, on fellows' performance regarding BBN, in Iran. The study was carried out using quasi-experimental methods, interrupted time series. The participants were selected from medical oncology fellows at two teaching hospitals of Tehran University of Medical Sciences (TUMS), Iran. Participants were trained through workshop, followed by engaging participants with different types of art-based teaching methods. In order to assess the effectiveness of the integrating model, fellows' performance was rated by two independent raters (standardized patients (SPs) and faculty members) using the BBN assessment checklist. This assessment tool measured seven different domains of BBN skill. Segmented regression was used to analyze the results of study. Performance of all oncology fellows (n = 19) was assessed for 228 time points during the study, by rating three time points before and three time points after the intervention by two raters. Based on SP ratings, fellows' performance scores in post-training showed significant level changes in three domains of BBN checklist (B = 1.126, F = 3.221, G = 2.241; p < 0.05). Similarly, the significant level change in fellows' score rated by faculty members in post-training was B = 1.091, F = 3.273, G = 1.724; p < 0.05. There was no significant change in trend of fellows' performance after the intervention. Our results showed that using an integrating simulation with art-based teaching strategies may help oncology fellows to improve their communication skills in different facets of BBN performance. Iranian Registry of Clinical Trials ID: IRCT2016011626039N1.

Construction and functional characterization of a fully human anti-CD19 chimeric antigen receptor (huCAR)-expressing primary human T cells.

Although remarkable results have been attained by adoptively transferring T cells expressing fully murine and/or humanized anti-CD19 chimeric antigen receptors (CARs) to treat B cell malignancies, evidence of human anti-mouse immune responses against CARs provides a rationale for the development of less immunogenic CARs. By developing a fully human CAR (huCAR), these human anti-mouse immune responses are likely eliminated. This, perhaps, not only increases the persistence of anti-CD19 CAR T cells-thereby reducing the risk of tumor relapse-but also facilitates administration of multiple, temporally separated doses of CAR T cells to the same recipient. To these ends, we have designed and constructed a second-generation fully human anti-CD19 CAR (or huCAR19) containing a fully human single-chain variable fragment (ScFv) fused with a CD8a hinge, a 4-1BB transmembrane domain and intracellular T cell signaling domains of 4-1BB and CD3z. T cells expressing this CAR specifically recognized and lysed CD19+ target cells produced cytokines and proliferated in vitro. Moreover, cell volume data revealed that our huCAR construct cannot induce antigen-independent tonic signaling in the absence of cognate antigen. Considering our results, our anti-CD19 huCAR may overcome issues of transgene immunogenicity that plague trials utilizing CARs containing mouse-derived ScFvs. These results suggest that this huCAR19 be safely and effectively applied for adaptive T cell immunotherapy in clinical practice.

Exploring experience of Iranian medical sciences educators about Best Evidence Medical Education: A content analysis.

BACKGROUND AND OBJECTIVE: Applying the Best Evidence Medical Education (BEME) in real educational arena is a necessity in medical education. As to the literature, there are enough evidence; however, their application by educators and policymakers has been still failed. Therefore, this study conducted to explore the experience of educators about applying BEME in Iranian context. MATERIALS AND METHODS: Qualitative approach using content analysis method was utilized for exploring 25 participants involved with medical education in different levels, introduced the study using purposeful sampling. Data were collected through a semi-structured interview by which they answered to researcher's questions in around 45 min about how they apply evidence in their educational setting. To make more clarification, probing questions were used. Interviews were recorded and transcribed and then analyzed by coding paradigm immediately. RESULTS: Three categories were emerged as: applying different levels of evidence, substitution of evidence-based medicine for BEME, and variation of understanding BEME. The first category includes subcategories of using personal experience, textbooks, and filtered papers. The second contains lack of knowledge about BEME elements, time and motivation as well as no priority for applying available medical education evidence; and third, using different terminology and having some problems in applying process, based on individual understanding and using papers with or without modification. DISCUSSION: For effective evidence application, it is necessary to operationalize BEME terminology and overcome any ambiguity surrounded it. It is also important to suggest educators to apply the appraised evidence as well as teach them how they search and appraise evidence independently. Certainly, in the first steps, supervision and providing a proper context for BEME applications are crucial.

Psychometric properties of the communication skills attitude scale (CSAS) measure in a sample of Iranian medical students.

INTRODUCTION: Communication skill (CS) has been regarded as one of the fundamental competencies for medical and other health care professionals. Student's attitude toward learning CS is a key factor in designing educational interventions. The original CSAS, as positive and negative subscales, was developed in the UK; however, there is no scale to measure these attitudes in Iran. The aim of this study was to assess the psychometric characteristic of the Communication Skills Attitude Scale (CSAS), in an Iranian context and to understand if it is a valid tool to assess attitude toward learning communication skills among health care professionals. METHODS: Psychometric characteristics of the CSAS were assessed by using a cross-sectional design. In the current study, 410 medical students were selected using stratified sampling framework. The face validity of the scale was estimated through students and experts' opinion. Content validity of CSAS was assessed qualitatively and quantitatively. Reliability was examined through two methods including Chronbach's alpha coefficient and Intraclass Correlation of Coefficient (ICC). Construct validity of CSAS was assessed using confirmatory factor analysis (CFA) and explanatory factor analysis (PCA) followed by varimax rotation. Convergent and discriminant validity of the scale was measured through Spearman correlation. Statistical analysis was performed using SPSS 19 and EQS, 6.1. RESULTS: The internal consistency and reproducibility of the total CSAS score were 0.84 (Cronbach's alpha) and 0.81, which demonstrates an acceptable reliability of the questionnaire. The item-level content validity index (I-CVI) and the scale-level content validity index (S-CVI/Ave) demonstrated appropriate results: 0.97 and 0.94, respectively. An exploratory factor analysis (EFA) on the 25 items of the CSAS revealed 4-factor structure that all together explained %55 of the variance. Results of the confirmatory factor analysis indicated an acceptable goodness-of-fit between the model and the observed data. [χ2/df = 2.36, Comparative Fit Index (CFI) = 0.95, the GFI=0.96, Root Mean Square Error of Approximation (RMSEA) = 0.05]. CONCLUSION: The Persian version of CSAS is a multidimensional, valid and reliable tool for assessing attitudes towards communication skill among medical students.