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.

Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer.

BACKGROUND: CRC is the second and third most common cancer in women and men, respectively. The national comprehensive cancer network guidelines recommend oxaliplatin-based chemotherapy as a preferred regimen for patients with advanced or metastatic colon cancer. Oxaliplatin is also used in the off-label treatment of gastric cancer. FDA uses post-marketing study commitments to gather additional information about a product's safety, efficacy, or optimal use. It is necessary to perform safety monitoring after marketing authorization is received; such monitoring can be done by means of characterizing the safety of drugs in patients being treated in real-world clinical practice settings. OBJECTIVES: This Phase IV study aimed to evaluate the safety profile of a brand-name formulation of the generic drug oxaliplatin (AlvoxalⓇ, NanoAlvand, Tehran, Iran) in Iranian patients diagnosed with either colorectal or other, different types of cancer. METHODS: Patients with colorectal cancer, gastric cancer, or other malignancies receiving oxaliplatin as a part of their treatment were included in this open-label, multicenter, observational Phase IV study. This study aimed to assess the safety profile of oxaliplatin in patients diagnosed with different cancers. FINDINGS: A total of 483 patients from 16 cities in Iran were enrolled. The most common malignancy was colorectal cancer (55.49%), followed by gastric cancer (28.16%). Based on the results, 405 patients experienced at least 1 adverse event. Most of these adverse events were grade 1 or 2, and the most commonly reported adverse event was anemia (60.66%). During the study, 26 serious adverse events occurred in 15 (3.11%) patients, which were perhaps related to oxaliplatin. There were no remarkable differences in the incidences of adverse events in the system organ classes of blood and lymphatic system disorders, gastrointestinal disorders, or nervous system disorders among patients with different malignancies (ie, colorectal cancer, gastric cancer, and other malignancies) or between genders. The results of this open-label, multicenter, observational, postmarketing surveillance study demonstrated no unexpected safety findings from the use of this oxaliplatin product (AlvoxalⓇ) in Iranian patients diagnosed with different types of cancer. CONCLUSIONS: This Phase IV study provides data on the safety profile of a number of chemotherapy regimens containing an oxaliplatin product given to Iranian patients diagnosed with different types of cancer.

A Post-Marketing Surveillance Study to Evaluate the Safety Profile of AlvotereⓇ (Docetaxel) in Iranian Patients Diagnosed with Different Types of Cancers Receiving Chemotherapy.

BACKGROUND: Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non-small cell lung cancer, and prostate cancer. OBJECTIVE: This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel. METHODS: Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets. FINDINGS: A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants' mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher (P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens. CONCLUSIONS: The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

Efficacy of topical Lawsonia inermis L. (Henna) hydrogel in fluorouracil-induced hand-foot syndrome: a pilot randomized double-blind placebo-controlled clinical trial.

PURPOSE: Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of fluoropyrimidine drugs like capecitabine and 5-flourouracil (5-FU) in breast and gastrointestinal cancers. It has been shown that conventional application of Lawsonia inermis L. (Henna) is effective in ameliorating of the skin lesions. To increase the patient compliance, in this study we formulated a standardized topical hydrogel (H.gel) containing the hydroalcoholic extract (10%) of Henna and evaluated its clinical efficacy for the management of fluorouracil associated HFS. MATERIAL AND METHODS: The topical dosage form was standardized based on its Lawsone content. Eighteen patients suffering from HFS were randomized to receive H.gel and the placebo four times a day for 2 weeks. At the baseline and at the end of the trial, HFS grades were determined. RESULTS AND CONCLUSIONS: Allergic reactions following administration of H.gel were observed in one patient, while no serious adverse events occurred in the others. No statistically significant differences between two arms were observed at the baseline (p-value = 0.133), after treatment (p-value = 0.590) and grade differences (p-value = 0.193). The applied hydrogel showed less efficacy compared to the traditional method of using Henna, meaning that Lawsone may not be a good indicator for standardizing the topical dosage form.

Management of colon and rectal cancers during COVID-19 pandemic: A clinical guideline (TUMS-CRC-CoV19 Guideline).

Background: In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was performed to design a guideline to manage patients with colorectal cancers during the COVID-19pandemic. Methods: To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline. Results: This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B. Conclusion: This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.

Successful desensitization of a patient with cetuximab hypersensitivity: A case report.

BACKGROUND: Severe hypersensitivity reaction is a dangerous adverse drug reaction in patients receiving cetuximab. It requires drug discontinuation and medical management. CASE DESCRIPTION: A 48-year-old man, previously diagnosed with metastatic colorectal cancer, was admitted for therapy continuation. During the first infusion of cetuximab, the patient experienced acute signs of hypersensitivity reactions. The treatment team decided to administer cetuximab employing the desensitization protocol. CONCLUSIONS: This study reports a severe hypersensitivity reaction to cetuximab in an adult patient with colorectal cancer. This patient was successfully managed with a new safe and rapid desensitization protocol.

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.

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.

Contextualization and validation of the interprofessional collaborator assessment rubric (ICAR) through simulation: Pilot investigation.

BACKGROUND: Simulation can be used for educating, evaluating and assessing psychometric properties of an instrument. The aim of this study was to contextualize and assess the validity and reliability of the Interprofessional Collaborative Assessment tool (ICAR) in an Iranian context using simulation. METHODS: In this descriptive study, contextualization of the ICAR was assessed through several steps. Firstly, validity assessment was approved through expert panels and Delphi rounds. Secondly, reliability assessment was done by arranging a simulation video and assessing reproducibility, test-retest (ICC), internal consistency (Cronbach's Alpha) and inter-rater reliability (Kappa).The participants included 26 experts, 27 students and 6 staff of the Standardized Simulation Office of Teheran University of Medical Sciences. RESULTS: Contextualization and validity of the ICAR were approved in an Iranian context. The reliability of the tool was computed to be 0.71 according to Cronbach´s Alpha. The test-retest was calculated to be 0.76. CONCLUSION: The Iranian ICAR can be a useful tool for evaluating interprofessional collaborative competencies. The development of the instrument through a simulation scenario has been a positive prospect for researchers.

Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment.

Comparative Study of the Effects of Duloxetine and Venlafaxine on Acute Symptomatic Taxane-induced Neuropathy in Breast Cancer Patients: A Randomized Clinical Trial.

Introduction: Chemotherapeutic agents have the potential to induce neurotoxicity, resulting in a range of symptoms, including mild paresthesia, neuropathic pain, pronounced ataxia, and significant impairment. Taxane-induced neuropathy (TIN) is a prevalent adverse effect and a significant constraint of Taxane-based chemotherapy protocols in treating breast cancer. In this current study, we aim to compare the effects of Venlafaxine and Duloxetine in taxane-induced Neuropathy as well as the quality of life, Depression, and Anxiety in Breast cancer Patients. Methods: The present study investigated breast cancer patients who experienced acute neuropathic pain after receiving paclitaxel treatment, a chemotherapeutic agent. The participants were allocated randomly into two groups, one receiving Venlafaxine and the other receiving Duloxetine. The participants underwent assessments for anxiety, depression, pain, neuropathy, quality of life, and neuropathic pain through the administration of questionnaires at the commencement of the study and after ten weeks following the intervention. Results: Both groups exhibited decreased neuropathic pain, with the venlafaxine group significantly reducing McGill's pain score. Although, the result is not suggestive of a difference between venlafaxine and duloxetine impact on any variables scores. Conclusion: Duloxetine and Venlafaxine effectively treat neuropathic symptoms such as paraesthesia, tingling, and itching. Venlafaxine is also beneficial for relieving pain associated with neuropathy.This trial was retrospectively registered on 1.1.2023 at irct.ir (trial registration ID: IRCT20220115053723N1). URL: https://www.irct.ir/trial/62540/pdf.

Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis.

Background & aim: The histologic and molecular changes from intestinal metaplasia (IM) to gastric cancer (GC) have not been fully characterized. The present study sought to identify potential alterations in signaling pathways in IM and GC to predict disease progression; these alterations can be considered therapeutic targets. Materials & methods: Seven gene expression profiles were selected from the GEO database. Discriminate differentially expressed genes (DEGs) were analyzed by EnrichR. The STRING database, Cytoscape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, NetworkAnalyst, MirWalk database, OncomiR, and bipartite miRNA‒mRNA correlation network was used for downstream analyses of selected module genes. Results: Analyses revealed that extracellular matrix-receptor interactions (ITGB1, COL1A1, COL1A2, COL4A1, FN1, COL6A3, and THBS2) in GC and PPAR signaling pathway interactions (FABP1, APOC3, APOA1, HMGCS2, and PPARA and PCK1) in IM may play key roles in both the carcinogenesis and progression of underlying GC from intestinal metaplasia. IM enrichment indicated that this is closely related to digestion and absorption. The TF-hub gene regulatory network revealed that AR, TCF4, SALL4, and ESR1 were more important for hub gene expression. It was revealed that the development and prediction of GC may be affected by hsa-miR-29. It was found that PTGR1, C1orf115, CRYL1, ALDOB, and SULT1B1 were downregulated in GC and upregulated in IM. Therefore, they might have tumor suppressor activity in GC progression. Conclusion: New potential biomarkers and pathways involved in GC and IM were identified that are important for the transformation of GC from IM to adenocarcinoma and can be therapeutic targets for GC.

Tamoxifen retinopathy.

Tamoxifen (TAM) is a selective estrogen receptor modulator that is used in the treatment of breast cancer. As there are estrogen receptors in the retina, retinal pigment epithelium, and choroid, these tissues may also be affected by TAM. We describe the reported effects of TAM on the retina and choroid. Medical databases were searched using relevant keywords and the results were extracted and pooled. The incidence of retinal/choroidal toxicity ranged from 0.9% to 12%. There was a wide range for the time of exposure before the development of TAM retinopathy (3 weeks to 13 years). While functional measurements may be appropriate for assessment of TAM retinopathy, they have not been effective for screening patients. There is no generally accepted screening modality, but serial funduscopy and optical coherence tomography imaging seem to be the most reasonable approach for detecting early TAM-induced retinal toxicity.

Pharmaceutical and clinical studies of celecoxib topical hydrogel for management of chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) can be categorized as a frequent dose-limiting side effect following administration of chemotherapeutic agents, which needs an effective medication to avoid dose reduction or discontinuation. Oral celecoxib has been proved to be the best pharmacological intervention to ameliorate the skin lesions. However, due to reported gastrointestinal and cardiovascular toxicity following its long-term administration, celecoxib topical application would be a safe alternative for skin disorders. In this work, first, we formulated and optimized a topical hydrogel of celecoxib (1%) and then we investigated its efficacy in the management of chemotherapy-induced HFS in cancer patients. Optimized hydrogel showed acceptable results for drug content, pH, rheology, and stability. Analyzing in vitro drug release study by various mathematical models, the optimized hydrogel showed a zero-order release pattern with 93.27 ± 1.56% cumulative celecoxib release within 8 h. Ex vivo permeation studies across Wistar rat skin indicated suitable skin retention of celecoxib for topical delivery. Twenty-nine patients suffering from HFS were randomized to receive celecoxib and the placebo hydrogels 2 times a day for 3 weeks. At the baseline and at the end of the trial, HFS grades were determined. No serious adverse events occurred in patients who completely followed the instructions. No statistically significant differences between two arms were observed at the baseline (p value = 0.38). By contrast, Wilcoxon signed-rank test showed significant differences when secondary grades (p value = 0.05) and grade differences (p values < 0.001) were analyzed. Overall, the study proved that celecoxib hydrogel could be a promising intervention to manage HFS side effect.

The Evaluation of Hematological Parameters and Their Correlation with Disease Prognosis in COVID-19 Disease in Iran.

Background: Since 2019, Coronavirus has been a highly contagious disease. The COVID-19 outbreak was declared a pandemic by the World Health Organization in March 2020. Variable laboratory findings are reported in COVID-19 patients, among which elevated levels of D-dimer, lactate dehydrogenase, as well as lymphopenia, have been reported to be associated with increased severity of disease symptoms requiring ventilator support, intensive care unit admission, and mortality. Materials and Methods: In the current study, inclusion criteria were: patient age above 18 years and hospitalization in the Imam Khomeini hospital with COVID-19 disease confirmed with nasopharyngeal swab polymerase chain reaction tests. Levels of white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, D-dimer, C-reactive protein, LDH, and ferritin were measured and their correlation with the final patients' outcome was evaluated. Results: A total of 208 patients were included in the present study. Higher neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, and D-dimer were significantly related to O2 dependency. Neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte and LDH were significantly related to higher rates of mortality. Higher Hb and lymphocyte count were significantly related to higher rates of survival. Conclusion: Hematological parameters including neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, D-dimer, Hb, and lymphocyte count were significantly related to the prognosis of patients with COVID-19 disease. This could help decide which COVID-19 patients have priority for hospitalization and intensive medical care, particularly when the pandemic disease causes limitations in healthcare service.

Hyepereosiniphilic syndrome and COVID-19: 2 case reports.

BACKGROUND: Nearly half of the patients with hypereosinophilic syndrome (HES) have cardiovascular involvement, a major cause of mortality. COVID-19 infection can lead to cardiac involvement, negatively impacting the clinical course and prognosis. We reported two patients with HES complicated by COVID-19, with cardiac involvement and valve replacement. CASE PRESENTATION: Our first patient was a 27-year-old woman admitted due to dyspnea and signs of heart failure. She had severe mitral stenosis and mitral regurgitation on the echocardiogram. Corticosteroid therapy improved her symptoms initially, but she deteriorated following a positive COVID-19 test. A repeated echocardiogram showed right ventricular failure, severe mitral regurgitation, and torrential tricuspid regurgitation and, she underwent mitral and tricuspid valve replacement. Our second patient was a 43-year-old man with HES resulted in severe tricuspid stenosis, which was improved with corticosteroid treatment. He underwent tricuspid valve replacement due to severe valvular regurgitation. He was admitted again following tricuspid prosthetic mechanical valve thrombosis. Initial workups revealed lung involvement in favor of COVID-19 infection, and his PCR test was positive. CONCLUSION: COVID-19 infection can change the clinical course of HES. It may result in a heart failure exacerbation due to myocardial injury and an increased risk of thrombosis in prosthetic valves or native vessels due to hypercoagulability.

A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients.

BACKGROUND: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. METHODS: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. CONCLUSIONS: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.

Conflict of Interest: Are Iranian Breast Cancer Specialists Prone to it?

INTRODUCTION: Giving gifts is a common way to promote and encourage the use of products of trading companies and increase the patient referrals to diagnostic centers. The present study aimed to assess the practice of physicians of different (sub) specialties/educational levels engaged in breast cancer management in some conflict of interest (COI) situations in their relation with pharmaceutical companies and paraclinical centers. METHODS: A self-administered online questionnaire including questions on demographic and professional information as well as the attitude of physicians toward COI by answering the questions in three different practical scenarios was developed. Respondents were asked to answer each question by selecting one of the five options: strongly agree, agree, undecided/neutral, disagree, and strongly disagree in their own practices as well as the same questions asking the same subject for what they think of the other physicians. Descriptive statistical analysis was used to report qualitative and quantitative variables. RESULT: The response rate was 66.24%. In general, physicians considered their performance better than that of other physicians in the situations asked. More than 90% stated that they would participate in the sponsorship congress for introducing new drugs. One fifth of the physicians stated that they would accept the 30% financial proposition for the referral of every single patient to other clinics. More than half of the physicians stated that they had considered the risks resulted from the COI for referring patients to private radiobiological centers. CONCLUSION: This study indicated that physicians in the field of breast cancer were at the risk of COI. Even within the medical field, there is not sufficient trust in the proper functioning of doctors in dealing with COI situations.
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