Evaluation of biosimilar trastuzumab MYL-1401O in HER2-positive breast cancer.

OBJECTIVES: The trastuzumab biosimilar MYL-1401O has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) as HER2 monotherapy. STUDY DESIGN: Here, we present the first real-world comparison of MYL-1401O vs RTZ as single/dual HER2-targeted therapy for the neoadjuvant, adjuvant, and palliative treatment of HER2-positive breast cancer in the first and second lines. METHODS: We retrospectively investigated medical records. We identified patients with HER2-positive early-stage breast cancer (EBC) (n = 159) who had received neoadjuvant chemotherapy with RTZ or MYL-1401O ± pertuzumab (n = 92) or adjuvant chemotherapy with RTZ or MYL-1401O plus taxane (n = 67) between January 2018 and June 2021, as well as patients with MBC (n = 53) who had received palliative first-line treatment with RTZ or MYL-1401O and docetaxel ± pertuzumab or second-line treatment with RTZ or MYL-1401O and taxane between January 2018 and June 2021. RESULTS: The rate of achieving pathologic complete response in patients receiving neoadjuvant chemotherapy was similar between those receiving MYL-1401O and RTZ (62.7% [37/59] and 55.9% [19/34], respectively; P = .509). Progression-free survival (PFS) at 12, 24, and 36 months was similar in the 2 cohorts of the EBC-adjuvant group: 96.3%, 84.7%, and 71.5%, respectively, in patients receiving MYL-1401O, and 100%, 88.5%, and 64.8% in patients receiving RTZ (P = .577). Median PFS was also similar in MBC, at 23.0 months (95% CI, 9.8-26.1) in patients receiving MYL-1401O and 23.0 months (95% CI, 19.9-26.0) in patients receiving RTZ (P = .270). The overall response rate, disease control rate, and cardiac safety profiles did not show significant differences in efficacy outcomes between the 2 groups. CONCLUSIONS: These data suggest that biosimilar trastuzumab MYL-1401O has similar effectiveness and cardiac safety to RTZ in patients with HER2-positive EBC or MBC.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study.

INTRODUCTION: Approximately 20-33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs' solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. RESULTS: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). CONCLUSIONS: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Clinical outcomes of patients with pure small cell carcinoma of the urinary bladder.

OBJECTIVES: There is not yet a standardized approach to treat patients with small cell carcinoma of the bladder (SmCCB). This study aims to investigate the clinical features, treatment, and survival outcomes of patients with pure SmCCB. MATERIALS AND METHODS: Patients diagnosed with SmCCB between January 2006 and September 2015 were retrospectively evaluated. RESULTS: A total of 34 patients with a median age of 63.0 years were included in the study, with a male to female ratio of 4.6:1.0. At the time of diagnosis, 22 patients (64.7%) had stage IV disease. At a median follow-up time of 12.7 months, 67.6% of patients died of bladder carcinoma, with an overall survival (OS) of 15.7 months for all patients. In the patients with stages I-III, nodal involvement, and distant metastases, the median OS was 31.8, 15.7, and 8.4 months, respectively (P = 0.005). Considering the survival rates of the patients (stages I-III) treated with surgery vs. local therapy, there was not a statistically significant difference (26.6 months and 31.8 months, P = 0.97, respectively). A multivariate analysis revealed that stage IV disease and poor ECOG performance status were associated with OS. CONCLUSION: The optimal treatment of SmCCB has been under debate. For the patients with advanced stage of disease (T4b, N+, M+), platinum containing chemotherapeutic agents should be preferred. Stage IV disease and poor ECOG performance status were associated with shorter OS.

The influence of post-diuretic late phase imaging in visual and quantitative evaluation of urothelial tumors by F-18 fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVE: Although F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a valuable imaging method in most of the malignant tumors, it is considered to have limited diagnostic ability in urothelial tumors due to high physiologic urine activity. The aim of the present study was to evaluate the effect of post-diuretic late phase imaging to the visual and quantitative evaluation of urothelial tumors in the staging and restaging of the patients. MATERIAL AND METHODS: Two patients with ureter and 40 patients with bladder tumors (6 females and 36 males, mean age: 67.12±8.79 years) who were referred for staging or restaging or treatment response evaluation to the F-18 FDG PET/CT were included in the study. Late phase (at the second hour after FDG injection) images including the renal pelvis and bladder region after the administration of approximately 40 mg furosemide were obtained after standard oncologic F-18 FDG PET/CT imaging. The images were evaluated by visual and quantitative interpretation, and index values were calculated. Paired samples T test was used to decide the significance of the difference between the early and late phase images. A p value <0.05 was considered significant. RESULTS: The activity accumulation in the primary or recurrent lesions in the bladder or ureter in the early and late phase images was statistically significantly different. Additionally, in 15/41 (37%) patients, the primary tumor in the bladder was only determined in late phase images, and additional lymph node metastases adjacent to the bladder or ureter were only observed in diuretic late phase images in some of the patients. The sensitivity, specificity, and diagnostic accuracy of the PET/CT with this methodology for N staging and M staging were 67%, 78%, and 82% versus 80%, 91%, and 82%, respectively. CONCLUSION: Late phase imaging after diuretic administration should be performed in case of non-visualization of primary tumor in the bladder region. The late phase post-diuretic imaging revealed significant improvement in the visual and quantitative diagnostic performance of the FDG PET/CT and has high diagnostic accuracy for the staging of urothelial tumors.

Prognostic factors of patients who received chemotherapy after cranial irradiation for non-small cell lung cancer with brain metastases: A retrospective analysis of multicenter study (Anatolian Society of Medical Oncology).

PURPOSE: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patient's survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. METHODS: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). RESULTS: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. CONCLUSION: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.

Calcitonin-negative neuroendocrine tumor of thyroid gland mimicking anaplastic carcinoma: an unusual entity.

Medullary thyroid cancer is the neuroendocrine tumor (NET) of thyroid with mostly both secreting calcitonin and immunohistochemically showing calcitonin positivity. Occasionally; NETs of thyroid may have little or no calcitonin expression. We present a case of serum calcitonin negative and immunohistochemically calcitonin-negative staining tumor with positive reaction to neuroendocrine markers synaptophysin and chromogranin-A. The patient's right vocal cord was paralytic and thyroid mass was huge with descending to thorax till hilar region. We discussed diagnostic difficulties and way of treatment about NETs of thyroid with the light of current literature with this case.

Survival analysis of biliary tract cancer cases in Turkey.

BACKGROUND: Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. MATERIALS AND METHODS: A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. RESULTS: The median overall survival was 19.3±3.9 months for all patients. The median disease free and overall survivals were 24.3±5.3 and 44.1±12.9 months in patients in which radical surgery was performed , but in those with with inoperable disease they were only 5.3±1.5 and 10.7±3.2 months, respectively. CONCLUSIONS: BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment.