Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce. OBJECTIVE: We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey. PATIENTS AND METHODS: This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024. RESULTS: The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months. CONCLUSIONS: In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

Concomitant Use of Ado-trastuzumab Emtansine and Imatinib in a Patient of CML and Metastatic Breast Cancer.

Imatinib is a CYP3A4 inhibitor, while ado-trastuzumab is a CYP3A4 substrate. Imatinib can interact with ado-trastuzumab emtansine (T-DM1) and can increase T-DM1 concentrations, leading to T-DM1-related toxicity. There is no trial or case report in the literature on the concomitant use of Imatinib and T-DM1. Herein, we report a case in which T-DM1 was used effectively with imatinib in a patient with chronic myeloid leukaemia (CML) and metastatic Her-2-positive breast cancer. A 37-year female using imatinib for CML was diagnosed with breast cancer and a modified radical mastectomy was performed. Skin metastasis occurred within one year after adjuvant therapy was completed. Lung metastasis occurred after Trastuzumab + vinorelbine treatment and T-DM1 and imatinib were given to the patient. No side effects were observed except for grade 1 fatigue. This case report is the first to report the concomitant use of T-DM1 and imatinib in a patient of CML and metastatic breast cancer. Key Words: Imatinib, Ado-trastuzumab emtansine, Breast cancer, Chronic myeloid leukaemia.

Immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy.

Aim: To evaluate the immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy. Methods: This multicenter, prospective, observational study was conducted with 47 patients receiving active systemic therapy for cancer. CoronaVac was administered as two doses (3 µg/day) on days 0 and 28. Antibody level higher than 1 IU/ml was defined as 'immunogenicity.' Results: The immunogenicity rate was 63.8% (30/47) in the entire patient group, 59.5% (25/42) in those receiving at least one cytotoxic drug and 100% (five of five) in those receiving monoclonal antibody or immunotherapy alone. Age was an independent predictive factor for immunogenicity (odds ratio: 0.830; p = 0.043). Conclusion: More than half of cancer patients receiving active systemic therapy developed immunogenicity.

Tolvaptan treatment in hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): effects on survival in patients with cancer.

PURPOSE: To investigate the clinical outcomes of patients with hyponatremia who received supportive treatment or tolvaptan plus supportive treatment and the effects of treatment and other variables on overall survival METHODS: This study included oncology patients who were hospitalized at two oncology centers between January 1, 2016 and December 31, 2019 for hyponatremia (sodium levels < 135 mEq/L) and who received tolvaptan plus supportive treatment (n = 22) or supportive treatment only (n = 42). RESULTS: The median age of all the patients was 59 years (range 26-85) and 64.1% of the patients were male. There was no statistically significant difference between patients in the tolvaptan plus supportive treatment (TpST) group and the supportive treatment only (ST) group in terms of gender and age (p > 0.05). In the TpST group, recovery days of the hyponatremia after treatment and the length of hospital stay was shorter and hyponatremia symptoms and hospital complications were less frequent compared to the ST group (p < 0.05). There was no significant difference between the TpST group and the ST group in terms of overall survival (OS). OS was shorter in men who were non-responders to hyponatremia treatment and had recurrent hyponatremia. Multivariable analysis showed that normal sodium levels after treatment decreased the risk of death. CONCLUSION: In the treatment of hyponatremia in cancer patients, TpST was found to have more positive effects on blood sodium levels, length of hospital stay, hospital complications, and hyponatremia symptoms compared to ST. A decreased risk of death was observed in patients with normal sodium levels after treatment.

Clinical features of metaplastic breast carcinoma: A single-center experience.

AIM: Metaplastic breast cancer (MBC) is a rare subtype with unusual clinical features. We aimed to analyze treatment results and define patients' characteristic features in our large MBC patient series. MATERIALS AND METHODS: Fifty-six patients with early MBC who received adjuvant radiotherapy (RT) in our center were included in the study. The age, sex, subtypes of MBC, histopathology, hormone and nodal status, tumor size, and types of treatment were retrospectively provided from hospital records. RESULTS: The median tumor size was 4 (1.3-16.5) cm, and triple-negative MBC cases were 38 (67.8%) of all patients. Axillary nodal involvements were present in 25 (44.6%) patients. The median follow-up time was 45.8 (4.9-130) months; the overall survival (OS) and disease-free survival (DFS) for 5 years were 67% and 64%, respectively. While distant metastases were seen in 15 (26.7%) patients, local recurrences were seen in only 4 patients. The median OS and DFS were higher in patients with ≤5.2 cm tumor than >5.2 cm ([130 vs. 49 months, P = 0.01] and [130 vs. 30 months, P = 0.009], respectively). Nodal involvement, hormone receptor status, surgical treatment, and type of RT had no effect on survival. In multivariate analysis, tumor size was not an independent prognostic factor for OS (P = 0.068; hazard ratio [HR]: 3.4, 95% confidence interval [CI] = 0.91-12.8), whereas age >65 years was found an independent poor prognostic factor for OS ([HR: 4.25, 95% CI: 0.23-0.78, P = 0.021] and DFS [HR: 3.1, 95% CI: 0.02-0. 87; P = 0.04], respectively). CONCLUSIONS: Distant metastasis is at the forefront rather than local recurrence in MBC patients. More studies are needed to determine the factors that affect survival independently in MBC.

Systemic Immune-inflammation Index is the Best Prognostic Factor in Patients with Advanced Stage Adenocarcinoma of the Lung Treated with Pemetrexed.

OBJECTIVE: To evaluate the prognostic role of systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in patients who received platin-pemetrexed combination therapy and/or maintenance pemetrexed therapy. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, HSU Dr. Abdurrahman Yurtaslan Oncology, Training and Research Hospital, Turkey, between January 2010 and March 2020. METHODOLOGY: Data of patients with metastatic adenocarcinoma of lung, who underwent platin-pemetrexed combination therapy and/or maintenance pemetrexed therapy retrospectively, were evaluated. Patient characteristics and disease parameters were recorded. Moreover, NLR, PLR, and SII were calculated. Survival analysis with the Kaplan-Meier and Log-rank test was performed. Cox regression analysis was used to determine independent prognostic factors of overall survivall (OS) and progression-free survival (PFS). RESULTS: In the univariate analyses, NLR-low group and SII-low group had significantly longer PFS compared to NLR-high and SII-high groups (10 months vs. 8 months, p=0.018, and 13 months vs. 8 months, p<0.001, respectively). The significant differences were seen between SII-low and SII-high groups for OS (24 months vs. 13 months, p=0.001). In multivariate analyses, response to treatment and low-SII were independent prognostic factors for PFS (HR: 0.25, p<0.001, and HR: 0.47, p=0.002, respectively) and OS (HR: 2.09, p=0.001, and HR: 2.05, p=0.001, respectively).   Conclusion: SII is the most powerful of the three studied inflammatory indices, which could independently predict overall and progression-free survival. Key Words: Systemic immune-inflammation index, Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Adenocarcinoma, Lung cancer, Pemetrexed.

Enzalutamide Treatment in Metastatic Castration-resistant Prostate Cancer: Before and after Docetaxel.

ABSTRACT  Objective: To evaluate the efficacy and safety of enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) in docetaxel-naive and docetaxel-pretreated patients. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: HSU Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey, from March 2017 to July 2019. METHODOLOGY: A total of 67 patients with mCRPC were retrospectively evaluated. Castration-naive patients and non-metastatic patients were excluded from the study. Comorbid diseases, ECOG performance status, PSA response, and the radiological response of the patients were recorded. Kaplan-Meier method was used for survival analysis, and a Cox regression model was formed. RESULTS: The overall survival (OS) was significantly longer in patients with eastern cooperative oncology group performance status (ECOG PS) 0 (26.0 vs. 14.0 months, p=0.031), PSA response (26.0 vs. 7.0 months, p=0.002), radiological response (26.0 vs. 10.0 months, p=0.006) and duration of enzalutamide ≥9 months (26.0 vs. 7.0 months, p<0.001) compared to ECOG PS 1. According to Cox regression analysis, patients with PSA response had 0.35 fold (CI.95% 0.13-0.94) reduced the risk of death and 0.36-fold (CI.95%0.16-0.85) reduced the risk of progression compared to those without PSA response. Moreover, longer enzalutamide treatment (≥9 months) was noted to decrease the risk of death. CONCLUSION: PSA response, radiological response and duration of enzalutamide treatment may predict the improvement of survival in patients with mCRPC treated with enzalutamide.   Key Words: Enzalutamide, Docetaxel, Castration-resistant prostate cancer, Overall survival, Progression-free survival.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

Prognostic Importance of Metastatic Site in Intermediate-risk Group Metastatic Renal Cell Cancer Treated with Tyrosine Kinase Inhibitors.

OBJECTIVE: To determine the prognostic importance of the metastatic site in metastatic renal cell cancer (mRCC) patients in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate-risk. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey, from January 2010 to November 2018. METHODOLOGY: Records of 113 mRCC patients, determined to be in the intermediate-risk group according to IMDC criteria, were reviewed retrospectively. All patients used a tyrosine kinase inhibitor - sunitinib or pazopanib - for metastatic disease. Patients' records included age, gender, metastatic site, number of metastases and treatment regimen. The Kaplan-Meier method was used for survival analysis, and a Cox regression model was formed. RESULTS: The median age of the patients was 58 years (Q1 - Q3: 44 - 66 years) and 87.6% of the patients had ≥2 metastatic sites. The most common metastatic sites were the lung (51.3%), lymph nodes (26.5%), bone (26.5%) and brain (17.7%). Median overall survival (OS) was shorter in the patients with bone and brain metastasis than in those without (15.0 months vs. 21.0 months, p = .026 and 14.0 months vs. 21.0 months, p = .009, respectively). Multivariate analysis showed that brain and bone metastasis were independent prognostic risk factors (HR: 2.43, p = .017 and HR: 2.10, p = .042, respectively). CONCLUSION: Bone and brain metastasis had a negative effect on OS in IMDC intermediate-risk group mRCC patients. Key Words: Metastatic site, Brain metastasis, Bone metastasis, Renal cell carcinoma, Prognosis.

A case of pelvic giant cell tumor of bone, complete remission with denosumab: long duration of response.

Although giant cell tumor of bone has been considered as a disease with benign course, it can lead to bone destruction and serious morbidity. A 19-year-old case was presented with hip pain. There was a recurrence after 9 months of curative surgical resection and zoledronic acid use, and as surgical morbidity would be high, antiosteoclastic receptor activator of nuclear factor kappa B ligand inhibitor denosumab treatment was administered. She had a complete remission after 18 months of denosumab treatment. The important point in the present case is that it has been followed up without recurrence after around 42 months of denosumab use and 11 months of follow-up after the cessation of drug. In recurrent cases in which nonmetastatic surgery is not suitable, the use of denosumab decreases tumor progression. The duration of use in unresectable and advanced cases still remains unclear.