Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study).

INTRODUCTION: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. MATERIALS AND METHODS: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. RESULTS: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. CONCLUSION: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

The evaluation of doxorubicin-induced cardiotoxicity: comparison of Doppler and tissue Doppler-derived myocardial performance index.

BACKGROUND: Doxorubicin is a chemotherapeutic agent used in a wide spectrum of cancers. However, cardiotoxic effects have limited its clinical use. The early detection of doxorubicin-induced cardiotoxicity is crucial. The purpose of our study was to assess values of Doppler and tissue Doppler imaging (TDI)-derived myocardial performance index (MPI) in adult cancer patients receiving doxorubicin treatment. METHODS: A total of 45 patients underwent echocardiographic examinations before any doxorubicin had been administered and then after doxorubicin. Doppler and TDI-derived MPI of left ventricular (LV) were determined in the evaluation of cardiotoxicity. Additionally, TDI-derived MPI of right ventricular (RV) was determined. RESULTS: All patients underwent control echocardiographic examination after mean 5 ± 1.7 months. The LV MPI obtained by both Doppler and TDI were increased after doxorubicin treatment (0.56 ± 0.11, 0.61 ± 0.10, p = 0,005 vs 0.51 ± 0.09, 0.59 ± 0.09, p = 0.001, respectively). There was no correlation between Doppler-derived MPI and cumulative doxorubicin dose (coefficient of correlation 0.11, p = 0.6). TDI-derived MPI was correlated with cumulative doxorubicin dose (coefficient of correlation 0.35, p = 0.015), but this correlation is weak (r = 0.38). The study population was divided into two groups according to doxorubicin dose (below and above 300 mg level). There was a moderate correlation between TDI-derived MPI and less than 300 mg of doxorubicin dose (coefficient of correlation 0.51, p = 0.028). However, Doppler-derived MPI was not correlated with less than 300 mg of doxorubicin dose (coefficient of correlation 0.38, p = 0.123). Also, there was no significant change in the TDI-derived RV-MPI (0.49 ± 0.14, 0.50 ± 0.12, p = 0.56). CONCLUSIONS: TDI-derived MPI is a useful parameter and an early indicator compared with Doppler-derived MPI in the detection of cardiotoxicity during the early stages. Also, doxorubicin administration does not affect RV function.

The acute effect of tropisetron on ECG parameters in cancer patients.

OBJECTIVES: The 5-hydroxytryptamine 3 receptor antagonists, including tropisetron, ondansetron, granisetron, and dolasetron are agents used effectively for supportive care. They are used for the prevention and treatment of chemotherapy and radiotherapy-induced emesis. Despite their overall excellent safety profile, some electrocardiographic changes related to heart rate and repolarization were reported. Ondansetron, granisetron, and dolasetron were studied on this manner. But to our knowledge, there is no information about the cardiac side effects of tropisetron. In this study, we aimed to determine the acute effects of tropisetron on ECG parameters related to repolarization, heart rate, and systemic blood pressure. MATERIALS AND METHODS: Fifty-five cancer patients who received tropisetron for the prevention of acute chemotherapy-induced nausea and vomiting were enrolled into this single center, prospective study. Standard 12-lead ECG recordings were performed at baseline and 30 min after tropisetron (5 mg given over 1 min IV bolus) administration. P wave durations and corrected QT intervals were measured; P wave dispersion and QTc dispersion were calculated. RESULTS: In comparison with baseline, mean heart rate significantly decreased 30 min after administration of tropisetron. Tropisetron did not result in a significant change in P wave duration, corrected QT interval, P dispersion, and QTc dispersion. CONCLUSION: In this study, tropisetron did not show any ventricular and atrial arrhythmogenic effect because of repolarization abnormalities. Only it may cause a slight decrease in heart rate.

The acute effect of trastuzumab infusion on ECG parameters in metastatic breast cancer patients.

OBJECTIVES: Although trastuzumab therapy is known to be associated with congestive heart failure, its arrhythmogenic potential has not been studied in detail. The purpose of this study was to determine the acute influence of trastuzumab infusion on electrocardiogram (ECG) parameters in patients with metastatic breast cancer. PATIENTS AND METHODS: Twenty patients with HER2 overexpressing metastatic breast cancer and normal cardiac function were enrolled in this single-centre prospective study. Standard 12-lead ECG recordings were performed at baseline and after trastuzumab infusion (2 mg/kg given over 30 min). P-wave durations, QT and RR intervals were measured and QT dispersion (QTd) and P-wave dispersion (Pd) were calculated. RESULTS: In comparison with baseline, no statistically significant change in any ECG parameters, including QT and RR intervals, P wave durations, Pd and QTd, was observed after infusion of trastuzumab. CONCLUSION: In this study, no abnormality of atrial and ventricular depolarisation and repolarisation, indicated by Pd and QTd, was detected after infusion of trastuzumab. As Pd and QTd are both known to be associated with increased risk of serious arrhythmias and sudden death, it would appear that trastuzumab has no acute arrhythmogenic potential related to cardiac depolarisation and repolarisation.