Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Antibody-Drug Conjugates in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer. It is a heterogeneous breast cancer subtype with a poor prognosis. Given these negative features, there is a need for new treatment options beyond conventional chemotherapy in both the early stage and palliative setting. Impressive results have been reported with antibody-drug conjugates (ADCs) that link a cytotoxic payload to a monoclonal antibody, such as sacituzumab govitecan and trastuzumab deruxtecan, in the metastatic stage. The focus of this review is to discuss completed and ongoing trials involving ADCs in TNBC.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

The comparison of functional status and health-related parameters in ovarian cancer survivors with healthy controls.

PURPOSE: The primary purpose of this study was to evaluate functional status and health-related parameters in ovarian cancer (OC) survivors and to compare these parameters with healthy controls. The secondary purpose of this study was to compare these parameters in early and advanced OC survivors. METHODS: Thirty-two OC survivors (n = 15 early stage; n = 17 advanced stage) with no evidence/suspicion of cancer recurrence after completing adjuvant local and systemic treatments for at least 12 months and 32 healthy controls were recruited for functional- and health-related assessments. Participants were assessed using the following methods of measuring the following: 6-min walk test (6MWT) for functional exercise capacity, 30-s chair stand test (30 s-CST) for functional fitness and muscle endurance, a handheld dynamometer for peripheral muscle strength, and a handheld dynamometer for lower extremity strength, Medical Micro RPM for respiratory muscle strength, International Physical Activity Questionnaire-Short Form (IPAQ-SF) for physical activity level, and Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) for performance status, Checklist Individual Strength (CIS) for fatigue, Treatment/Gynecological Oncology-Neurotoxicity (FACT/GOG-NTX) for neuropathy, the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression level, and the World Health Organization-Five Well-Being Index (WHO-5) for generic quality of life. RESULTS: All OC survivors underwent surgery and chemotherapy, and only 9.4% received radiotherapy in addition to chemotherapy. The median recurrence-free period post-completion of adjuvant treatments was 24.00 (12.00-75.00) months. OC survivors had lower 6MWT (m) (p < 0.001, r = 1.50), peripheral muscle strength (p = 0.005, r = 0.72), knee extension (p < 0.001, r = 1.54), and respiratory muscle strength (maximal inspiratory pressure) (p < 0.001, r = 1.90) (maximal expiratory pressure) (p < 0.001, r = 1.68) compared to healthy controls. HADS-A (p = 0.005, r = 0.75) and CIS scores (p = 0.025, r = 0.59) were also higher in the OC survivors. Early-stage OC survivors had better 6MWT (m) than advanced-stage OC survivors (p = 0.005, r = 1.83). Peripheral muscle strength was lower in advanced-stage OC survivors (p = 0.013, r = 0.92). FACT/GOG-NTX scores were higher in early-stage OC survivors (p < 0.001, r = 1.42). No significant differences were observed between early- and advanced-stage OC survivors in other measures (p < 0.05). CONCLUSION: The findings suggest functional status, and health-related parameters are negatively affected in OC survivors. Additionally, higher levels of fatigue, neuropathy anxiety, and depression were reported in advanced OC survivors.

Triple Negative Breast Cancers: An Obsolete Entity?

Triple negative breast cancer is defined on the basis of what it is not. It has served as a useful umbrella entity for management of patients with breast cancer for the last couple of decades. However, during this period a number of novel therapies have become available. These therapies have been documented to be useful in subsets of TNBCs that can be identified on the basis of distinct biologic alterations. Herein we revisit the categorization and usage of the TNBC as an entity to assess its utility in view of the currently available therapies.

The Prognostic Nutritional Index (PNI): A New Biomarker for Determining Prognosis in Metastatic Castration-Sensitive Prostate Carcinoma.

Prognostic nutritional index (PNI), which is calculated using the albumin level reflecting nutritional status and lymphocyte count reflecting immune status, is useful in showing nutritional and immunological status related to survival and prognosis in many cancers. In this study, we aimed to evaluate the biomarker potential and effect of PNI in determining the prognosis of metastatic castration-sensitive prostate cancer (mCSPC). This retrospective observational study included the complete data of 108 patients with mCPSC who were treated for at least three months between 1 January 2010, and 1 June 2021. The relationships between cancer-specific survival (CSS), overall survival (OS), progression-free survival (PFS), and PNI were evaluated. The Kaplan-Meier method for OS, PFS, and CSS, as well as univariate and multivariate Cox regression models, were used for the statistical analyses. The median age of 108 patients included in the study was 68.54 (61.05-74.19) years. A value of 49.75 was determined to be the best cut-off point for the PNI. OS (months) was found to be significantly lower in patients with low PNI (median: 34.93, 95% CI: 21.52-48.34) than in patients with high PNI (median: 65.60, 95% CI: 39.36-91.83) (p = 0.016). Patients with high PNI (median: 48.20, 95% CI: 34.66-61.73) had significantly better CSS (months) than patients with low PNI (median: 27.86, 95% CI: 24.16-31.57) (p = 0.001). There was no statistically significant difference in PFS between patients with high PNI values (median: 24.60, 95% CI: 10.15-39.05) and patients with low PNI values (median: 20.03, 95% CI: 11.06-29.03) (p = 0.092). The PNI is a good predictor of OS and CSS in patients with mCSPC. The prediction of PFS, albeit showing a trend towards significance, was not statistically significant, probably due to the small number of cases.

The role of immune checkpoint inhibition in triple negative breast cancer.

INTRODUCTION: Immunotherapy has revolutionized cancer treatment, including TNBC, which has limited options of treatment and poor prognosis. ICIs studied in TNBC include pembrolizumab, nivolumab, atezolizumab, and durvalumab. Initial studies exploring ICI monotherapy demonstrated promising yet limited responses. Subsequent studies, KEYNOTE 522 and KEYNOTE 355, which combined ICI with chemotherapy, have resulted in the FDA approval of pembrolizumab in the early-stage and metastatic setting, respectively. AREAS COVERED: This article provides a comprehensive review of the role of ICI in the treatment of TNBC. We reviewed the trials that have evaluated ICI monotherapy, dual therapy, ICI in combination with chemotherapy, targeted therapy, vaccines and radiation. Additionally, we reviewed potential biomarkers of response and immune-related adverse events (irAEs). A literature search was conducted via PubMed and ClinicalTrials.gov as of 5 June 2023. EXPERT OPINION: Various approaches combining immunotherapy with chemotherapy, targeted therapy, vaccines and radiation have been assessed. Pembrolizumab remains the only ICI approved in both the early stage and mTNBC. The role of adjuvant pembrolizumab in those who achieved pCR after neoadjuvant therapy is being investigated. Combining ICI with PARP inhibitors and radiation shows promise. More research is needed in identifying predictors of response. Monitoring of irAEs remains crucial.

CDK4/6 Inhibition in the Metastatic Setting: Where Are We Headed?

OPINION STATEMENT: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER-2-) metastatic breast cancer (MBC) is the most common subtype of breast cancer. Due to therapeutic advances with molecularly targeted therapies, the prognosis for patients with metastatic disease has improved significantly. The advent of CDK4/6 inhibitors (CDK4/6i) has changed the treatment paradigm for patients with HR+HER2-MBC. CDK4/6i allowed for marked improvement in overall survival, delaying the time to chemotherapy initiation, and improved quality of life for our patients. Efforts are now focused on the best approach(es) for patients after progression on CDK4/6i. Can we further harness the benefit of CDK4/6i in novel combinations at the time of progression? Should we continue CDK4/6i or proceed other novel agents or endocrine therapies? As we advance our treatment strategies for HR+HER2-MBC, there is no longer a one-size-fits-all model, but instead a multifaceted and personalized approach lending to improved outcomes for our patients.

The effect of low HER2 expression on treatment outcomes in metastatic hormone receptor positive breast cancer patients treated with a combination of a CDK4/6 inhibitor and endocrine therapy: A multicentric retrospective study.

BACKGROUND: CDK4/6 inhibitors combined with endocrine therapy have significantly improved treatment outcomes for metastatic hormone receptor-positive (HR+) breast cancer patients. However, the impact of low HER2 expression on treatment response and progression-free survival (PFS) remains unclear. METHODS: This multicenter retrospective study included 204 HR+ breast cancer patients treated with a combination of CDK4/6 inhibitor and endocrine therapy. HER2-zero disease was detected in 138 (68%) and HER2-low disease in 66 (32%) patients. Treatment-related characteristics and clinical outcomes were analyzed, with a median follow-up of 22 months. RESULTS: The objective response rate (ORR) was 72.7% in the HER2 low group and 66.6% in the HER2 zero group (p = 0.54). Median PFS was not significantly different between the HER2-low and HER2 zero groups (19 months vs.18 months, p = 0.89), although there was a trend toward longer PFS in the HER2-low group for first-line treatment (24 months progression-free survival rate 63% vs 49%). In recurrent disease, the median PFS was 25 months in the HER2-low group and 12 months in the HER2-zero group (p = 0.08), while in de novo metastatic disease, the median PFS was 18 months in the HER2-low group and 27 months in the HER2-zero group (p = 0.16). The order of CDK4/6 inhibitor use and the presence of visceral metastasis were identified as independent variables affecting PFS. CONCLUSION: Low HER2 expression did not significantly impact treatment response or PFS in HR+ breast cancer patients treated with a CDK4/6 inhibitor and endocrine therapy. Because of the conflicting results in the literature, further prospective studies are needed to evaluate the clinical significance of HER2 expression in HR+ breast cancer.

The prognostic indicator in breast cancer treated with CDK4/6 inhibitors: the prognostic nutritional index.

Aims: The aim of this study was to evaluate the effect of prognostic nutritional index (PNI) on prognosis in patients with hormone receptor-positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitor + endocrine therapy. Methods: Patients receiving a CDK4/6 inhibitor were evaluated retrospectively. The PNI was calculated as: (10 × serum albumin [g/dl]) + (total lymphocyte count [×109/l] × 5). Results: In a study of 106 patients, a statistically significant survival advantage was observed in the high-PNI group over the low-PNI group (mean overall survival: 28.03 ± 0.487 months vs 22.46 ± 1.14 months; p = 0.013). Conclusion: For the first time in the literature, this study demonstrated the prognostic role of PNI in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors.

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.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

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.

Clinical outcomes of cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors in patients with male breast cancer: A multicenter study.

BACKGROUND: Since breast cancer is less common in men than in women, data on the use of new therapeutic agents, including cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors, are limited in patients with metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) male breast cancer. Therefore; we aimed to investigate the treatment responses of metastatic HR+, HER2-male breast cancer patients treated with CDK 4-6 inhibitors in a multicenter real-life cohort. METHODS: Male patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4-6 inhibitor, were included in the study. Demographic and clinical characteristics of the patients were recorded. We aimed to determine progression-free survival (PFS) time, response rates and drug related side effects. RESULTS: A total 25 patients from 14 institutions were recruited. The mean age at diagnosis was 57 years. Median follow-up was 19.53 (95% CI: 14.04-25.02) months. The overall response rate was 60%. While the median PFS was 20.6 months in the whole cohort, it wasn't reached in those using CDK 4-6 inhibitors in first line and 10 months in the subsequent lines (p:0.009). No new adverse events were encountered. CONCLUSION: In our study, we found that CDK 4-6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4-6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.

CD47 (don't eat me signal) expression levels and its relationship with clinicopathologic features in early-stage prostate carcinoma.

BACKGROUND: Prostate cancer is a cancer with poor host immune response and could be defined as a non-T-cell inflamed tumor. Therefore, immunotherapy treatments could not be included in the treatment of prostate cancer until recently. Inadequate antitumoral response is one of the main reasons why tumor cells multiply rapidly and cause lethal results. It was shown that CD47 molecule, which is secreted at high levels by leukemia cells, reduces macrophage-mediated phagocytosis and thus facilitates escape from the antitumoral immune response. The aim of this study was to show don't eat me signaling in prostate carcinoma tissues and its relationship with macrophage polarization. MATERIALS AND METHODS: A total of 263 patients with a diagnosis of prostatic adenocarcinoma after radical prostatectomy between 2015 and 2020 at our institute were included in the study. CD47, CD68, and CD163 expression levels were examined immunohistochemically (IHC) in these tissues. The relationship of these expression levels with unfavorable prognostic factors and survival for prostate carcinoma was investigated. RESULTS: In this study, all the operated prostate carcinoma cases had CD47 expression in tumor tissue, but only 52.5% had a high level of expression. Of 263 prostate cancer tissues, 135 (51.3%) showed high expression of CD68 protein and 189 (71.9%) showed high expression of CD163 protein. There was a statistically strong relationship between CD47, CD68, and CD163. CONCLUSIONS: The CD47 molecule is basically a molecule that inhibits macrophage activation. CD68 is mostly used for macrophage classification, while CD163 is used for tumor-associated macrophage classification. Unlike others, we IHC examined CD47, CD68, and CD163 expressions in the surgical materials of patients who were operated for prostate carcinoma. In addition, we concluded that strong CD47 expression was closely associated with strong CD68 and CD163 expression in all tumor samples. However, a significant relationship between these expression levels and survival could not be demonstrated.

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.