Efficacy and safety of G-CSF prophylaxis in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy.

OBJECTIVES: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). METHODS: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. RESULTS: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). CONCLUSION: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

Effect of HER2-low status on brain metastasis-free survival and survival after brain metastasis in patients with breast cancer.

AIMS AND OBJECTIVES: The discovery of novel human epidermal growth factor receptor 2 (HER2)-directed antibody‒drug conjugates has accelerated the identification of the HER2-low subtype. However, the biological significance of low HER2 expression in breast cancer brain metastasis (BCBM) is unclear. METHODS: Patients with HER2-negative BC and brain metastasis were retrospectively screened between February 2012 and November 2023. Brain metastasis-free survival (BMFS) and survival after brain metastasis (SABM) were analyzed according to HER2 expression. RESULTS: A total of 201 female patients, 84 of whom were HER2-low and 117 of whom were HER2-zero, were evaluated. The median BMFS in the entire cohort was 35.6 months (95% CI 29.8-41.4). Although HER2-low patients had numerically longer median BMFS than HER2-zero patients (43.7 m vs. 30.1 m, p = 0.025), multivariate analysis revealed that the difference was not significant (p = 0.167). BMFS between the HER2-low and HER2-zero groups was similar in the hormone receptor (HR)-positive (52.8 m vs. 47.6 m, p = 0.276) and HR-negative (15.3 m vs. 19.7 m, p = 0.930) cohorts. The median SABM in the entire cohort was 6.0 months (95% CI 3.8-8.1). HER2-low and HER2-zero patients had similar median SAMB (5.4 m vs. 6.1 m, p = 0.816). The SABM between the HER2-low and HER2-zero groups was similar in the HR-positive (6.3 m vs. 8.7 m, p = 0.375) and HR-negative (3.3 m vs. 4.2 m, p = 0.783) cohorts. CONCLUSIONS: Low HER2 expression does not affect BMFS or SAMB in brain metastatic breast cancer patients in this real-world population.

Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study.

PURPOSE: In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. METHOD: The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. RESULTS: One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. CONCLUSION: This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment.

Trastuzumab-induced optic neuritis: "blindness" side effect.

INTRODUCTION: Trastuzumab improved the prognosis of patients with human epidermal growth factor receptor 2 (HER2)+ breast cancer (BC). Here, we present a patient who developed acute vision loss due to optic atrophy in both eyes after trastuzumab. CASE REPORT: A 60-year-old female patient was diagnosed with locally advanced HER2+ BC in January 2021. After four cycles of neoadjuvant anthracycline-based chemotherapy followed by four cycles of docetaxel, trastuzumab, and pertuzumab combined treatment, the patient underwent a right modified radical mastectomy. Three days after the end of the second cycle of adjuvant trastuzumab, she presented with acute vision loss. The patient's visual acuity was 90% in the right eye and 60% in the left eye. The left eye had optic nerve edema and spindle hemorrhages. First, on suspicion of optic neuritis, the patient was given a 1 gram/day pulse steroid for three days. However, optic neuritis was not considered during the follow-up. Metastasis was considered at the exit of the left optic nerve. Trastuzumab was started by making a mutual decision with the patient. Six days after the sixth dose of adjuvant trastuzumab, she presented with almost complete vision loss. MANAGEMENT AND OUTCOME: The patient was diagnosed with optic neuritis, and a pulse steroid was administered. Trastuzumab was permanently discontinued. However, the patient's visual acuity in both eyes remained at 5-10%. DISCUSSION: Vision loss due to optic neuritis is a devastating side effect. Understanding that trastuzumab-induced optic neuritis may develop will help clinicians detect side effects early and manage them more effectively.

Investigation of Clinical Course and Possible Drug Interactions in Patients with Multiple Sclerosis and Breast Cancer.

This study aims to investigate the clinical course and potential drug interactions of breast cancer patients diagnosed with multiple sclerosis (MS). Ten patients diagnosed with MS and breast cancer, who were followed up and treated in the authors' centre between January 2000 and December 2020, were retrospectively scanned from the Hospital's electronic registry system and included in the study. The patients' age, gender, history of MS diagnosis, drugs used, date of breast cancer diagnosis, stage at diagnosis, pathological features, treatment information, surgery types, recurrence or metastasis history and regions, and side effects observed during anticancer treatment were recorded. Key Words: Multiple sclerosis, Breast cancer, Drug-drug interactions.

Triglyceride-Glucose Index: A Candidate Prognostic Marker in HR-Positive/HER2-Negative Metastatic Breast Cancer Patients Treated With CDK4/6 Inhibitors.

AIMS AND OBJECTIVES: Although cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) are a vital part of the treatment of hormone receptor (HR)-positive/HER-2-negative metastatic breast cancer (BC), individuals have different sensitivities to CDK4/6i, indicating the need for biomarkers. The fasting triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance (IR). Herein, we investigated the prognostic significance of the fasting triglyceride glucose (TyG) index in HR+/HER2- metastatic BC patients treated with CDK4/6i plus endocrine therapy (ET). METHODS: About 333 patients with HR+/HER2-metastatic BC treated with CDK4/6i plus ET were analyzed retrospectively. The TyG index was calculated within 3 months before the initiation of CDK4/6i plus ET. The median value of 8.43 was taken as the cutoff for the TyG index. RESULTS: The median overall survival (OS) was 73.6 months (95% CI, 66.0-81.1) in the whole cohort. The progression-free survival (PFS) was significantly longer in the low-TyG subgroup than in the high-TyG subgroup (30.1 vs. 21.3 months, multivariate adjusted [HR] = 0.666, 95% CI, 0.450-0.987, P = .043). While the median OS was not reached in the low TyG subgroup, it was 69.0 months in the high TyG subgroup (multivariate-adjusted HR = 0.513, 95% CI, 0.281-0.936, P = .030). Although the ORR and DCR were numerically greater in the low-TyG subgroup, no significant differences were observed between the low-TyG subgroup and high-TyG subgroup (28.1% vs. 24.7%, P = .476; 83.2% vs. 80.1%, P = .463, respectively). CONCLUSIONS: These data imply that the TyG index could be a predictive biomarker for the therapeutic efficacy of CDK4/6is. Extensive prospective studies are needed to confirm these findings.

Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study.

AIM: HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer. METHODS: A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed. RESULTS: The median age was 64 (24-83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36-27.58), and in the low ratio group was 16.17 months (95% CI: 10.95-21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02-28.37) in the high HER2 gene copy number group and 10.13 months (5.55-14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55-14.33) in the group with high HER2 gene copy number and 7.56 months (4.62-10.49) in the low copy number group (p = 0.06). CONCLUSION: Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.

Comparison of homologous and heterologous inactivated and mRNA vaccination programme against SARS-CoV-2 in dialysis patients.

AIM: To evaluate the vaccine response and the effect of the booster dose on COVID-19 positivity in haemodialysis (HD) and peritoneal dialysis (PD) patients who received and did not receive BNT162b2 as a booster dose after two doses of CoronaVac. METHODS: The study included 80 PD and 163 HD patients, who had been administered two doses of the CoronaVac. Antibody levels were measured on Days 42 and 90 after the first dose. Measurements were repeated on Day 181 after the first dose in the patients that received two vaccine doses and on Day 28 after the third dose in those that also received the booster dose. Antibody levels below 50 AU/mL were considered negative. RESULTS: The seropositivity rate was similar in the HD and PD group on Days 42 and 90 (p = 0.212 and 0.720). All patients were seropositive in the booster group. The antibody level was lower in the patients that received CoronaVac as the booster compared to those administered BNT162b2 in HD and PD groups (p < 0.001 and 0.002). COVID-19 positivity was detected in 11 patients (7 = had not received the booster dose, 4 = had received third dose of CoronaVac). The multivariate analysis revealed that as age increased, COVID-19 positivity also increased (OR: 1.080, 95% CI: 1.017 - 1.146, p = 0.012), while booster dose administration decreased this positivity (OR: 0.113, 95% CI: 0.028 - 0.457, p = 0.002). CONCLUSION: Our results may indicate the need for additional vaccination doses in patients with HD and PD. Our findings indicate a higher antibody response in dialysis patients with heterologous BNT162b2 as a booster dose after two doses of CoronaVac compared to homologous CoronaVac.

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Prognostic factors in non-metastatic HER2 'low' and HER2 'negative' breast cancer: single institute experience.

AIM: Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer. MATERIAL AND METHODS: In a retrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. A total of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group. RESULTS: The HER2 low group had significantly longer 5­year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5­year DFS. CONCLUSION: Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients.

Higher TP53 somatic mutation prevalence from liquid biopsy analysis in ever smoker non-small-cell lung cancer patients.

OBJECTIVE: Cigarette smoking is a primary risk factor, linked to 80% of LC deaths. TP53, a key gene, is implicated in various cancers, with TP53 alterations in 36.7% of cancers. This research aims to investigate TP53 mutations detected in NSCLC patients by liquid biopsy and explore the relationship between these mutations and smoking history. MATERIAL AND METHOD: The study enrolled a total of 340 patients diagnosed with non-small cell lung cancer (NSCLC). For sequencing, the Illumina NextSeq 500 system was utilized. The oncogenicity of the variants was assessed according to the ClinGen/CGC/VICC SOP and the variants were categorized into four tiers according to AMP/ASCO/CAP. RESULTS: The most common mutations were in TP53 (48.7%), followed by EGFR, PIK3CA, and PTEN. Missense mutations were frequent, with TP53 and EGFR having higher rates in ever-smokers. No indels or complex mutations were found in ever-smokers. Patient age ranged from 20 to 86 years. Tier I-II variants were more common in ever-smokers, while Tier III variants were prevalent in never-smokers. TP53 mutations were more frequent in ever-smokers, showing a strong association with smoking. Domain distribution showed differences in PIK3CA. Transversion/transition ratios varied by gene and smoking status. DISCUSSION: The presence of TP53 mutations is strongly associated with both cigarette smoking and elevated Tv/Ti ratios. The tier status of TP53, EGFR, and PTEN variants does not show a specific domain distribution, but interesting associations are observed between the tier status and domain distribution in PIK3CA variants. Therefore, further comprehensive investigations are needed to explore this entity, as well as the underlying factors contributing to the increased Tv/Ti rates in the TP53 gene. Such research will provide deeper insights into the genetic alterations associated with smoking and tumor heterogeneity, ultimately aiding in the development of targeted therapies.

Efficacy of adjuvant CDK4/6 inhibitors in hormone receptor-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: The combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and standard endocrine therapy (ET) in the adjuvant treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) has yielded conflicting results. We performed a pooled analysis of the adjuvant efficacy of CDK4/6 inhibitors by including data from the NATALEE trial, the most recent trial on this topic. METHODS: We searched major databases and congress proceedings until 7 June 2023 to identify randomized controlled trials (RCT) comparing adjuvant CDK4/6 inhibitor plus ET combination versus ET in HR-positive/HER2-negative early-stage BC. RESULTS: Four RCTs involving a total of 17,749 patients were included. According to the pooled analysis of these four studies, significant improvement in invasive disease-free survival (iDFS) was observed with the addition of CDK4/6 inhibitors to standard ET (HzR: 0.81, 95% CI 0.67-0.97). IDFS benefit was irrespective from menopausal status, Ki-67 index, tumor grade, and previous chemotherapy. CDK4/6 inhibitors plus ET had a significant improvement in iDFS in stage 3 whereas there was a trend toward better iDFS in stage 2 (HzR for stage 3: 0.67, 95% CI 0.58-0.78; HzR for stage 2: 0.74, 95% CI 0.55-1.01). CONCLUSIONS: Addition of CDK4/6 inhibitors to standard ET in the adjuvant treatment of HR-positive/HER2-negative early-stage BC improves iDFS.

Adjuvant Capecitabine after Neoadjuvant Chemotherapy in Triple Negative Breast Cancer with Lymph Node Metastasis.

OBJECTIVE: To evaluate the effect of complete pathological response (pCR) on prognosis in patients with axillary lymph node-positive triple-negative breast cancer (TNBC) and the efficiency of adjuvant capecitabine. STUDY DESIGN: Analytical study. Place and Duration of the Study: University of Health Sciences, Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, between March 2015 and December 2021. METHODOLOGY: The study included 92 patients with TNBC with enlarged axillary lymph nodes and treated with neoadjuvant chemotherapy. The patients were classified as those with and without postoperative pCR and compared in terms of survival. Subsequently, the patients who did not achieve pCR were classified as receiving and not receiving adjuvant capecitabine and were compared for DFS (disease-free survival) and OS (overall survival). Parameters that showed statistical significance were re-evaluated with Cox regression analysis. RESULTS: The 5-year DFS rate was 84.3% in those who achieved pCR, while it was 55.1% in those who did not (p=0.026). The 5-year OS rate was 82.8% in the pCR arm, while it was 51.0% in the non-pCR arm (p=0.070). The 5-year DFS rate was 66.3% in adjuvant capecitabine-receiving patients, while it was 40.8% in the non-capecitabine arm (HR=0.40, p=0.031). The 5-year OS rate was 68.9% in adjuvant capecitabine-receiving patients, while it was 29.6% in the non-capecitabine arm (HR= 0.40, p=0.062).  Conclusion: Obtaining pCR following NAC in a locally advanced TNBC is an independent prognostic marker for DFS and OS. In the presence of residual disease, improvement in DFS and OS with adjuvant capecitabine was demonstrated by the real-life data. KEY WORDS: Triple-negative breast cancer, Neoadjuvant chemotherapy, Capecitabine, Survival.

The Effect of HER2-Low Status on Pathological Complete Response and Survival in Triple-Negative Breast Cancer: A Systemic Review and Meta-Analysis.

This meta-analysis conducted a comprehensive analysis of research investigating the correlation between HER2 expression levels and treatment outcomes in early-stage triple-negative breast cancer (TNBC) patients. We systematically searched major databases for studies published up to January 01, 2023. The data from various studies examined the relationship between HER2-zero and HER2-low tumors in terms of pathological complete response (pCR) rates, disease-free survival (DFS), and overall survival (OS) outcomes. The odds ratio (OR) and 95% confidence interval (CI) by the number of events were calculated using the Mantel-Haenszel method to analyze pCR. The hazard ratio and 95% CI were calculated using the inverse variance method for DFS and OS. In all comparisons, I2 was 0% and no heterogeneity was detected. A total of 12 retrospective studies involving 4094 patients were included. Thirty-six percent of the patients were in the HER2-low group. All 12 studies were included in the pooled analysis for pCR, and there was no difference between HER2-zero and HER2-low (40% vs. 38%, respectively; pooled OR:1.01 95% CI 0.88-1.16; I2: 0%). Four studies were included in the pooled analysis for DFS and 3 in the OS analysis. DFS and OS were significantly better in the HER2-low group (pooled hazard ratio: 0.67 for DFS, 0.64 for OS). There was no difference between HER2-low and HER2-zero in terms of pCR in early-stage TNBC. However, HER2-low was found to be associated with prolonged DFS and OS. PROSPERO REGISTRATION NUMBER: CRD42023391002.

Percutaneous ablation treatment in metastatic lung tumors: a single-center experience.

BACKGROUND: In recent years, many studies have proven that percutaneous thermal ablation is an effective second-line treatment method with low complication rates in early-stage non-small cell lung carcinoma and lung metastases. Radiofrequency ablation and microwave ablation are commonly used for this purpose. PURPOSE: To evaluate the factors affecting the success of the percutaneous thermal ablation treatment with technical success, complication rates, and long-term follow-up results in metastatic lung lesions. MATERIAL AND METHODS: Computed tomography (CT)-guided percutaneous ablation was performed for 70 metastatic lung lesions in 35 patients (22 men, 13 women; mean age = 61.34 years; age range = 41-75 years). Radiofrequency ablation was performed in 53/70 (75.7%) lesions and microwave ablation in 17/70 (24.3%) lesions. RESULTS: The technical success rate was 98.6%. Median overall survival, progression-free survival, and local recurrence-free survival of the patients were 33.9 months (range=25.6-42.1 months), 12 months (range=4.9-19.2 months), and 24.2 months (range=8.2-40.1 months), respectively. One- and two-year overall survival rates were 84% and 74%, respectively. Median progression-free survival times were 20.3 months and 11.4 months, respectively, according to the number of metastatic lung lesions being single and multiple, and the difference was statistically significant (P = 0.046). According to the number of lesions ≤3 and >3, the difference was also found statistically significant (P = 0.024) (14.3 months and 5.7 months, respectively). CONCLUSION: In conclusion, CT-guided percutaneous thermal ablation is a safe and effective treatment method in metastatic lung lesions. The number of lesions is the most important factor in predicting treatment success.

FOLFIRI-bevacizumab-induced acute toxic leukoencephalopathy.

INTRODUCTION: Acute toxic leukoencephalopathy (ATL) is a rare complication of cancer treatment, with symptoms varying from mild cognitive impairment to coma. Recognition and management of ATL are important because in most cases, the cessation of the responsible agent is essential. CASE REPORT: We report a case of a 57-year-old male with relapsed right colon cancer who had multiple steps of chemotherapy, admitted to the emergency department (ED) with confusion and inability to talk, 4 days after FOLFIRI and bevacizumab treatment. To exclude cerebrovascular events cranial computed tomography and diffusion-weighted magnetic resonance imaging were evaluated. There was bilateral and symmetric diffusion restriction on white matter, which was consistent with ATL. MANAGEMENT AND OUTCOME: Supportive treatment such as optimization of blood pressure and metabolic control was applied since there is no specific treatment for ATL other than cessation of the responsible agents. 12 days after the admission to the ED his neurologic symptoms were normalized and there was no diffusion restriction on control imaging. DISCUSSION: ATL is a rare complication of cancer treatment and responsible agents are increasing in number due to the development of cancer treatment. ATL is associated with drugs that are used frequently such as 5-fluorouracil. ATL is mostly reversible, but the progression of neurologic symptoms was also reported. The diagnosis and cessation of the responsible agent are important in management.

A Rare Hernia Mimicking Implant in a Patient with Rectal Adenocarcinoma: Internal Herniation.

Internal herniation may be seen more frequently in patients with intra-abdominal surgery and malignancy history. We presented a 58-year-old male patient diagnosed with rectal adenocarcinoma seven years ago with a history of surgery and pelvic radiotherapy. When the abdominal computed tomography (CT) image was taken during routine oncology follow-up, a lesion mimicking a serosal implant on the anterior abdominal wall was detected. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging was performed the suspicion of recurrence. It was concluded that the lesion, which was evaluated as an implant in abdominal CT with 18F-FDG PET/CT imaging, was a spontaneously reducing internal herniation. 18F-FDG PET/CT imaging in cancer patients is crucial in illuminating the suspicion of recurrent lesions in these patients and sheds light on the course of the patients in oncology practice.

Vitiligo-like lesions associated with ribociclib in a woman with metastatic breast cancer.

INTRODUCTION: Cyclin-dependent kinase 4/6 inhibitors are new generation drugs that have recently been used in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negativenegative metastatic breast cancer. Recent studies have shown that the use of cyclin-dependent kinase 4/6 inhibitors significantly improves the outcomes of these patients. The most common side effects of cyclin-dependent kinase 4/6 inhibitors are hematological toxicity, gastrointestinal side effects, and fatigue. We aimed to present a case of metastatic breast cancer who was treated with ribociclib and developed vitiligo-like lesions after treatment. CASE REPORT: A 56-year-old female patient was diagnosed with locally advanced hormone receptor (+)/human epidermal growth factor receptor 2 (-) breast cancer in May 2000. She was followed up with hormonal therapy after adjuvant chemotherapy and radiotherapy. The patient progressed with lung metastases in 2012. Ribociclib, anastrozole, and leuprolide acetate were started in November 2021 after multiple-line chemotherapy. After six cycles of ribociclib, vitiligo-like lesions that developed in the last 1 month were detected on the upper extremities, both hands, neck, chest, and upper back. MANAGEMENT AND OUTCOME: The patient was referred to dermatology. Topical immunosuppressive therapy and oral corticosteroids were recommended. At the first and third-month follow-up examinations, vitiligo-like lesions were observed to persist. DISCUSSION: Vitiligo-like lesions are not a life-threatening side effect. However, it significantly affects the quality of life and disrupts the patient's compliance with treatment. Cyclin-dependent kinase  4/6 inhibitors can inhibit cell division or cause premature cell death by acting on the melanocyte cell cycle.

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.