Does the Timing of Cytoreductive Nephrectomy Impact Outcomes? Analysis of REMARCC Registry Data for Patients Receiving Tyrosine Kinase Inhibitor Versus Immune Checkpoint Inhibitor Therapy.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy. Conclusions and clinical implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC. Patient summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.

Comparison of efficacy and safety of 5-FU or capecitabine combined with cisplatin and docetaxel (mDCF and mDCX) as a first-line chemotherapy regimen in her 2-negative metastatic gastric cancer patients: A retrospective study.

The prognosis of metastatic gastric cancer (GC) is poor, with a median survival time of less than a year. Capecitabine is a prodrug, metabolized by thymidine phosphorylase to its cytotoxic metabolite (5-FU). Few studies have compared capecitabine and 5-FU in mGC. In this retrospective study, we compared the efficacy and safety of modified DCF (mDCF) (docetaxel, cisplatin, and 5-FU) and modified DCX (mDCX) (docetaxel, cisplatin, and capecitabine) regimens for first-line treatment in patients with mGC. The study included 112 mGC patients treated with either mDCF (n = 69) or mDCX (n = 43) between 2010 and 2021. Demographic data, response rate, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. The complete response rate in the mDCF group was 10.1%, whereas the complete response rate in the mDCX group was 2.3%. The partial response rate for mDCF and mDCX were 29% and 37%, respectively. The 2 treatment arms of the study had the same objective rate of response and disease control rate (DCR). PFS and OS rates were comparable between the 2 groups. The median PFS in the mDCF and mDCX arms were 6.0 months (95% CI, 4.87-7.14) and 5.0 months (95% CI, 4.10-5.90) respectively (P = .08). The median OS in the mDCF and mDCX arms were 9.0 months (95% CI, 7.53-10.47) and 9.0 months (95% CI, 6.87-11.11) respectively (P = .07). Neutropenia, asthenia, stomatitis, and nausea/vomiting were the most frequently reported grade 3 to 4 adverse events (AEs). The rates of grade 3/4 AEs and dose reduction were comparable between the 2 groups. There was no treatment discontinuation due to grade 3 to 4 AE. As a first-line treatment for patients with mGC, mDCX and mDCF regimens have comparable efficacy and tolerability profiles.

Single-agent temozolomide as salvage therapy in heavily pretreated metastatic sarcoma patients.

BACKGROUND: Treatment options for patients with metastatic sarcoma are limited. The goal of this study was to investigate the effectiveness of temozolomide in pretreated patients with soft tissue sarcoma. METHODS: We recorded the pathological, clinical, and treatment data of the patients with metastatic soft tissue sarcoma retrospectively. We evaluated the efficacy and side effects of temozolomide in this patient group. RESULTS: This study involved 16 patients. The average age was detected as 48 (21-73) years. Six (37.5%) patients had de-novo metastatic disease at diagnosis. Primary of tumors had originated from intra-abdominal (43.7%), extremity (31.3%), head-and-neck (12.5%), and intrathoracic (12.5%) regions. The patients previously had received at least two different chemotherapy regimens (75%), pazopanib (50%) and palliative radiotherapy (31.3%). Temozolomide-related median progression-free survival time was found as 3.5 (95% CI, 2.6-4.3) months. One patient (6.3%) had a partial response, while four patients (25%) had stable disease. Nine individuals (56.3%) had grade 1-2 adverse events, while one patient (6.3%) had grade 3-4 adverse events. CONCLUSIONS: We observed that temozolomide was well tolerated but had limited efficacy in the treatment of metastatic sarcoma patients. In patients with extensively pretreated soft tissue sarcoma, temozolomide may be considered a therapeutic option as a single-agent.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Therapeutic efficacy of high-dose chemotherapy with autologous stem-cell transplantation in 44 relapsed or refractory germ-cell tumor patients: A retrospective cohort study.

Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.

Disease characteristics and prognostic factors of colorectal cancer patients with bone metastasis: A real-world data from Turkey.

BACKGROUND: Bone metastasis is rarely seen in colorectal cancer (CRC) patients, and there is insufficient data available regarding such cases. The study aimed to identify the prognostic factors and characteristics associated with overall survival in patients with bone metastatic CRC. METHOD: Data from bone metastatic CRC patients referred to a high-volume tertiary cancer center in Turkey, between January 2018 and April 2021, were retrospectively collected. The records of 150 consecutive patients treated for bone metastases due to CRC were reviewed. Overall survival curves were generated by the Kaplan-Meier method and analyzed using the log-rank test. RESULTS: Median age was 55 years (19-86 years). Bone metastases were more common in men and those with metachronous metastases. The axial skeleton was the most commonly involved site, and patients were frequently presented with single bone metastasis. Peritoneal metastases were significantly correlated with extra-axial metastases (P = 0.002), and radiotherapy was applied to axial metastases significantly, more frequently (P = 0.02). Lung metastasis was also more prevalent in K-RAS mutated patients (P = 0.008). The median survival time from diagnosis of bone metastasis was 8.3 months (95% confidence interval (CI), 5.5-10.6), and the three-year survival rate was 76.9% (95% CI, 69.8-84.0). Multivariate analysis revealed that brain metastases, right-sided colon tumor, high serum ALP, and Ca 19-9 levels were independent poor prognostic factors (P = 0.01, 0.02, <0.001, and 0.04, respectively). CONCLUSIONS: The location of CRC correlates significantly with the site of bone metastasis; the prognosis of CRC patients with bone metastasis is very poor, and the significant poor prognostic factors are brain metastases, right-sidedness, high serum ALP, and Ca 19-9 levels. More attention should be paid to bone metastasis in CRC patients.

Is there any diagnostic value of serum caveolin-1 levels on the determination of pancreatic adenocarcinoma?

BACKGROUND: Caveolin-1 (CAV-1) is a vital component in cancer pathogenesis, as its expression determines the survival of patients with cancer. This study investigates CAV-1 serum levels in pancreatic adenocarcinoma (PA) patients and their role in tumor progression and prognostic factors. METHOD: The trial included 33 patients with pathologically confirmed pancreatic cancer (PC). The enzyme-linked immunosorbent assay (ELISA) method was used to measure the concentrations of CAV-1 in the blood. The study also included 20 healthy subjects. The statistical analysis was two-sided, and a P value of ≤ 0.05 was determined as statistically significant. RESULTS: The median age of the subjects was 59 years (32-84 years) at the time of diagnosis. There were 13 (39%) female participants. In 21 (63%) patients, the primary focus was the pancreatic head. In 23 stage IV patients, hepatic metastasis (n = 19, 83%) was observed. Only one patient (3%) was still alive at the end of the study period. Palliative chemotherapy (CTx) was provided, with 39% of the 23 patients responding to it. The overall survival (OS) rate in this cohort was 41.3 ± 8.3 weeks at a 95% confidence interval (CI), after 25-58 weeks. Serum baseline CAV-1 values among patients with PA were significantly higher compared with controls (p = 0.009). Patients with poor performance status, a pancreatic head tumor, lower albumin levels, higher serum carcinoembryonic antigen (CEA) levels, and higher CA 19.9 levels had significantly higher serum CAV-1 levels (p = 0.01, P = 0.05, P = 0.03, P = 0.02, and P = 0.04, respectively). However, CAV-1 did not show any prognostic value (p = 0.75). CONCLUSION: Although serum CAV-1 is a useful diagnostic marker in PC patients, it is not a prognostic or predictive marker.

Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Comparison of second-line treatments in metastatic renal cell carcinoma patients: A single-center experience.

Renal cell carcinoma is the 10th most common type of cancer, accounting for 3.7% of all cancers. Our study examines patients with metastatic renal cell carcinoma who received Axitinib or Nivolumab as second-line treatment. This study was designed as a retrospective analysis. Patients who received Axitinib or Nivolumab as second-line treatment for metastatic renal cell carcinoma at the Istanbul University Oncology Institute Medical Oncology outpatient clinic were included in the study. A total of 81 patients were included in the study, with a median follow-up period of 18.5 months (2-260 months). Of these patients, 29 (35.8%) received Axitinib as second-line treatment, while 52 (64.2%) received Nivolumab. The median duration of second-line treatment was 14 months (6-52) for Axitinib and 13.5 months (3-77) for Nivolumab. In our study, Nivolumab was found to have statistically better PFS and OS outcomes than Axitinib in male patients, patients diagnosed with metastatic disease, those with a favorable or intermediate International Metastatic Renal Cell Carcinoma Database Consortium risk score, patients diagnosed with metastatic disease or who developed metastasis within 12 months of diagnosis, those who developed metastasis ≥ 24 months after diagnosis, and patients with metastasis in a single organ. Both drugs are recommended as monotherapy for second-line and later treatments in the current NCCN guidelines for kidney cancers. Although there is no study in the literature showing that axitinib is more effective than nivolumab, nivolumab was found to be much more effective than axitinib in our study. Prospective studies with higher number of patients are needed on this subject.

Efficacy and outcomes of systemic chemotherapy in posttransplant and immunosuppression associated Kaposi sarcoma: Twenty years experience of a tertiary cancer center.

Kaposi sarcoma is a malignant angioproliferative disease, and human herpesvirus-8 plays a major role in its etiology. Iatrogenic Kaposi sarcoma (IKS) can occur in patients undergoing immunosuppressive therapy. The treatment strategy for patients with IKS is immunosuppressive therapy modification. However, it is unclear which chemotherapy drug is the most effective and safe in the treatment of IKS. Therefore, we investigated the efficacy and safety of systemic treatment in patients with IKS at our tertiary cancer center. This cross-sectional retrospective study analyzed the clinical data of 22 patients diagnosed with IKS between January 2000 and January 2020. The patients were divided into the following 2 groups according to the transplantation status: organ transplant recipient (OTR) group and non-organ transplant recipient (non-OTR) group. Of the 22 patients, 12 were included in the OTR group and 10 were included in the non-OTR group. The median patient age at diagnosis was 52.1 years in the OTR group and 68.1 years in the non-OTR group. The median overall survival (OS) was 65.4 months in the OTR group, while the median OS was not reached in the non-OTR group. There was no statistically significant difference in OS between the 2 groups (P = .45). The 5-year OS rate among all patients was 54%. In the OTR group, the objective response rate and disease control rate were 50% and 83%, respectively, and in the non-OTR group, the objective response rate and disease control rate were 60% and 90%, respectively. Chemotherapy was well tolerated in both groups. Hematological toxicities were the main dose-limiting adverse events. Grade III/IV leucopenia and neutropenia were observed in 5 and 4 patients, respectively; however, no patient experienced febrile neutropenia. No chemotherapy-related death occurred. Systemic chemotherapy is an effective treatment and can be considered for disease control in patients with an aggressive disease course, who do not experience regression with immunosuppressive therapy modification.

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

BACKGROUND: We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. METHOD: Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. RESULTS: A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65 years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45 cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. CONCLUSIONS: Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression.

The purpose of the study was to assess the prognosis of HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression and investigate the predictors of complete response. HER2-positive metastatic breast cancer patients who received long-term trastuzumab were included in the study. Predictors of complete response were analyzed with binary regression analysis. The prognosis of patients who had their trastuzumab-based treatment terminated was assessed. Eighty patients were involved in the study. The patients were received with trastuzumab for a median of 62 months (12-191). A complete response was observed in 60 (75%) patients. The median duration to development of complete response was found as 14.8 months (2.4-55). In logistic regression analysis: using endocrine therapy with trastuzumab (p = 0.04), menopausal status (p = 0.03), and the number of metastatic sites (p = 0.01) were found to be statistically significant factors for a complete response. Trastuzumab-based therapy of fifteen patients was terminated, six (40%) patients continued to receive an aromatase inhibitor, and nine (60%) patients were followed up without treatment. After termination of trastuzumab, at a median follow-up of 32 months (11-66), recurrence was detected in two (13.3%) patients. We detected that menopausal status, the number of metastatic sites, and using endocrine therapy with trastuzumab were predictors of complete response in HER2-positive metastatic breast cancer patients who received long-term trastuzumab-based therapy. We observed that HER2-positive metastatic breast cancer patients may be completely cured with trastuzumab-based therapy. There are no defined criteria for termination of trastuzumab treatment in this selected patient group. It is necessary to confirm our data with multicenter studies involving a large number of patients.

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.

Fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) regimen in the first-line treatment of metastatic gastric cancer: A single-center experience.

Objective: The median survival time for metastatic gastric cancer that has a poor prognosis is usually shorter than 1 year. The fluorouracil, oxaliplatin, and docetaxel (FLOT) regimen is observed to be effective in the neo-adjuvant treatment of gastric cancer. However, data on the FLOT regimen in metastatic gastric cancer are limited. The current study aims to evaluate the safety and efficacy of the FLOT regimen in metastatic gastric cancer in real life. Study Design: Retrospective study. Place and Duration of Study: The study was performed in an Institute of Oncology of a university and included the patients diagnosed between January 2015 and December 2020. Methodology: In addition to the clinicopathological data of patients with human epidermal growth factor receptor 2 (HER-2)-negative metastatic gastric cancer, we retrospectively evaluated the survival and treatment-related toxicities. The FLOT regimen (Fluorouracil 2600 mg/m2 24 hours continuous intravenous infusion, leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2 on day 1) every 2 weeks was used in all patients. Results: The study included 94 patients who were followed up for a median of 11.1 (min-max: 1.5-65.8) months. The number of male patients was 60 (63.4%), and the median age was 58 (min-max: 27-78) years. The primary tumor was located in the stomach (72.3%) and gastroesophageal junction (27.7%). The objective response rate was observed in 64.8% of the patients. The median overall survival was 13.5 (95% CI: 9.2-17.8) months, whereas the progression-free survival was 7 (95% CI: 5.7-8.3) months. The 1-year survival rate was 53.6%. Complete response was detected in 7.4% of the patients. Among grade 3-4 toxicities, neutropenia (44.6%), leukopenia (27.6%), neuropathy (12.7%), and fatigue (9.5%) were the most common observed toxicities. Conclusion: FLOT is a highly active option in the first-line treatment of metastatic gastric cancer, with a favorable safety profile.

Prognostic Factors Influencing Progression-Free Survival in HER2-Positive Metastatic Breast Cancer Patients Who Were Treated With A Combination of Lapatinib and Capecitabine.

Objective: The aim was to assess the prognostic variables in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients receiving lapatinib plus capecitabine. Materials and Methods: Retrospective data on HER2-positive metastatic breast cancer patients who received lapatinib and capecitabine were analyzed. Survival outcome was obtained with Cox regression analysis and the Kaplan-Meier method. Results: The study included 102 patients. Forty-four (43.1%) patients had de novo metastatic disease. The most frequent metastatic sites were, in order, bone (61.8%), brain (57.8%), liver (35.3%), and lung (34.3%). All of the patients had previously received chemotherapy based on trastuzumab. With combined lapatinib and capecitabine, complete response was observed in 7.8%, partial response in 30.4%, and stable disease in 24.5%. Progression-free survival was 8 (95% confidence interval, 5.1-10.8) months. In multivariable analysis, endocrine therapy (p = 0.02), de novo metastatic disease (p = 0.02), and age (p = 0.02) were prognostic factors for progression-free survival. However, the number of chemotherapy cycles with trastuzumab, palliative radiotherapy, history of breast surgery, and the number of metastatic sites were not significant in this respect. Conclusion: These results have demonstrated the effectiveness of lapatinib plus capecitabine in metastatic HER2-positive breast cancer patients. Furthermore, unfavorable prognostic factors for progression-free survival were shown to be hormone-negative tumor, de novo metastatic disease, and young age.

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.

Weekly paclitaxel treatment in the first-line therapy of classic Kaposi sarcoma: A real-life study.

Kaposi sarcoma is an angioproliferative disease associated with human herpes virus 8 infection. Classic Kaposi sarcoma (CKS) usually develops in older age. Although CKS often does not require systemic therapy, systemic therapy can be administered in progressively symptomatic patients. In this real-life study, we purposed to determine effectiveness and safety of weekly paclitaxel therapy in the first-line treatment of CKS. In this cross-sectional retrospective study, we analyzed the clinical data of 44 patients with CKS who received first-line paclitaxel therapy between January 2000 and December 2020. Paclitaxel was administered by intravenous infusion 80 to 100 mg/weekly. The median age of the patients was 67 years (range, 39-86 years), and majority male (77.2%). All patients had cutaneous involvement in extremities. The median follow-up time from paclitaxel treatment was 39.1 (range, 3.7-173.5) months. The median progression free survival from start of therapy was 35.1 months (range, 2-144 months). Complete response, partial response and stable disease were observed in 7 (15.9%), 28 (63.7%) and 6 (13.6) patients, respectively. Objective control rate was 79.6%, and the median response time after the last dose of paclitaxel was 18.2 months. A total of 4 patients (9.1%) had grade 3 to 4 neutropenia, but it was not complicated by febrile neutropenia. Three patients (6.8%) experienced grade 3 to 4 peripheral neuropathy. No patient had grade 3 to 4 allergic reaction. There was no drug-related death. According to our results, paclitaxel is an effective therapy option with an acceptable safety profile for patients with advanced CKS.

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.