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.

The effect of parity, breastfeeding history, and duration on clinical and pathological characteristics of breast cancer patients.

Background/aim: The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer. Materials and methods: A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child. Results: The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed. Conclusion: Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.

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.

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.

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.

Multidrug refractory aggressive metastatic TFE3 (+) renal cell carcinoma: A case report.

BACKGROUND: Transcription factor E3 (TFE3) related renal cell carcinomas constitute a very small percent of all renal tumors in adults. Prognosis mainly depends on the stage of the disease at the time of diagnosis which is often poor. There is yet to be a standardized treatment protocol. Treatment options include agents identical to TFE3(-) cell renal carcinoma treatment. We present a case of a young woman with a rapidly progressing metastatic TFE3 (+) renal cell carcinoma. CASE REPORT: A 31 year old female presented with abdominal mass, distension, nausea. Initial tests and tumor markers found to be normal. Abdominal CT scan revealed a left retroperitoneal mass along with three other neighboring masses in liver manifesting as metastases. Trucut biopsy and immunohistochemical staining confirmed the retroperitoneal mass as TFE3 (+) renal cell carcinoma.Management and outcome: Sunitinib, pazopanib, nivolumab, axitinib treatments are consecutively given after surgery. It is noteworthy that rapid progression was observed under nivolumab treatment. DISCUSSION: During surveillance, rapid progression is noted under consecutive immunotherapy which was unexpected. Thus, there is a need for more standardized treatment protocols and invention of new agents for management of TFE3 (+) renal cell carcinoma.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

A practical 16-day desensitization protocol in lenalidomide-induced non-immediate hypersensitivity reactions.

BACKGROUND: Desensitization in immediate-type hypersensitivity reactions (HRs) caused by chemotherapeutics is well described and standardized for many drugs. However, there are no standardized protocols in non-immediate HRs. OBJECTIVE: To evaluate the effectiveness of a 16-day desensitization protocol in the non-immediate HRs induced by lenalidomide. METHODS: According to our previously published slow desensitization protocol, we desensitized patients who had experienced non-immediate HRs attributable to lenalidomide. The protocol was started with the 1/100 of the daily-prescribed dose in milligrams of the culprit drug; then the doses were slowly increased to complete the procedure in 16 days. Demographic and clinical features of the patients were further appraised. RESULTS: Ten patients (mean age was 64.7 ± 10.8 years; 7 male) were successfully desensitized to lenalidomide. The mean reaction time was 7.3 ± 3.9 days in the history, and the reaction types were delayed urticaria (n = 4), eczematous rash (n = 3), and maculopapular eruptions (n = 3). The desensitization was successfully completed in 16 days in 9 patients. In 1 patient, maculopapular eruptions developed on the 11th day, and the patient was treated with corticosteroids. We repeated the previous tolerated dose longer and completed with a slower dose increasement, and the targeted dose was achieved in 35 days. CONCLUSION: The 16-day desensitization protocol seemed to be safe and effective in the non-immediate type drug HRs caused by lenalidomide.

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.

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.

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.

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.

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.

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.

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.