Background: The current study aimed to evaluate the effect of the time duration to reach the lowest prostate-specific antigen (PSA) from the onset of first-line hormonal treatment (time to nadir PSA, TTNpsa) on survival in castration-naive metastatic prostate cancer (CN-MPC) patients. Methods: Eighty patients who had PSA response >80% with first-line hormonal therapy (luteinizing hormone-releasing hormone, LH-RH analog +/- bicalutamide) were included in this study. Results: Under androgen deprivation therapy (ADT), a significant positive correlation was found between TTNpsa, nadir PSA (Npsa) duration, and progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). There was no correlation between TTNpsa and Npsa duration. TTNpsa and Npsa durations were independently correlated with PFS and OS. In patients with TTNpsa value ≥19 weeks, the median PFS was 126 (95% CI, 68–184) weeks compared with TTNpsa <19-week group in which the median PFS was 44 (95% CI, 26–62) weeks (p = 0.033). In patients with TTNpsa value ≥19 weeks, the median OS was 242 (95% CI, 169–315) weeks compared with TTNpsa 1 ng/mL (41 weeks, 95% CI, 34–48) (p < 0.001). The median OS was significantly longer in the patient group with nadir PSA ≤1 ng/mL (296 weeks, 95% CI, 220–272) compared to the group with >1 ng/mL (131 weeks, 95% CI, 84–178) (p = 0.002). In patients with nadir PSA ≤1 ng/mL (n = 40), there was no relationship between TTNpsa and Npsa duration with both PFS and OS. However, in patients with nadir PSA >1 ng/mL (n = 40) subgroup, there was a significant positive correlation between TTNpsa and PFS, and OS (p < 0.001, P = 0.016, respectively). Conclusion: In CN-MPC who received first-line ADT, especially in the group with the nadir PSA value >1 ng/mL, the duration of TTNpsa was positively correlated with PFS and OS.

Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cord compression, or hypercalcemia. Bone-modifying agents (BMAs), such as denosumab and zoledronic acid, are crucial in reducing the frequency and severity of SREs. The inhibition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has emerged as the standard treatment for hormone receptor-positive metastatic breast cancer, demonstrating significant improvements in survival outcomes. This study aims to compare the effectiveness of denosumab and zoledronic acid in preventing SRE in patients receiving CDK4/6 inhibitors with endocrine therapy. Materials and Methods: This retrospective study included 328 patients diagnosed with bone metastatic breast cancer receiving first-line CDK4/6 inhibitor therapy (palbociclib or ribociclib). Patients were assigned to receive either subcutaneous denosumab or intravenous zoledronic acid every 4 weeks. Time to the first skeletal-related event post bone-modifying agent initiation, SRE incidence, and the safety data were evaluated. The data were analyzed using independent samples t-tests, chi-square tests, and Kaplan–Meier methods for time-to-event data. Results: In the denosumab group, the median time to the first skeletal-related event was significantly longer than in the zoledronic acid group (44.55 months and 29.16 months, respectively). Denosumab treatment was associated with a statistically significant reduction in the risk of developing the first SRE after bone-modifying agent initiation compared to zoledronic acid (HR: 0.56, p = 0.001). Additionally, ECOG PS and the number of metastatic bone sites were identified as independent prognostic factors for time to the first SRE. The safety profile was consistent with previous studies reported in the literature. Conclusions: Our study demonstrated that when used with CDK4/6 inhibitors, denosumab is associated with a delay in SREs and a lower SRE incidence than zoledronic acid in patients with bone metastases. These findings support the efficacy of denosumab in preventing SREs and suggest that CDK4/6 inhibitors may have distinct effects on the bone microenvironment, particularly when combined with denosumab.

Background/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort. Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late). Results: Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions (p < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions (p < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS. Conclusions: Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject.

Background/aim: The aim of our study was to compare the efficacy and the safety of the FLOT and the modified DCF (mDCF) regimens in patients with metastatic gastric (GC) and gastroesophageal junction (GEJ) adenocarcinoma as first-line treatment. Materials and methods: The medical records of 72 patients were retrospectively reviewed. Survivals and hematological adverse events of the patients were examined. Factors affecting survivals were analyzed in univariate analysis. A multivariate analysis was performed with the factors contributing to survivals in univariate analysis. Results: The median PFS (mPFS) was 10.1 months (95% CI, 6.8?13.4) in the FLOT arm (n = 33) and 7.4 months (95% CI, 9.1?21.6) in the mDCF arm (n = 39) (p = 0.041). The median OS (mOS) was 12.9 months (95% CI, 9.7?16.1) in the FLOT arm and 15.4 months (95% CI, 9.1?21.6) in the mDCF arm (p = 0.622). It was found that all grade neutropenia was 51.3% vs. 72.7% (p = 0.063), febrile neutropenia was 8.3% vs. 6.3% (p = 0.743), and thrombocytopenia was 48.7% vs. 51.5% (p = 0.813) in the FLOT and mDCF arms, respectively. Anemia was 59% in the FLOT arm and 100% in the mDCF arm (p < 0.001). Grade 3-4 anemia was 7.7% in the FLOT arm and 24.2% in the mDCF arm (p = 0.052). Conclusion: It was shown that the mPFS was significantly increased in the FLOT arm compared to the mDCF arm as the first-line treatment in patients with metastatic GC and GEJC. Hematological adverse events were more favorable in the FLOT arm than in the mDCF arm.

Introduction Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have emerged as promising treatments for advanced NSCLC patients without actionable mutations. However, predicting treatment response remains challenging, especially in second-line settings. Although PD-L1 is the only validated biomarker, additional prognostic tools are needed. Systemic inflammation markers such as the neutrophil-to-lymphocyte ratio (NLR) show potential but remain underused. Myeloid-derived suppressor cells (MDSCs), linked to immunotherapy resistance, are associated with increased splenic volume. Therefore this study introduces a splenic index score, combining pre-immunotherapy splenic volume and NLR, to evaluate its prognostic value in NSCLC patients treated with nivolumab in the second-line setting. We analyzed 50 patients with metastatic non-small cell lung cancer (NSCLC) who received nivolumab as second-line or later therapy. Baseline splenic volume and neutrophil-to-lymphocyte ratio (NLR) were assessed using imaging and laboratory data prior to nivolumab initiation. The Splenic Index Score for each patient was calculated using the formula: (baseline splenic volume) × (NLR). Additionally, we evaluated the impact of other factors, including body mass index (BMI), tumor PD-L1 expression, Eastern Cooperative Oncology Group (ECOG) performance status, and sites of metastasis. The median Splenic Index score was 877.3 (range: 180–4830). A higher Splenic Index score was significantly associated with worse overall survival (OS) and progression-free survival (PFS) (p = 0.001 and p = 0.03, respectively). Specifically, patients with a high Splenic Index score had a median PFS of 3 months, compared to 8 months in those with a low Splenic Index score (HR 1.96, 95% CI 1-3.7, p = 0.03). Similarly, the median OS was 4 months for patients with a high Splenic Index score, while it was 15 months for those with a low score (HR 3.5, 95% CI 1.6–7.3, p = 0.001). Baseline splenic volume, basal NLR, and tumor PD-L1 expression were also evaluated; however, no significant differences in PFS or OS were observed for these parameters. Our study demonstrates that the splenic index score, derived from combining radiological and peripheral inflammatory biomarkers, serves as a predictive tool for progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients receiving second-line nivolumab therapy.