Objective: CDK4/6 inhibitors constitute standard first-line therapy for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). We investigated real-world predictors of overall survival (OS), with particular focus on high ER expression (≥90%). Methods: In this multicenter, retrospective study, we analyzed 603 HR-positive/HER2-negative MBC patients treated with CDK4/6 inhibitors (ribociclib or palbociclib) between May 2020 and June 2024. We evaluated demographic, clinical, and pathological factors for their impact on OS using univariate and multivariate Cox regression analyses. Results: In univariate analysis, significantly longer OS was observed in endocrine therapy-naive patients (median OS: 51.0 vs. 33.3 months; p < 0.001), those without liver metastases (50.0 vs. 34.0 months; p = 0.019), bone-only metastases (57.7 vs. 40.5 months; p = 0.022), and PR-positive patients (50.0 vs. 36.0 months; p = 0.037). Patients with ER expression ≥90% showed a strong trend toward longer OS (49.0 vs. 41.0 months; p = 0.072). In multivariate analysis, endocrine therapy naivety (p = 0.045) and high ER expression (≥90%) (p = 0.031) emerged as independent predictors of superior OS. Conclusions: Our study identifies treatment naivety and exceptionally high ER expression (≥90%) as key independent predictors of prolonged OS in CDK4/6 inhibitor-treated MBC patients. These findings underscore the importance of early CDK4/6 inhibitor implementation and suggest that quantitative ER assessment may refine patient selection beyond conventional positivity thresholds.

Background: The Meet-URO score combines the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria with neutrophil-to-lymphocyte ratio (NLR) and bone metastasis status. Although developed in immune checkpoint inhibitor (ICI) cohorts, its performance among patients receiving first-line tyrosine kinase inhibitor (TKI) monotherapy is uncertain. Methods: We performed a multicenter, retrospective cohort study of 301 adults with histologically confirmed metastatic renal cell carcinoma (mRCC) treated with first-line TKI monotherapy (sunitinib, pazopanib, or cabozantinib) between 2008 and 2025 across five tertiary centers in Turkey. The primary endpoint was overall survival (OS). Meet-URO was calculated at treatment start and analyzed as prespecified risk strata (0–4, 5–8, 9). Kaplan–Meier estimates, Cox models, and Harrell’s C-index assessed discrimination, with bootstrapped 95% CIs. Results: Median follow-up was 40 months; median OS (mOS) was 25 months (95% CI, 21–29) and median progression-free survival was 10 months (95% CI, 8–12). Meet-URO stratified OS: 41 months for scores 0–4, 21 months for 5–8, and 7 months for 9 (log-rank p < 0.001). In multivariable analysis, Meet-URO remained independently prognostic (HR 1.73 for 5–8 vs. 0–4; HR 3.57 for 9 vs. 0–4; both p < 0.001). Discrimination was modest (C-index 0.722) and slightly lower than IMDC (C-index 0.745). NLR ≥ 3.2 was associated with inferior OS (19 vs. 37 months; p < 0.001). Bone metastasis was not significantly associated with OS (p = 0.27). Conclusions: Meet-URO is a valid prognostic tool for mRCC patients treated with first-line TKIs and identifies an ultra-high-risk subgroup (score = 9) with poor survival. While not superior to IMDC, Meet-URO may offer complementary risk information to support clinical monitoring and trial referral, particularly in settings where ICI combinations are restricted.

Objective: CDK4/6 inhibitors are the standard first-line treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, treatment response shows heterogeneity among patients. The objective of this multicentre, retrospective study is to investigate real-world parameters affecting overall survival (OS) in patients receiving CDK4/6 inhibitor therapy, particularly the effect of high oestrogen receptor (ER) expression (≥90%). Methods: A total of 603 HR-positive/HER2-negative MMK patients treated with a CDK4/6 inhibitor (ribociclib or palbociclib) from five centres were retrospectively reviewed. Age, menopausal status, metastatic status, metastatic sites, pathological subtype, HER2 status (low/negative), ER expression level (< 90% vs ≥90%), progesterone receptor (PR) status, and prior endocrine therapy (ET) or chemotherapy (CT) before CDK4/6 inhibitor were evaluated for their impact on OS using univariate and multivariate Cox regression analyses. Results: In the univariate analysis, OS was significantly longer in patients who did not receive ET prior to CDK4/6 inhibitor treatment (median OS: 51.0 months vs. 33.3 months; p< 0.01). OS was also better in patients without liver metastases (50.0 months vs. 34.0 months; p=0.019), those with bone metastases only (57.7 months vs. 40.5 months; p=0.022), and PR-positive patients (50.0 months vs. 36.0 months; p=0.037) also had better OS. OS was numerically longer in patients with ER expression ≥90% compared to those with < 90% (49.0 months vs. 41.0 months; p=0.072). In multivariate analysis, not having received ET prior to CDK4/6 inhibitor therapy (p=0.045) and high ER expression (≥90%) (p=0.031) were independently associated with better OS. Conclusion: Our study demonstrates that HR-positive/HER2-negative MBC patients who are naive to endocrine therapy prior to CDK4/6 inhibitor treatment and have high ER expression (≥90%) in their tumours derive greater OS benefit from this treatment. The ER expression level threshold of ≥90% may be proposed as a potential biomarker for predicting response to CDK4/6 inhibitor therapy. These findings necessitate further prospective studies to improve patient selection.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy represent the gold standard in the first-line treatment of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, the optimal timing of CDK4/6i initiation in patients with bone-only disease (BoD) remains a matter of clinical discussion. This multicenter retrospective study evaluated the impact of CDK4/6i treatment line (first-line vs. second-or-later-line) on progression-free survival (PFS) and overall survival (OS) in HR+/HER2− MBC patients with BoD. Methods: A total of 282 HR+/HER2− MBC patients with radiologically confirmed BoD treated across five tertiary academic centers were analyzed. All patients received bone-modifying agents (zoledronic acid or denosumab). Patients were categorized into Group 1 (first-line CDK4/6i, n = 193) and Group 2 (second-or-later-line CDK4/6i, n = 89). Baseline characteristics were recorded. Multivariable Cox proportional hazards models were adjusted for key clinicopathological variables. Results: The median PFS was 30.193 months in the first-line group and 19.253 months in the second/later-line group, with no statistically significant difference (p = 0.055). The median OS was 62.324 months in the first-line group and 72.00 months in the second/later-line group, which was significant in the univariate analysis (p = 0.036). However, this significance was not maintained in the multivariate analysis adjusting for potential confounders (p = 0.487). Except for strong ER positivity, baseline characteristics were balanced between groups. In the multivariate analysis, no clinical factor, including treatment line, independently and significantly impacted OS. Conclusions: In HR+/HER2− MBC patients with bone-only disease, first-line CDK4/6 inhibitor therapy demonstrates a trend toward superior PFS. After correcting for key observational biases, the later line of therapy does not independently alter OS. These findings reinforce that first-line CDK4/6 inhibitor plus endocrine therapy remains the definitive standard of care, and later-line initiation should be reserved solely for select clinical scenarios where first-line use was not feasible.

This multicentre real-world study evaluated the efficacy of targeted therapies in Turkish patients with metastatic squamous cell lung carcinoma harbouring driver mutations. Sixty-four patients with alterations such as EGFR, ALK, and ROS1 who received targeted agents were retrospectively analysed. EGFR mutations were most common (67.2%). Among EGFR-TKI-treated patients, median progression-free survival (PFS) and overall survival (OS) were 12.4 and 14.3 months, respectively. Alectinib yielded a median PFS of 18.6 months and OS of 29.8 months in ALK-positive patients, while crizotinib produced a median PFS and OS of 7 months in ROS1-positive patients. The overall response rate was 50% and the disease control rate 84.4%. Although targeted therapies prolonged PFS compared with chemotherapy, this improvement did not translate into a significant OS advantage, likely influenced by retrospective design and treatment crossover. Findings represent real-world outcomes in a molecularly defined subgroup.

Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC) is a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains incompletely characterized. We evaluated real-world outcomes and prognostic factors in a multicenter retrospective Turkish cohort treated with a CDK4/6 inhibitor plus endocrine therapy (June 2020–September 2025). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox methods. Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and the clinical benefit rate was 82.6%. Median PFS was 17.0 months and OS 47.0 months. PFS was numerically longer in BRCA1 than in BRCA2 carriers (25.0 vs. 14.0 months), although the difference was not statistically significant in the pairwise comparison (HR 1.50, 95% CI 0.88–2.56; log-rank p = 0.135); the dual BRCA1/2 subgroup (n = 3) had the poorest outcomes and was assessed descriptively. OS did not differ significantly between BRCA1 and BRCA2 carriers (57.0 vs. 49.0 months; log-rank p = 0.520). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at borderline significance (p = 0.050), but this was not confirmed in Cox regression. In multivariable analysis, ECOG ≥ 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.