Background/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in the hormone receptor-positive/HER2-negative (mHRPBC) subtype. While clinical trials have demonstrated its efficacy, real-world data—especially those involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate real-world observational data describing the clinical outcomes, safety, and prognostic factors associated with SG treatment in patients with mTNBC or mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) plus hormone therapy. The clinical outcomes—including the progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0). Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. A high Eastern Cooperative Oncology Group Performance Status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG’s efficacy. SG was generally well tolerated; the most common AEs were alopecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG was associated with similar clinical outcomes and tolerability in both the mTNBC and mHRPBC subtypes. Although the real-world PFS and OS outcomes mirror those seen in clinical trials, the absence of a control group means that these findings should be interpreted descriptively rather than as confirmation of treatment efficacy. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.

Background/Objectives: Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in hormone receptor-positive/HER2-negative (mHRPBC) subtypes. While clinical trials have demonstrated its efficacy, real-world da-ta—especially involving both molecular subtypes—remain scarce. This multicenter, retrospective study aimed to evaluate the real-life effectiveness, safety, and prognostic factors associated with SG treatment in patients with both mTNBC and mHRPBC. Methods: A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to hormone therapy. Clinical out-comes—including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)—were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to NCI-CTCAE v5.0. Results: The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. Eastern cooperative oncology group performance status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG efficacy. SG was generally well tolerated; the most common AEs were alo-pecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). Conclusions: SG demonstrated comparable effectiveness and a managea-ble safety profile in real-world patients with both mTNBC and mHRPBC. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.

Background and Objectives: This study aimed to compare the real-world outcomes of first-line pembrolizumab monotherapy (Mono-IO) versus pembrolizumab plus platinum-based chemotherapy (IO + ChT) in patients with metastatic non-small cell lung cancer (mNSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. Materials and Methods: This retrospective, multicenter, real-world study evaluated 148 patients with mNSCLC and PD-L1 expression ≥ 50% who received either first-line Mono-IO or IO + ChT. Overall survival (OS), progression-free survival (PFS), and clinical benefit rate were compared between the two treatment strategies. Additionally, clinical prognostic factors, patterns of progression, and post-progression treatments were analyzed. Survival outcomes were assessed using Kaplan–Meier estimates, multivariable Cox regression, and restricted mean survival time (RMST) analysis. Results: Patients in the Mono-IO group were significantly older (median 69 vs. 63 years; p < 0.001) and had a higher proportion of ECOG PS 2 (35.3% vs. 5.2%; p < 0.001). No significant differences were observed between Mono-IO and IO + ChT in median OS (32.0 vs. 26.0 months; p = 0.559) or PFS (19.6 vs. 19.4 months; p = 0.572). In an exploratory multivariable analysis adjusting for organ-specific metastases and antibiotic exposure, ECOG PS ≥ 1 (aHR: 1.86, 95% CI: 1.16–2.97; p = 0.009), antibiotic use (aHR: 1.85, 95% CI: 1.16–2.95; p = 0.010), and liver metastasis (aHR: 2.58, 95% CI: 1.16–5.74; p = 0.020) were independent predictors of worse OS. Conversely, PD-L1 TPS ≥ 90% (aHR: 0.56, 95% CI: 0.35–0.91; p = 0.018) was independently associated with superior OS. In exploratory subgroup analysis, a numerical survival trend favoring Mono-IO was observed in patients with PD-L1 TPS ≥ 90%, although this finding remains hypothesis-generating. Following disease progression, 64.7% of patients received no further systemic therapy. Conclusions: In this real-world cohort, no statistically significant differences in OS or PFS were detected between Mono-IO and IO + ChT; however, the wide confidence intervals do not exclude clinically meaningful differences, and equivalence cannot be inferred from these data. PD-L1 TPS ≥ 90% may potentially serve as a biomarker to identify patients who derive benefit from monotherapy, although this exploratory finding requires validation in larger cohorts. Given that the majority of patients did not transition to subsequent therapy in routine practice, likely reflecting multifactorial host frailty and rapid disease evolution, first-line therapeutic optimization warrants careful individualized consideration.

Background: Non–small cell lung cancer (NSCLC) is one of the most commonly diagnosed malignancies and a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors such as nivolumab have become a standard option in the second-line and later-line settings, identifying patients who derive meaningful benefit remains challenging. Established biomarkers, including PD-L1 expression, have shown limited predictive performance. The Lung Immune Prognostic Index (LIPI), a simple score reflecting systemic inflammation and tumor burden, has emerged as a potential prognostic tool. However, its real-world prognostic value in patients receiving nivolumab after first-line therapy remains insufficiently defined. Methods: This retrospective, single-center study included 109 patients with advanced NSCLC who received nivolumab following disease progression after first-line therapy. LIPI was calculated based on derived neutrophil-to-lymphocyte ratio (dNLR ≥3) and lactate dehydrogenase (LDH) levels above the upper limit of normal. Patients were stratified into three groups (LIPI 0-1-2). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and compared with the log-rank test. Multivariable Cox proportional hazards models were used to identify independent prognostic factors. Results: Patients were categorized as LIPI 0 (n=32), LIPI 1 (n=45), and LIPI 2 (n=32). A clear stepwise deterioration in outcomes was observed across increasing LIPI categories. Median PFS was not reached in the LIPI 0 group, and was 340 days and 109 days in the LIPI 1 and LIPI 2 groups, respectively (p < 0.001). Similarly, median OS was not reached in the LIPI 0 group, while it was 820 days and 201 days in the LIPI 1 and LIPI 2 groups, respectively (p < 0.001). In multivariable analysis, LIPI remained independently associated with both PFS and OS. In contrast, PD-L1 expression and other clinicopathological variables were not independently associated with survival outcomes, suggesting that the prognostic impact of LIPI is independent of PD-L1. Conclusions: LIPI appears to be a robust, readily available prognostic marker in patients with advanced NSCLC treated with nivolumab beyond the first-line setting. Its independent association with survival outcomes, irrespective of PD-L1 expression, suggests that it captures distinct biological processes related to systemic inflammation. Incorporation of LIPI into routine clinical practice may improve risk stratification and support more individualized treatment decisions. Notably, LIPI may provide complementary prognostic information beyond tumor-specific biomarkers such as PD-L1.

Background: The Lung Immune Prognostic Index (LIPI), based on the derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase, may reflect systemic inflammation and tumor-related metabolic burden. This study evaluated the prognostic value of pretreatment LIPI and its relationship with programmed death-ligand 1 (PD-L1) expression in patients with advanced non-small cell lung cancer (NSCLC) receiving nivolumab after first-line therapy. Methods: A total of 158 patients were included in this retrospective, single-center study. Patients were classified into LIPI 0, LIPI 1, or LIPI 2 groups according to their pretreatment LIPI scores. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis and multivariable Cox regression. The prognostic value of LIPI was also evaluated within PD-L1-negative and PD-L1-positive subgroups, and LIPI × PD-L1 interactions were explored. Harrell’s concordance index was used to examine whether adding LIPI improved model discrimination beyond clinical variables and PD-L1 expression. PD-L1 data were available for 145 patients. Results: Median PFS was 566, 340, and 109 days for the LIPI 0, LIPI 1, and LIPI 2 groups, respectively, while median OS was 841, 760, and 201 days, respectively; the differences were statistically significant for both outcomes (both p < 0.001). The objective response rate (ORR) was 55.6%, 36.5%, and 4.9%, whereas the disease control rate (DCR) was 75.9%, 65.1%, and 14.6% in the LIPI 0, LIPI 1, and LIPI 2 groups, respectively (both p < 0.001). In multivariable analyses, higher LIPI remained independently associated with shorter PFS and OS, with the strongest association observed in the LIPI 2 group. LIPI also differentiated survival outcomes within both PD-L1-negative and PD-L1-positive subgroups, although no significant LIPI × PD-L1 interaction was identified for PFS or OS. The addition of LIPI increased the C-index from 0.583 to 0.698 for PFS (ΔC-index, 0.115; p < 0.001) and from 0.588 to 0.697 for OS (ΔC-index, 0.109; p = 0.003). Conclusions: Pretreatment LIPI was independently associated with PFS and OS in patients with advanced NSCLC receiving nivolumab after first-line therapy. Its association remained after adjustment for available PD-L1 expression data, and its addition improved model discrimination. These findings suggest that LIPI may provide prognostic information complementary to PD-L1 expression and routinely available clinical factors.