Shembesh, Rana H.

e13167 Background: Abemaciclib represents a significant therapeutic advancement in the treatment of advanced metastatic breast cancer. As a selective protein-dependant kinase 4 and 6 (CDK4/6) inhibitor, it acts as a growth blocker. This study aims to evaluate the efficacy and safety of abemaciclib in combination with endocrine therapy for patients with metastatic breast cancer. Methods: We conducted an electronic search on December 27, 2024 using PubMed, Scopus, and the Cochrane database. Our inclusion criteria involved only randomized clinical trials evaluating the efficacy and safety of abemaciclib in combination to endocrine therapy in advanced breast cancer. Our primary outcomes were progression-free survival, overall response rate, overall survival, and grade 3 or 4 adverse effects. The hazard, odds, and risk ratios with 95% confidence intervals were used to determine the effect size. A random-effects model was applied. Results: Out of the 1,648 articles screened, only seven papers from five clinical trials met our inclusion criteria, comprising a total of 2,362 patients. Progression-free survival was significantly improved with abemaciclib in combination with endocrine therapy compared to endocrine therapy alone (hazard ratio: 0.58; 95% CI: 0.51–0.65; p < 0.001). Moreover, abemaciclib improved overall survival (hazard ratio: 0.78; 95% CI: 0.66–0.91; p = 0.002). Additionally, the overall response rate was higher with abemaciclib plus endocrine therapy compared to endocrine therapy alone (odds ratio: 2.75; 95% CI: 1.98–3.80; p < 0.001). However, grade three or higher adverse events were significantly more common in the abemaciclib group (risk ratio: 2.62; 95% CI: 2.30–2.99; p < 0.001). Conclusions: Abemaciclib combined with endocrine therapy is an effective treatment option for patients with HR-positive, HER2- negative advanced breast cancer. This combination significantly improves progression-free survival, overall survival, and response rate, making it a valuable therapeutic option in breast cancer. However, higher adverse events were observed in the abemaciclib group.

e16052 Background: Patients with esophageal squamous cell carcinoma (ESCC) who fail definitive treatment are candidates for second-line therapy. They often present with more aggressive disease and suboptimal responses to definitive treatments. In this individual patient-level meta-analysis, we aim to evaluate the efficacy of PD-1/PD-L1 inhibitors as second-line treatment in advanced ESCC. Methods: A systematic search of PubMed, Scopus, and Cochrane databases (December 5, 2024) identified randomized controlled trials (RCTs) comparing PD-1/PD-L1 inhibitors to chemotherapy as second-line treatment for advanced ESCC. Kaplan-Meier (KM) curves were reconstructed, and individual patient data (IPD) were extracted using R scripts. A patient-level meta-analysis was performed using the reconstructed IPDs and the Cox proportional hazards regression model. The Schoenfeld residuals test and Restricted Mean Survival Time (RMST) were also applied. The following R packages were used: MASS, Splines, survival, survRM2, survminer, and dbplyr . Results: Out of 3,930 records, five RCTs met the criteria: four phase 3 trials and one phase 2 trial (ORIENT-2), all were open-label, comparing PD-1 inhibitors to chemotherapy. Overall survival (OS) improved significantly with PD-1/PD-L1 inhibitors compared to chemotherapy (HR: 0.718, 95% CI: 0.650–0.793, p < 0.001). For patients with CPS ≥ 10, OS further improved (HR: 0.626, 95% CI: 0.446–0.878, p = 0.007), ), indicating an additional beneft in those with high PD-1 expression. The proportional hazards assumption was met for both OS and CPS ≥ 10 (Schoenfeld residuals test: p > 0.05). Progression-free survival (PFS) showed no significant difference (HR: 0.913, CI: 0.828–1.007, p = 0.069). However, the proportional hazards assumption was violated (Schoenfeld residuals test p < 0.001); therefore, these results should be interpreted with caution. PFS was further evaluated using RMST at 6, 12, 18, and 24 months. At 6 months, no significant difference was observed (RMST difference: -0.047, p = 0.593). However, PD-1 inhibitors showed significant differences at 12 months (0.37 months, p = 0.022), 18 months (0.74 months, p = 0.001), and 24 months (0.97 months, p < 0.001). Despite these significant differences, the magnitude of the difference is relatively small and may not be clinically meaningful. Conclusions: PD-1/PD-L1 inhibitors as second-line therapy improve overall survival in patients with advanced esophageal squamous cell carcinoma, compared to chemotherapy. However, the improvements in progression-free survival (PFS) were modest, and the clinical significance of these PFS benefits may be limited.