Benefit of second-line therapy for advanced esophageal squamous cell carcinoma: a tri-center propensity score analysis

BACKGROUND: The level of evidence for palliative second-line therapy in advanced esophageal squamous cell carcinoma (aESCC) is limited. This is the first study that reports efficacy data comparing second-line therapy + active symptom control (ASC) versus ASC alone in aESCC. METHODS: We conducted a tri-center retrospective cohort study (n = 166) including patients with aESCC who had experienced disease progression on palliative first-line therapy. A propensity score model using inverse probability of treatment weighting (IPTW) was implemented for comparative efficacy analysis of overall survival (OS) in patients with second-line + ASC (n = 92, 55%) versus ASC alone (n = 74, 45%). RESULTS: The most frequent second-line regimens used were docetaxel (36%) and paclitaxel (18%). In unadjusted primary endpoint analysis, second-line + ASC was associated with significantly longer OS compared with ASC alone [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35–0.69, p < 0.0001]. However, patients in the second-line + ASC group were characterized by more favorable baseline features including a better Eastern Cooperative Oncology Group (ECOG) performance status, a longer first-line treatment duration and lower C-reactive protein levels. After rigorous adjusting for baseline confounders by re-weighting the data with the IPTW the favorable association between second-line and longer OS weakened but prevailed. The median OS was 6.1 months in the second-line + ASC group and 3.2 months in the ASC group, respectively (IPTW-adjusted HR = 0.40, 95% CI: 0.24–0.69, p = 0.001). Importantly, the benefit of second-line was consistent across several clinical subgroups, including patients with ECOG performance status ⩾1 and age ⩾65 years. The most common grade 3 or 4 adverse events associated with palliative second-line therapy were hematological toxicities. CONCLUSION: This real-world study supports the concept that systemic second-line therapy prolongs survival in patients with aESCC

Recent Advances in Pancreatic Cancer: Novel Prognostic Biomarkers and Targeted Therapy—A Review of the Literature

Pancreatic adenocarcinoma carries a devastating prognosis. For locally advanced and metastatic disease, several chemotherapeutic regimens are currently being used. Over the past years, novel approaches have included targeting EGFR, NTRK, PARP, K-Ras as well as stroma and fibrosis, leading to approval of NTRK and PARP inhibitors. Moreover, immune check point inhibitors and different combinational approaches involving immunotherapeutic agents are being investigated in many clinical trials. MiRNAs represent a novel tool and are thought to greatly improve management by allowing for earlier diagnosis and for more precise guidance of treatment

Comparison of gemcitabine plus oxaliplatin versus gemcitabine plus nab‐paclitaxel as first‐line chemotherapy for advanced pancreatic adenocarcinoma: A single‐center retrospective analysis

Abstract Background Pancreatic cancer is mostly diagnosed in an advanced stage and treated with systemic therapy with palliative intent. Nowadays, the doublet chemotherapy of Gemcitabine and nab‐paclitaxel (Gem‐Nab) is one of the most frequently used regimens worldwide, but is not ubiquitarily available or reimbursed. Therefore, we compared the clinical efficacy of Gem‐Nab to a historical control of patients treated with gemcitabine and oxaliplatin (Gem‐Ox) at our tertiary cancer center, which was the standard treatment prior to the introduction of FOLFIRINOX. Methods This single‐center retrospective real world study includes 121 patients diagnosed with locally advanced or primary metastatic pancreatic adenocarcinoma who were treated with chemotherapy doublet, with either Gem‐Nab or Gem‐Ox in palliative first‐line. Survival rates were analyzed using the Kaplan–Meier method, and comparisons were made with log‐rank tests. Gem‐Ox was considered as standard first line therapy at our institution for patients who were deemed fit for doublet chemotherapy between the years 2006 to 2012. These patients were compared to a cohort of patients treated with the new standard first‐line therapy of Gem‐Nab between 2013 and 2020. Results A total of 554 patients with pancreatic cancer of all stages were screened, and 73 patients treated with Gem‐Nab and 48 patients treated with Gem‐Ox in the palliative first‐line setting were identified and included in this analysis. Patients receiving Gem‐Ox had a statistically significantly better performance score (ECOG PS) when compared to the Gem‐Nab group (Odds ratio (OR) 0.28, 95% CI 0.12–0.65, p = 0.005), more often suffered from locally advanced than metastatic disease (OR 3.10, 95% CI 1.27–7.91, p = 0.019) and were younger in age (OR 0.95, 95% CI 0.91–0.99, p = 0.013). Median overall survival (OS) of the whole study cohort was 10.3 months (95% CI 8.5–11.6). No statistically significant difference in OS could be observed between the Gem‐Nab and the Gem‐Ox cohort (median OS: 8.9 months (95% CI 6.4–13.5) versus 10.9 months (95% CI 9.5–13.87, p = 0.794, HR 1.27, 95% CI 0.85–1.91)). Median progression‐free survival (PFS) was 6.8 months in the entire cohort (95% CI 4.9–8.4). No statistically significant difference in PFS could be observed between the Gem‐Nab and the Gem‐Ox cohort (median PFS: 5.8 months (95% CI 4.3–8.2) versus 7.9 months (95% CI 5.4–9.5) p = 0.536, HR 1.11, 95% CI 0.74–1.67). Zero‐truncated negative binomial regressions on OS and PFS adjusting for gender, age, performance status (ECOG PS), and CA19‐9 levels yielded no significant difference between Gem‐Nab or Gem‐Ox. Conclusion From our analysis, we could evidence no difference in outcome parameters in this retrospective analysis despite the worse prognostic pattern for GemOX. Therefore, we suggest Gem‐Ox as potential first line treatment option for inoperable locally advanced or metastatic pancreatic cancer, especially if Gem‐Nab is not available

Novel models for prediction of benefit and toxicity with FOLFIRINOX treatment of pancreatic cancer using clinically available parameters.

BACKGROUND:Despite modern chemotherapy regimens, survival of pancreatic cancer patients remains dismal. Toxicity is a major concern and it is a challenge to upfront identify patients with the highest benefit from aggressive polychemotherapy. We aimed to evaluate ORR and side effects of the FOLFIRINOX regimen, highlighting dose modification and to explore possible prognostic response factors as a clinical tool. METHODS:This retrospective study includes 123 patients with metastatic PC that were treated with FOLFIRINOX between the years 2007 to 2016 in a single academic institution. Survival rates were analysed using the Kaplan-Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses. RESULTS:Median age at diagnosis was 64 years (47-78 years), 71 (57, 7%) were male and the majority had an ECOG performance status of 0 or 1 (63 patients; 83.7%). After a median follow up of 17.8 months, median progression free survival (PFS) and overall survival (OS) were 5.7 (4.55-6.84; 95%CI) and 11.8 months (9.35-14.24; 95%CI) respectively. Overall response rate with FOLFIRINOX was 34.9% and stable disease rate was 21.9%. Regarding Grade 3/4 side effects, 62 events, were reported in 37 patients. Looking at risk factors e.g. patient characteristics, tumor marker, inflammatory markers and body composition multivariate analyses proved CEA >4 elevation and BMI > 25 at the time point before palliative chemotherapy to be independent negative prognostic factors for OS. Grouping patients with no risk factor, one or two of these risk factors we analyzed a median OS of 17.4 moths, 9.6 months and 6.7 months (p<0.001) respectively. In addition we identified thrombocytosis and low BMI as predictors of early toxicity. CONCLUSION:This study identifies two easily available factors influencing overall survival with FOLFIRINOX therapy. By combining these two factors to create a score for OS, we propose a prognostic tool for physicians to identify patients, who are unlikely to benefit more from FOLFIRINOX or likely to experience toxicity