Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown. METHODS: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used. RESULTS: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR-NR) and was 5.5 (interquartile range: 2.4-10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3). CONCLUSIONS: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib.

Real-World Outcomes With Lurbinectedin in Second-Line Setting and Beyond for Extensive Stage Small Cell Lung Cancer.

BACKGROUND: Lurbinectedin has emerged as a potential treatment option for relapsed small cell lung cancer (SCLC). While clinical trials have demonstrated its efficacy and safety, real-world data are limited. This study aimed to evaluate the safety and efficacy of lurbinectedin in a real-world setting, focusing on its use as a second-line agent and beyond in SCLC patients. METHODS: A retrospective analysis was conducted on 90 patients who received lurbinectedin between June 2020 and June 2022 within the Mayo Clinic Health System. Of these, 50 patients received lurbinectedin as a second-line agent, and 14 patients received it as a third-line or later agent. The primary outcomes assessed were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. RESULTS: Lurbinectedin was generally well tolerated in this real-world cohort, with a median OS of 5.1 months in the second-line cohort and 5.6 months in the third-line or later cohort. Median PFS was 2.1 months in the second-line cohort and 3.4 months in the third-line or later cohort. Adverse events were manageable, with the most common being neutropenia, anemia, fatigue, and febrile neutropenia. No treatment-related deaths or grade 5 toxicities were reported. CONCLUSION: This real-world study provides valuable insights into the safety and efficacy of lurbinectedin in relapsed SCLC. Lurbinectedin demonstrated modest efficacy and a comparable safety profile to that observed in clinical trials. However, outcomes for relapsed SCLC remain suboptimal, particularly for patients with a shorter chemotherapy-free interval and central nervous system metastases.

Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report.

INTRODUCTION: We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC. METHODS: Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022. RESULTS: Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27-123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients. Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4-542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31-90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively. CONCLUSION: One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment.

Sex Differences in All-Cause Inpatient Mortality Risk in Gastric Cancer: Nationwide Inpatient Population-Based Study.

Objective The purpose of this study is to evaluate the differences in demographic characteristics, comorbidities, and hospital outcomes in gastric cancer inpatients by sex and evaluate the risk factors for in-hospital mortality in gastric cancer inpatients by sex. Methods We conducted a cross-sectional study using the nationwide inpatient sample (NIS, 2019). Our sample included 22,415 adult inpatients (age ≥18 years) hospitalized with a primary discharge diagnosis of gastric cancer that was identified by the international classification of diseases, 10th revision (ICD-10) codes of C16.x. Independent univariate binomial logistic regression models were used to evaluate the odds ratio (OR) of predictors associated with all-cause in-hospital mortality in gastric cancer inpatients by sex. Results The total number of patients admitted with gastric cancer was 22,415, out of which 62.7% were males and 37.3% were females, with the mean age at the admission of 65.5 years and 66.4 years, respectively. While studying comorbidities, we found that 41.5% percent of all patients had gastric cancer with metastasis, and there existed a significantly higher prevalence in males (42.2% vs. 40.4% in females). Other important and statistically significant comorbid conditions that were prevalent in these patients include complicated diabetes (12.2%), obesity (12.1%), depression (8%), and alcohol abuse (3.1%). Females between 50-59 years of age were at 2.5 times increased risk of mortality compared to those less than 40 years of age (OR: 2.5; 95% CI: 1.28-4.95). Conclusion Females of the age group 50-59 years are at greater risk of all-cause inpatient mortality due to gastric cancer. Black males are at increased risk of all-cause inpatient mortality compared to White males. Gastric cancer incidence and mortality rates have been down trending with the development of screening and better treatment options, but it still continues to be a major burden on the healthcare system.