Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

SIMPLE SUMMARY: The expected change in overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) after the clinical implementation of immune checkpoint inhibitor therapy (ICI) has not been substantially investigated in large real-world cohorts outside randomized controlled trials (RCTs). In this nationwide study, we compared OS before and after the implementation of ICI and found that 3-year OS tripled from 6% to 18%. Patients receiving ICI had a lower OS than demonstrated in RCTs, except for patients with performance status (PS) 0. More than a fifth of the patients progressed early within the first six ICI cycles. Adverse prognostic factors were PS ≥ 1 and metastases to the bone and liver. ABSTRACT: Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis

Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial

Aims Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients. Methods and results This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin 100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39). Conclusion Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis

Clinical features affecting efficacy of immune checkpoint inhibitors in pretreated patients with advanced NSCLC: a Danish nationwide real-world study

Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain subgroups such as patients with older age, poor performance status (PS), and severe comorbidity are underrepresented in the randomized controlled trials (RCTs). This study aimed to assess overall survival (OS), treatment data, and clinical features affecting second- or subsequent-line ICI efficacy in an unselected, Danish, nationwide NSCLC population. Patients with advanced NSCLC who started nivolumab or pembrolizumab as second-line or subsequent-line treatment between 1 September 2015, and 1 October 2018, were identified from institutional records of all Danish oncology departments. Clinical and treatment data were retrospectively collected. Descriptive statistics and survival analyses were performed. Data were available for 840 patients; 49% females. The median age was 68 years (19% were ≥75 years), 19% had PS ≥2, and 36% had moderate to severe comorbidity. The median OS (mOS) was 12.2 months; 15.1 months and 10.0 months in females and males, respectively. The median time-to-treatment discontinuation (mTTD) and median progression-free survival (mPFS) was 3.2 and 5.2 months, respectively. Patients with PS ≥2 had a mOS of 4.5 months, mTTD of 1.1 month, and mPFS of 2.0 months. In multivariable Cox regression analysis, male sex (HR = 1.35, 95% CI 1.11–1.62), PS &gt;0 (PS 1, HR = 1.88, 95% CI 1.52–2.33; PS ≥2, HR = 4.15, 95% CI 3.13–5.5), liver metastases (HR = 1.72, 95% CI 1.34–2.22), and bone metastases (HR = 1.27, 95% CI 1.03–1.58) were significant poor prognostic OS factors. Danish real-world patients with advanced NSCLC treated with second- or subsequent-line ICI had an OS comparable to results from RCTs. Women, frail and older patients constituted a higher proportion than in previous RCTs. Clinical features associated with poor OS were male sex, PS ≥1 (in particular PS ≥2), bone-, and liver metastases