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

Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population:a retrospective cohort study

Background: To investigate effect and toxicity of immune checkpoint inhibition (ICI) in a Danish real-life non-small cell lung cancer (NSCLC) population. By including patients underrepresented in clinical trials, such as those with brain metastasis (BM), higher age, more comorbidity and poorer performance status (ECOG), comparison of unselected patients to clinical trial populations is possible. Material and methods: Real life data were gathered from 118 consecutive NSCLC patients with incurable NSCLC treated with ICI at the Department of Oncology at the University Hospital of Odense, Denmark from September 2015 to April 2018. Immune-related adverse events (irAEs) grades 3–5 were registered prospectively during the same period. Additional patient related data were obtained retrospectively from patients' files. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan–Meier estimates, the log-rank test and cox regression analysis performed for factors affecting survival. Results: Median age for patients was 66 years (IQR 59–71) and 62 years (range: 55–64) for those with BM. Females 63%; adenocarcinoma (AC)/squamous/others 69%/23%/8%; ECOG ≥ 2 10%; bone/brain/liver metastases 36%/18%/15%; PD-L1 (TPS) p = .005). For patients with BM, the median OS was 8.2 months (HR 1.38, [95% CI: 0.7–2.5], p = .37). Twenty-four percent of patients terminated ICI due to irAE grades 3–5 alone (grade 5, n  =  1), which were not associated with higher age or BM. Conclusions: OS and PFS were comparable to clinical trial reports. Long-lasting remission is also possible in patients with BM. Real-life populations have higher rates of irAE grades 3 and 4 than reported in clinical trials, but it does not seem to impact median OS.</p

Incidence, risk factors and clinical outcome of venous thromboembolism in non-small cell lung cancer patients receiving immune checkpoint inhibition

Background: Besides the cancer itself, venous thromboembolism (VTE) is the leading cause of death in cancer patients receiving outpatient chemotherapy (CT). Data on VTE development and impact on treatment course and outcome in real-life NSCLC patients receiving immune check-point inhibitors (ICI) is currently sparse. More knowledge within this area is warranted due to the emerging use of ICI in clinical practice. Objectives: To quantify risk of VTE and recurrent VTE in NSCLC patients receiving ICI. Explore the clinical impact of VTE on ICI course and survival and explore potential risk factors for VTE. Patients/methods: Patients with advanced/metastatic NSCLC treated with an immune checkpoint inhibitor (ICI) at the University Hospital of Odense, Denmark during 2015–2018 were identified and data gathered retrospectively from electronic medical records (n = 118). All patients had finished ICI at the time of data-cut off. Baseline Khorana Score (KRS) was calculated within one week prior to ICI initiation. Based on follow-up data cumulative incidence of VTE and its impact on outcome and survival was performed using Kaplan Meier and cox-regression hazard estimation. Results: Risk of VTE was 8% during ICI and 15% at any time point after ICI initiation. Cumulative incidence rates of VTE at 1, 3, 6 and 18 months after first ICI was 1.7%, 5.2%, 6.9% and 13.8% respectively. Median time to VTE during ICI was 2.3 months [IQR 0.6–5.4]. Having VTE during ICI lead to discontinuation of ICI in 78% of cases, most due to fatal PE. History of VTE before onset of ICI was a significant risk factor for recurrent VTE during ICI (24% within this subgroup) despite use of anticoagulant therapy. Conclusions: The incidence and impact of VTE during ICI for real-life NSCLC patients is not negligible with almost 10% developing VTE leading to termination of further ICI in the majority of cases - many due to fatal PE. The risk of recurrent anticoagulant resistant VTE in patients with known VTE during ICI is also considerable, which calls for better management and prevention of VTE including development of treatment specific VTE risk assessment models

Effect and Tolerability of Immunotherapy in Patients with NSCLC with or without Brain Metastasis

Sparse data exist on immune checkpoint inhibition (ICI) in NSCLC patients with brain metastasis (BM), especially for those with no local therapy (LT) (whole brain radiation therapy (WBRT), stereotactic RT (SRT) or neurosurgery) preceding ICI. Our aims were to investigate the prevalence of BM, rate of intracranial response (ICR), and survival and quality of life (QoL) in real-life patients with advanced NSCLC undergoing palliative ICI. This was a prospective non-randomized study (NCT03870464) with magnetic resonance imaging of the brain (MR-C) performed at baseline resulting in a clinical decision to administer LT or not. ICR evaluation (MR-C) at week 8&ndash;9 (mRECIST criteria) for group A (LT) and group B (untreated) was assessed. Change in QoL was assessed using EQ-5D-5L. Of 159 included patients, 45 (28%) had baseline BM. Median follow-up was 23.2 months (IQR 16.4&ndash;30.2). Of patients in group A (21) and B (16), 16/37 (43%) had symptomatic BM. ICR was 8/21, 38% (complete or partial response) for group A versus 8/16, 50% for group B. No statistical difference in median overall survival of patients with BM (group A: 12.3 (5.2-NR), group B: 20.5 months (4.9-NR)) and without (22.4 months (95% 16.2&ndash;26.3)) was obtained. Baseline QoL was comparable regardless of BM, but an improved QoL (at week 9) was found in those without BM. Patients with NSCLC and BM receiving ICI had long-term survival comparable to those without BM

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