OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
INTRODUCTION: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data. METHODS: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria. RESULTS: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70-93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14-96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients. CONCLUSIONS: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity.
BACKGROUND: Non-small cell lung cancer (NSCLC) has undergone a major change in the last decade in terms of survival and prognosis due to the introduction of new drugs in the last 10 years. One of the drugs with the most promising preliminary results in NSCLC are PARP inhibitors (iPARPs), whose clinical trials have very heterogeneous results. The use of iPARPs in NSCLC may lead to increased survival in several selected patients, and their use may become a standard in the coming years. However, there is currently controversy about the efficacy and safety of these drugs in NSCLC. Therefore, future studies are needed to evaluate their role in these tumours. The aim of this review is to evaluate the efficacy and safety of iPARPs in the treatment of NSCLC. METHODS: We performed a systematic review with meta-analysis using the different clinical trials (PubMed, COCHRANE, Science Direct, EMBASE and the clinical trial registry) that evaluated the efficacy and safety of iPARP in NSCLC by PRISMA criteria. The primary endpoint was to evaluate the efficacy of iPARPs in the treatment of NSCLC through overall and progression-free survival (OS and PFS). Two authors independently reviewed the articles and abstracts (A.O.H. and J.R.R.), with subsequent confirmation by a third independent reviewer (E.B.M.). The heterogeneity of the included studies in the meta-analysis was assessed by using the I2 statistic. RESULTS: A total of 14 articles were included for analysis (2,651 patients). A total of 1,503 patients were randomised in iPARP arms and 1,148 patients were included in control arms. Three clinical trials were conducted in localised or locally advanced NSCLC and 11 in advanced or metastatic stages. The global OS of the meta-analysis showed a hazard ratio (HR) of 0.85 [95% confidence interval (CI): 0.74-0.97] with a heterogeneity (I2) of 0% (P=0.84). PFS showed a HR of 0.93 (95% CI: 0.74-1.17) with an I2=51% (P=0.07). The overall adverse event rate (grade 1-5) was similar in both iPARP and placebo arms. CONCLUSIONS: iPARPs are a future promising in the treatment of NSCLC in terms of efficacy and safety. Proper patient selection [homologous recombination deficiency (HRD) positive] is key for future clinical trials. The studies conducted to date open a new approach for a novel treatment modality in NSCLC.
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Patient Selection , Randomized Controlled Trials as Topic
Introduction COVID-19 disease has caused a global health and economic crisis. The introduction of the different COVID-19 vaccines has resulted in a significant decrease in the morbidity and mortality associated with this disease. Adverse effects have been reported, including cardiological ones such as myocarditis or pericarditis after administration. Likewise, tyrosine kinase inhibitor drugs such as osimertinib used in lung cancer patients with epidermal growth factor receptor (EGFR) mutation are associated with heart failure or prolongation of the QT interval. Case report 62-year-old woman diagnosed in September 2019 of lung adenocarcinoma stage IV with bilateral lung and lymph node involvement, carrier of an EGFR mutation (Ex19Del) on treatment with osimertinib. She attended emergency department for fever and hypotension 24 h after administration of the third dose of Moderna® COVID-19 vaccine in the context of acute myocarditis with evidence of severe left ventricular (LV) dysfunction in cardiogenic shock. She required vasoactive support, non-invasive mechanical ventilation, corticotherapy, immunoglobulins and subsequent ventricular support with Impella, with improvement of the clinical picture after 3 days. Cardiac magnetic resonance imaging (MRI) showed evidence of global myocardial oedema compatible with acute myocarditis. Coronary CT showed a lesion in the anterior descending coronary artery requiring revascularization. A few days later, she presented febrile symptoms with isolation of Staphylococcus aureus in the central line catheter and antibiotherapy with cloxacillin was started, with subsequent resolution of the infectious symptoms. Conclusion This is an exceptional and controversial case of fulminant myocarditis probably related to the Modern COVID-19 vaccine in a patient diagnosed with metastatic lung adenocarcinoma on treatment with osimertinib. An increasing number of cases of myocarditis and pericarditis have been reported following vaccination with COVID-19 mRNA vaccines. In addition, retrospective data have shown an increased risk of QT prolongation and heart failure in patients treated with tyrosine kinase inhibitors. Hence, the need for close monitoring of cardiac function during treatment of these patients. Future studies will be necessary to evaluate unknown adverse reactions of these vaccines and their possible interaction with other antineoplastic drugs.
Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system's involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669-61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, and is now responsible for as many deaths as melanoma. Immunotherapy has changed the therapeutic landscape of advanced CSCC after the FDA approval of anti-PD1 molecules for the treatment of locally advanced and metastatic CSCC. However, roughly 50% of patients will not respond to this systemic treatment and even those who do respond can develop resistance over time. The etiologies of primary and secondary resistance to immunotherapy involve changes in the neoplastic cells and the tumor microenvironment. Indirect modulation of immune system activation with new therapies, such as vaccines, oncolytic viruses, and new immunotherapeutic agents, and direct modulation of tumor immunogenicity using other systemic treatments or radiotherapy are now under evaluation in combined regimens. The identification of predictors of response is an important area of research. In this review, we focus on the features associated with the response to immunotherapy, and the evaluation of combination treatments and new molecules, a more thorough knowledge of which is likely to improve the survival of patients with advanced CSCC.
Background. Immunotherapy represents one of the fundamental treatments in the management of some types of cancer, especially malignant melanoma. Toxicity derived from increased immune system activity can manifest in multiple organs and systems. We present a case of hematological toxicity, manifested as hemophagocytic syndrome (HPS), which was successfully treated with an anti-interleukin-6 antibody (tocilizumab). Case Report. This case presents a 75-year-old woman diagnosed with metastatic choroidal melanoma, refractory to several lines of treatment. After the failure of the previous lines, ipilimumab was started. After the third dose, she developed grade 2 thrombocytopenia and anemia accompanied by elevated levels of ferritin, triglycerides, and decreased fibrinogen. Hemophagocytosis was observed in the bone marrow biopsy, and a PET-CT showed splenomegaly with increased metabolism. Treatment was based on high doses of corticosteroids and tocilizumab. Four days after the start of treatment, progressive clinical and analytical improvement was observed, achieving total remission of the condition. Discussion. HPS induced by immunotherapy is due to an immunorelated cytokine storm syndrome (CSS). The administration of the anti-interleukin-6 receptor antibody drug acted on this cytokine cascade, leading to stabilization and subsequent remission. For this reason, the use of tocilizumab should be part of the immunotherapy-induced HPS treatment algorithm.
