The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.
Our meta-analysis of individual patient data suggests no differences in efficacy between cisplatin and carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.
Background
Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors.
Materials and Methods
Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups.
Results
A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre‐existing AIDs were not significantly related with progression‐free survival and overall survival.
Conclusion
This study quantifies the increased risk of developing irAEs in patients with pre‐existing AIDs who had to be treated with anti‐PD‐1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the “hot topics” in gender‐related differences in immuno‐oncology.
Implications for Practice
Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune‐related adverse events (irAEs) in patients with pre‐existing AIDs who had to be treated with anti‐programmed death‐1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre‐existing autoimmune disease.
In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.
Platinum-based chemotherapy remains the standard-of-care for most patients affected by advanced non-small cell lung cancer (NSCLC). The platinum compounds currently used in NSCLC are cisplatin and carboplatin. The availability of new generation drugs has led to the adoption of schedules with lower doses of platinum compounds leading to increased tolerability. Several data suggest that third generation cisplatin-based regimens are slightly superior to carboplatin-based chemotherapy, with a different safety profile, and so cisplatin should remain the standard reference for the treatment of selected patients with advanced NSCLC. Recent evidence emphasized that the optimal number of first-line platinum cycles should be four for any NSCLC histology. New platinum compounds and the use of functional genomics to deliver platinum drugs as personalised medicine, are being investigated. Here we review the current status of cisplatin and carboplatin regimens looking to the future role of platinum compounds in advanced NSCLC patients.
With the exception of advanced NSCLC, prospective elderly-specific studies are lacking. Available data suggest that outcomes in the fit elderly mirror results observed in younger patients, although toxicity is generally worse.
LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe the molecular mechanism of action of erlotinib.2. Define clinical and molecular predictors of response to erlotinib.3. Describe the clinical trials performed with erlotinib in NSCLC and underline future clinical development of this drug in the treatment of NSCLC.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME
ABSTRACT
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