The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications. Among these, a spectrum of endocrine disorders has been also reported. This manuscript focuses particularly on endocrine disorders induced by immuno-checkpoint inhibitors employed in NSCLC, in order to suggest the strategies for their diagnosis and effective management.
Capecitabine is an oral fluoropyrimidine which is transformed to 5-Fluorouracil inside tumor cells, where it achieves high drug concentrations. Capecitabine is an active drug diffusely utilized in the treatment of various types of tumors, such as breast, colorectal, gastric, head and neck carcinoma. In our experience, capecitabine-induced hypertriglyceridemia does not seem to be a rare adverse effect as it is observed in 10% of treated patients. It is necessary to monitor the lipidic profile of patients treated with capecitabine also in consideration of the frequent presence of comorbidities in cancer populations, the concomitant toxicity related to other drugs used in combination regimens, and cardiovascular effects characteristic of biological target therapy.
For advanced disease, palliation and preserving patients QoL are still the primary goal of treatment. Therefore, differing toxicity profiles are often a deciding factor in first-line and also maintenance setting for non-squamous NSCLC. Special attention is necessary to renal function and drugs' nephrotoxicity. Moreover, it is to consider the specific AEs of drugs classes: hypertension, bleeding, and proteinuria, for anti-VEGF therapy; skin toxicity, diarrhea, interstitial lung disease for TKIs; vision disorders, and hepatotoxicity for ALK-inhibitor. It is important to select patients for a treatment on the basis of their comorbidities and the presence of risk factors.
Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment ( p < 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.
With increasing life expectancy over the last several decades, the incidence of lung cancer is increasing in the elderly population too. In clinical practice about 50% of lung cancers were diagnosed in patients older than 65 years and about 30-40% of lung cancer patients are 70 years old or more. Treatment of elderly patients with non-small-cell lung cancer (NSCLC) represents a challenge in clinical practice, because these patients are not eligible for aggressive therapies for the age-related reduction of functional reserve of many organs and comorbidities. Areas covered: The activity and safety of small molecules for the treatment of NSCLC harbouring EGFR mutations or ALK rearrangement are reviewed and discussed here, using evidence from clinical trials. Expert commentary: Age alone should not dictate treatment-related decisions for elderly patients with advanced NSCLC. Some evidence has shown that the only relevant factor for survival outcome in the elderly is performance status and organ functions both with chemotherapy and targeted therapy too. Considering the toxicity profile of tyrosine kinase inhibitors, these small molecules are particularly attractive to treat elderly patients, who could experience potentially more toxicity from chemotherapy. Studies specifically addressed to evaluate the activity of targeted therapy are still more limited.
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