RESUMO
Purpose: Leptomeningeal metastasis (LM) is a severe complication of non-small cell lung cancer (NSCLC). In patients with NSCLC LM harboring epidermal growth factor receptor (EGFR) mutations, osimertinib is favored over alternative EGFR tyrosine kinase inhibitors (TKIs). However, the efficacy of osimertinib relative to other EGFR-TKIs is not well established for patients with LM. We aimed to compare the efficacy of EGFR-TKIs in EGFR-mutated NSCLC LM. Methods: This systematic review and meta-analysis performed according to PRISMA guidelines included studies of adult patients with EGFR-mutated NSCLC and a diagnosis of LM who received an EGFR-TKI for the treatment of LM. We searched Medline ALL, Embase, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science Core Collection. The evaluation of biases was done by using the Ottawa-Newscastle scale. The hazard ratio was used as the parameter of interest for overall survival (OS) and central nervous system-specific progression-free survival (PFS). Results: 128 publications were included with 243 patients and 282 lines of EGFR-TKI for NSCLC LM that met inclusion criteria. The median PFS in patients receiving any EGFR-TKI was 9.1 months, and the median OS was 14.5 months. In univariate analyses of the entire cohort, osimertinib treatment demonstrated significantly prolonged PFS, but not OS, compared to other EGFR-TKIs. Osimertinib demonstrated significantly prolonged PFS and OS in the subset of patients who were previously treated with EGFR-TKIs, but not in EGFR-TKI naïve patients. Conclusion: Osimertinib is associated with improved outcomes compared to other EGFR-TKIs, particularly in patients previously treated with EGFR-TKIs. An important limitation is that most patients were derived from retrospective reports. These results highlight the need for prospective studies for this difficult-to-treat patient population.
RESUMO
Cancer patients, specifically lung cancer patients, show heightened vulnerability to severe COVID-19 outcomes. The immunological and inflammatory pathophysiological similarities between lung cancer and COVID-19-related ARDS might explain the predisposition of cancer patients to severe COVID-19, while multiple risk factors in lung cancer patients have been associated with worse COVID-19 outcomes, including smoking status, older age, etc. Recent cancer treatments have also been urgently evaluated during the pandemic as potential risk factors for severe COVID-19, with conflicting findings regarding systemic chemotherapy and radiation therapy, while other therapies were not associated with altered outcomes. Given this vulnerability of lung cancer patients for severe COVID-19, the delivery of cancer care was significantly modified during the pandemic to both proceed with cancer care and minimize SARS-CoV-2 infection risk. However, COVID-19-related delays and patients' aversion to clinical settings have led to increased diagnosis of more advanced tumors, with an expected increase in cancer mortality. Waning immunity and vaccine breakthroughs related to novel variants of concern threaten to further impede the delivery of cancer services. Cancer patients have a high risk of severe COVID-19, despite being fully vaccinated. Numerous treatments for early COVID-19 have been developed to prevent disease progression and are crucial for infected cancer patients to minimize severe COVID-19 outcomes and resume cancer care. In this literature review, we will explore the lessons learned during the COVID-19 pandemic to specifically mitigate COVID-19 treatment decisions and the clinical management of lung cancer patients.
