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- Title
Post-Progression Analysis of EGFR -Mutant NSCLC Following Osimertinib Therapy in Real-World Settings.
- Authors
Attili, Ilaria; Corvaja, Carla; Spitaleri, Gianluca; Trillo Aliaga, Pamela; Del Signore, Ester; Passaro, Antonio; de Marinis, Filippo
- Abstract
Simple Summary: This study is a real-world study on a large cohort of patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progressed on osimertinib, focusing on access to subsequent treatments and progression patterns, including central nervous system (CNS) progression. Almost half of these patients had no access to further treatments due to worsening of clinical conditions or death. The outcomes of standard platinum-based chemotherapy were dismal and in line with those reported in the literature. Notably, intracranial disease progression was a rare event during osimertinib, whereas it occurred in half the patients during standard chemotherapy. Overall, the data highlight the clinical unmet needs in the treatment sequencing of single agent osimertinib and platinum-based chemotherapy alone, confirming the role of combination approaches and treatments in improving CNS control. Background: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. Methods: Patients with EGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. Results: A total of 220 patients received indication for osimertinib in the study period; n = 176 had adequate follow-up data. Overall, n = 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13–18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients, n = 8 received experimental treatments, and n = 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2–5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2–5) and 10 (95% CI 6–15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2–7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. Conclusions: Access to subsequent treatments and CNS progression are confirmed unmet needs in EGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue.
- Subjects
HEALTH services accessibility; RESEARCH funding; PROTEIN-tyrosine kinase inhibitors; BRAIN; RETROSPECTIVE studies; TREATMENT effectiveness; DESCRIPTIVE statistics; TREATMENT duration; CANCER chemotherapy; LUNG cancer; GENETIC mutation; CENTRAL nervous system diseases; CONFIDENCE intervals; PROGRESSION-free survival; EPIDERMAL growth factor receptors; DISEASE progression; PLATINUM; OVERALL survival
- Publication
Cancers, 2024, Vol 16, Issue 14, p2589
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16142589