Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor: A retrospective multicenter study of its real‐world efficacy and safety in advanced/recurrent non‐small cell lung carcinoma

Abstract

Background Osimertinib is recommended for T790M mutation‐positive advanced non‐small cell lung cancer (NSCLC) resistant to first‐ and second‐generation epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs). Recently, some reports exist on the real‐world use of osimertinib; however, reports involving third/later‐line use are few. Hence, this study was conducted to evaluate the efficacy and safety of osimertinib used in various treatment lines for T790M‐positive NSCLC patients. Methods This retrospective, observational, multicenter study included T790M‐positive advanced/recurrent NSCLC patients treated with osimertinib from May 2016 to March 2018. The clinical characteristics, efficacy, and adverse events were retrospectively investigated. The Kaplan‐Meier method was used to analyze progression‐free survival (PFS) and overall survival (OS). PFS‐associated clinical characteristics were evaluated using the Cox proportional hazards model. Results The objective response rate (ORR) and disease control rate (DCR) were 60.7% and 91.1%, respectively; the median PFS was 11.0 months. There were no significant differences in the median PFS for patients treated with osimertinib as second‐line and third−/later‐line (14.5 vs. 11.0 months respectively, P = 0.327). Analysis using the Cox proportional hazards model for clinical features affecting PFS also revealed no significant factors. Adverse events of grade ≥ 3 were reported in 15 patients (26.8%); the most common were anemia (n = 3) and cutaneous toxicity (n = 3). Grade 4 neutropenia was observed in one patient; any‐grade pneumonitis was observed in six patients (10.7%), including one with grade 3 pneumonitis. Conclusions Osimertinib demonstrated efficacy even when administered as third−/later‐line treatment to NSCLC patients. Osimertinib‐related pneumonitis was observed more frequently than previously reported. Key points Significant findings of the studyOsimertinib shows efficacy even as later‐line treatment in T790M mutation‐positive NSCLC patients previously treated with EGFR‐TKIs. However, the incidence of ≥ grade 3 adverse events, especially pneumonitis, was higher than that previously reported by other studies. What this study addsOsimertinib was approved for previously EGFR‐TKI‐treated EGFR T790M‐positive NSCLC. With the increasing frequency of its use as first‐line treatment, this study provides valuable evidence for the efficacy and safety of osimertinib for previously EGFR‐TKI‐treated NSCLC.

The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: a Turkish Oncology Group Study

“…In this context, the survival outcomes of other real-life studies varied between median 9.4 and 14.5 months of PFS, in the second-line treatment of advanced NSCLC with T790M mutation (9)(10)(11)(12)(13)(14). The Spanish Lung Cancer Group reported a median of 9.4 months PFS in 155 patients, and this was a very close to the PFS reported in the pivotal phase 3 trial (6, 10).…”

“…The Spanish Lung Cancer Group reported a median of 9.4 months PFS in 155 patients, and this was a very close to the PFS reported in the pivotal phase 3 trial (6, 10). Other studies from different regions and ethnicities like China, Japan, France, and Poland demonstrated slightly better real-life outcomes than the AURA3 trial with approximately median 11-14 months of PFS (9,(11)(12)(13)(14). In general, outcomes of reallife experiences with the different classes of drugs just like cytotoxic chemotherapy, barely exceed the success of pivotal studies.…”

The Real-Life Efficacy And Safety of Osimertinib In Pretreated Advanced Non-Small Cell Lung Cancer Patients With T790M Mutation: A Turkish Oncology Group Study

“…In this context, the survival outcomes of other real-life studies varied between median 9.4 and 14.5 months of PFS, in the second-line treatment of advanced NSCLC with T790M mutation (9)(10)(11)(12)(13)(14). The Spanish Lung Cancer Group reported a median of 9.4 months PFS in 155 patients, and this was a very close to the PFS reported in the pivotal phase 3 trial (6, 10).…”

“…The Spanish Lung Cancer Group reported a median of 9.4 months PFS in 155 patients, and this was a very close to the PFS reported in the pivotal phase 3 trial (6, 10). Other studies from different regions and ethnicities like China, Japan, France, and Poland demonstrated slightly better real-life outcomes than the AURA3 trial with approximately median 11-14 months of PFS (9,(11)(12)(13)(14). In general, outcomes of reallife experiences with the different classes of drugs just like cytotoxic chemotherapy, barely exceed the success of pivotal studies.…”

Incidence and Risk Factors of Pneumonitis in Patients with Non-Small Cell Lung Cancer: An Observational Analysis of Real-World Data

“…The approval of targeted therapies including third-generation tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has led to improved longterm survival, relegating conventional chemotherapy to a secondary role [4,5]. However, these targeted therapies are associated with a potentially fatal treatment-induced adverse event (AE), pneumonitis, which has been documented in patients treated with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs [6][7][8][9], epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) [10][11][12], and anaplastic lymphoma kinase (ALK) inhibitors [13]. Symptoms typically associated with pneumonitis resulting from the use of targeted NSCLC therapies include cough, dyspnea, fever, chest pain, and hypoxia, accompanied by pulmonary infiltrates that are evident in chest computer tomography (CT) images [14,15].…”