A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903

Abstract

Background: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear. Patients and methods: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses. Results: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P ¼ 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P ¼ 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001). Conclusions: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.

Risk Stratification Using a Novel Nomogram for 2190 EGFR-Mutant NSCLC Patients Receiving the First or Second Generation EGFR-TKI

“…No prospective study comparing osimertinib with 2G EGFR-TKIs is available. The only retrospective study demonstrated that osimertinib and afatinib showed similar OS [ 47 ]. Because it has a high price and offers no survival benefit in an Asian subgroup [ 11 ], osimertinib is not fully reimbursed in Asian countries, including Taiwan.…”

First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

“… 40 Third, the recent advance of third-generation EGFR-TKIs also challenges the role of afatinib as a front-line treatment. Interestingly, a recent study of a Japanese cohort demonstrated that afatinib resulted in better OS compared with osimertinib, 41 though this issue remains largely unsettled.…”

Afatinib Treatment Alone or with Bevacizumab in a Real-World Cohort of Non-Small Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Mutation

“…Thirdly, the recent administration of third-generation osimertinib monotherapy as well as the combination of osimertinib and bavaciumab also challenges the role of afatinib on the treatment of advanced EGFR -mutant NSCLC [ 36 , 37 ]. However, a recent Japanese real-world cohort of NSCLC patients demonstrated an improved OS of front-line afatinib compared to osimertinib treatment [ 38 ] and the true benefit of adding bevacizumab to front-line osimertinib remains largely unsettled based on some small early-phase trials [ 37 ].…”