Discussion
NSCLC, toxicities, death
NSCLC
In this phase IIa study, rezivertinib showed promising efficacy and a manageable safety profile in the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with There are three third-generation EGFR TKIs available in the People’s Republic of China for advanced NSCLC. Osimertinib, the first third-generation irreversible EGFR TKI, significantly improved the PFS and OS versus first-generation EGFR TKIs gefitinib or erlotinib in patients with The third-generation EGFR TKIs revealed the optimal subgroup efficacy based on patients’ Compared with the first- or second-generation EGFR TKIs, the third-generation EGFR TKIs have improved CNS efficacy. In the FLAURA study, osimertinib reduced the risk of CNS progression or death while compared with the first-generation EGFR TKI gefitinib/erlotinib with an HR of 0.48 (95% CI: 0.26–0.86; Rezivertinib is one of the novel third-generation EGFR TKIs; the phase IIa study results were consistent with the previous phase I study [The safety profile of rezivertinib was favorable without new safety signals. Here we would like to discuss three aspects of safety profile. Firstly, dermatological and gastrointestinal toxicities were common for the first-/second-generation EGFR TKIs and osimertinib in the global FLAURA study [There are limitations to this phase IIa study. Firstly, the sample size was limited to only 43 patients and a strict randomized trial with a larger sample size is needed to further confirm the potential efficacy of rezivertinib. Encouragingly, a phase III REZOR study comparing rezivertinib with gefitinib in the first-line setting is ongoing, and the patient enrollment has been completed (NCT03866499). Secondly, there might be a potential bias while comparing with other ethnic patients since this phase IIa study was conducted among Chinese patients only.