*4.2. Comparison with Previous Studies*

Previous reports related to EGFR inhibitors showed consistent findings with the current study. A recent meta-analysis of 90 retrospective or prospective cohort studies and clinical trials showed the comparable effect of gefitinib vs. erlotinib [20]. The RR (95% CI) for ORR and HR (95% CI) for PFS were 1.05 (1.00–1.11) and 1.00 (0.95–1.04), respectively [20]. Another network meta-analysis of 11 clinical trials also showed the similar PFS between gefitinib and erlotinib [21]. However, unlike our findings, the third-generation EGFR inhibitor osimertinib was found to have a longer PFS (HR 0.71, 95% CI 0.54–0.95), and the significant difference between the second-generation EGFR inhibitor afatinib and standard of care (either gefitinib or erlotinib) was not observed (HR 0.96, 95% CI, 0.86–1.17) [21].

In a large medical chart review of 1471 participants with ALK-positive NSCLC among a total of 27,375 recorded subjects from seven countries, crizotinib showed a significant improvement in complete response (odds ratio (OR) = 2.65, 95% CI = 1.69–4.15) and reduction of recurrence/progression (odds ratio = 0.38, 95% CI = 0.24–0.59) compared to controls [22]. Also, a recent network meta-analysis of ALK inhibitors showed consistent findings among treatments in both ORR and PFS outcomes [23]. In Fan et al.'s study, a remarkable improvement in ORR was shown: the ORs (95%CI) for crizotinib, ceritinib, and alextinib were 11.69 (4.29–36.56), 7.85 (3.44–19.27), and 6.04 (3.33–11.71), compared to chemotherapy, respectively [23]. The superior efficacy of alectinib in PFS might be associated with the resistance to crizotinib among ALK-positive NSCLC patients, which reduces therapeutic response to crizotinib [24,25]. Although ceritinib is also a second-generation ALK inhibitor, our study showed that there is no signicant difference in the efficacy between ceritinib and crizotinib. Similarly, the recent meta-analyses of pooled estimates reported that crizotinib might have higher ORR [66% (58–74%) vs. 52% (38–66%)] and longer PFS [9.27 months (8.28–10.26) vs. 5.92 months (4.36–7.48)] than ceritinib,

although no statistical test was performed [26]. It remains unclear why ceritinib did not show a superior efficacy unlike alectinib.
