An incidence of disease flare occurring after EGFR-TKI discontinuation might predict a poor survival [32] and [33], which suggests that the continuation beyond progression of EGFR-TKIs is a reasonable strategy.

In this matched-pair case-control study, the overall response rates in the gefitinib-integrated and chemotherapy alone groups were 9.1% and 6.45%, respectively (P > .05). The corresponding disease-control rates were 39.39% and 30.30%, respectively (P > .05). Such low response rates might be owing to the acquired resistance to EGFR-TKI and chemotherapy in heavily pretreated patients as they had all received prior EGFR-TKI and one or two lines GSK269962 in vivo of chemotherapy. Furthermore, the median OS (10.36 vs 7.9 months) and PFS (4.15 vs 3.25 months) did not significantly differ between the gefitinib-integrated and chemotherapy groups. In our study enrolling metastatic EGFR-mutated lung adenocarcinoma patients who had failed prior EGFR-TKI and platinum-based chemotherapy, no significant survival differences were observed between the gefitinib plus chemotherapy and chemotherapy alone groups either. Although this was a retrospective study

rather than Obeticholic Acid clinical trial a clinical trial, the results were comparable since the matched-pair case-control design was employed, and selected patients were well matched between the two groups regarding age, sex, ECOG PS, EGFR mutation, PFS from previous EGFR-TKI treatment, and metastasis status. On the basis of those limited

data, several clinical trials were designed, including the ongoing phase III randomized Casein kinase 1 multicenter IMPRESS (A Study of IRESSA Treatment Beyond Progression in Addition to Chemotherapy Versus Chemotherapy Alone) trial to assess the safety and efficacy of continuing gefitinib at 250 mg in addition to chemotherapy versus chemotherapy alone in patients with EGFR-mutated NSCLC who have progressed on first-line gefitinib. The results of this study are being expected. Nevertheless, the present retrospective study cannot replace a randomized clinical trial since selection bias might exist in other unmeasured clinical factors and the evaluation timeline was not strictly predetermined. Furthermore, the study cohort was limited, and other important issues such as dose intensity, toxicity profiles, and treatment compliance were not considered. In conclusion, to the best of our knowledge, this is the first matched-pair case-control study that evaluated and compared the outcomes between gefitinib-integrated regimens and chemotherapy alone in EGFR-mutated lung adenocarcinoma patients who had failed prior EGFR-TKI and chemotherapy treatments. Our analysis demonstrated that heavily pretreated patients tended to achieve improved PFS and OS if treated with chemotherapy plus gefitinib.