Abstract

e21577 Background: Immunotherapy has dramatically changed the landscape of lung cancer management. However, its efficacy remains controversial in patients with activating mutations. We report retrospective analysis of clinical outcomes of advanced stage NSCLC patients with activating mutations treated with immune checkpoint inhibitors throughout their disease course. Methods: We analyze all adult patients diagnosed with advanced NSCLC in our institution between January 2014 and January 2018, and who had activating mutations in EGFR, MET, or BRAF genes or ALK rearrangement. Patients in both arms must be treated with at least one line of tyrosine kinase inhibitors (TKI). The investigation arm were patients who received immunotherapy at any time during their disease course. The control arm were patients who did not receive immunotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were objective response rate (ORR) and disease control rate (DCR) in the investigation arm. Results: A total of 47 patients met the inclusion criteria: 27 patients received immunotherapy after or before TKI failure, while 20 patients did not receive immunotherapy. Baseline characteristics were similar in both groups. The average age at diagnosis was 65 years and 40% were males. 68% of patients were at stage IV at the time of diagnosis, 43% were never smokers, and 40% had brain metastases. EGFR mutations accounted for 76.6% of alterations, while ALK rearrangement was demonstrated in 17%, MET and BRAF mutations in 4.3% and 2.1% respectively. Among 27 patients in the immunotherapy group, 3 received chemotherapy simultaneously, 11 patients had received prior chemotherapy, while 13 patients were chemotherapy naive. Complete response was achieved in one case. The ORR was 22.2% and DCR was 37%. Targeted therapy was re-introduced in 9 patients after discontinuation of immunotherapy, of whom 3 responded. The median OS was 44 months (95%CI 28.9-59.4) in immunotherapy group versus 35.7 months (95% CI 23.9-47.4) in control group (P-value 0.34). Conclusions: Immunotherapy, as single agent or in combination with chemotherapy, is associated with better OS trend in patients with advanced NSCLC who harbor activation mutations and failed TKI. This effect was not statistically significant. The prospective data in this population is also limited and controversial. More trials are warranted to evaluate the efficacy of immunotherapy in this group.

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