Clinical Outcomes of Different Generations of EGFR Tyrosine Kinase Inhibitors in Advanced Lung Adenosquamous Carcinoma.

Abstract

The role of targeted therapy in patients with lung adenosquamous carcinoma (ASC) has been controversial and it was unclear whether a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could improve outcomes. This study was designed to evaluate the efficacy of different generations of EGFR TKI therapy in ASC patients with sensitive EGFR mutations. Patients with non-small cell lung cancer (NSCLC) diagnosed at the Shanghai Chest Hospital between January 2010 and December 2016 were retrospectively reviewed. A total of 10,037 NSCLC patients tested for EGFR mutations were screened, with primary ASC accounting for 1.4% (139/10,037). Positive EGFR mutations were found in 51.1% (71/139) of ASC patients, including 67 sensitive mutations (19del or 21L858R) and four uncommon mutations (19del + 20T790M, 21L858R + 20T790M, 19L747P + 20Q787Q, and 21L861Q). Sensitive EGFR mutations occurred more frequently in younger (62.0 vs 65.0, p = 0.010), non-smoking (83.6% vs 57.8%, p = 0.002) women (56.7% vs 34.4%, p = 0.014). Among the 36 ASC patients with eligible survival data for the first-generation TKIs, the median progression-free survival (PFS) was 9.3months (95% CI 6.7-11.9), which was rather similar to the data of adenocarcinoma (9.3 vs 11.4months, p = 0.294) in our institution as opposed to squamous cell carcinoma (9.3 vs 4.9months, p < 0.001). The objective response rate (ORR) was 37.9% (11/29), and the disease control rate (DCR) was 86.2% (25/29). After progression on the initial EGFR TKIs, 42.1% of the cases (8/19) had an EGFR T790M mutation detected. A median PFS of 10.2months (95% CI 5.8-14.5, n = 8) was achieved with treatment using the third-generation TKI. The ORR and DCR were 37.5% (3/8) and 100% (8/8), respectively. The median overall survival reached 38.3months (95% CI 13.7-62.9). Targeted therapy showed remarkable efficacy in ASC patients harboring sensitive EGFR mutations, comparable to adenocarcinoma. The application of the third-generation TKI provided an option to prolong survival.