Mixed response to osimertinib and the beneficial effects of additional local therapy

Abstract

Background: Although non-small cell lung cancers (NSCLCs) harboring EGFR mutations initially respond well to EGFR-tyrosine kinase inhibitors (TKIs), they typically progress after approximately one year. The EGFR T790M mutation is the most common resistance mechanism. NSCLCs with T790M respond well to osimertinib; however, the heterogeneity of NSCLCs may limit the efficacy. Some patients exhibit a mixed response (MR), in which some lesions shrink and others progress, but little is known of the incidence and characteristics of such a response. We sought to determine the frequency and clinical course in MR patients. Methods: We retrospectively reviewed the records of patients who had received osimertinib for NSCLC with EGFR T790M. Results: Between April and December 2016, 48 patients were administered osimertinib. Seven patients (15%) exhibited one of two MR types: (i) progressive lesions that did not include the re-biopsy site (5 patients), and (ii) progressive lesions that included the re-biopsy site (2 patients). The most frequent progressive sites were liver and lung metastases (4 patients). Three patients continued osimertinib following an MR, one of whom had received local therapy for liver metastasis and achieved disease control on osimertinib for an additional four months. Conclusion: An MR was detected in 15% of NSCLC patients with T790M. This finding suggests that several different resistance mechanisms are active within a single patient who develops resistance to EGFR-TKIs. Osimertinib is basically effective for tumors that acquire resistance to EGFR-TKIs as a result of T790M mutation. Therefore, additional local therapy may be beneficial for patients who develop an MR to osimertinib.