A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, some patients show intrinsic resistance and an insufficient response to osimertinib. Increased expression of the anexelekto (AXL) protein in tumors is reported to be associated with poor prognosis in patients with several types of cancer. We previously reported the crucial role of the AXL pathway in the intrinsic resistance to EGFR-TKIs in EGFR-mutated NSCLC cells. Moreover, AXL overexpression in EGFR-mutated NSCLC specimens was negatively associated with the therapeutic efficacy of first- and second-generation EGFR-TKIs. However, the relationship between AXL expression in tumors and the therapeutic efficacy of osimertinib is still unclear.
We retrospectively enrolled 30 patients with advanced or relapsed NSCLC with EGFR-activating mutations from four institutions in Japan. All patients were administered osimertinib as the first-line treatment between August 2017 and March 2019.
Twenty-two (73.3%) patients were female; 21 (70.0%) patients had never smoked. The median age of patients was 71.0 years (range, 44–88 years of age). The EGFR-activating mutations were deletion in exon 19 in 16 (53.3%) patients; L858R missense mutation in exon 21 in 12 (40.0%) patients; and other types in 2 (6.6%) patients. High (3+), intermediate (2+), low (1+), and no (0) pre-treatment expression of AXL in tumors was observed in 2 (6.7%), 4 (13.3%), 12 (40.0%), and 12 (40.0%) patients, respectively. The maximal tumor shrinkage rate following osimertinib treatment in the patients with AXL expression scores of 0 and 1+ was higher than that in patients with AXL expression scores of 2+ and 3+ (44.12% vs. 25.93%, p = 0.094).
Pre-treatment AXL expression in tumors may be a promising predictor of osimertinib treatment efficacy in patients with EGFR-mutated NSCLC.
The authors.
Has not received any funding.
T. Yamada: Research grant/Funding (self): Pfizer Inc.; Research grant/Funding (self): Ono Pharmaceutical Co., Ltd; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd; Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd. S. Atagi: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squib; Honoraria (self): Hisamitsu; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (institution): F. Hoffmann-La Roche. K. Takayama: Honoraria (self), Research grant/Funding (self): Chugai-Roche Co.; Research grant/Funding (self): Ono Pharmaceutical Co.; Honoraria (self): AstraZeneca Co.; Honoraria (self): MSD-Merck Co.; Honoraria (self): Eli Lilly Co.; Honoraria (self): Boehringer-Ingelheim Co.; Honoraria (self): Daiichi-Sankyo Co. All other authors have declared no conflicts of interest.