Osimertinib readministration for central nervous system metastases in non-small cell lung cancer positive for EGFR activating mutations.

Background: Osimertinib shows pronounced efficacy for EGFR mutation-positive non-small cell lung cancer (NSCLC) including associated central nervous system (CNS) metastases. Tumors inevitably develop resistance to the drug, however. Osimertinib is sometimes readministered after completion of standard chemotherapy. To clarify which patients might receive benefit from osimertinib readministration, we have retrospectively assessed its efficacy with a focus on CNS metastases.
Methods: A retrospective analysis of medical records was performed for 21 patients who underwent osimertinib readministration at Kyushu University Hospital between March 2016 and April 2023. CNS metastases were evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST).
Results: Among the 21 enrolled patients, 16 individuals had target lesions on the basis of RECIST. One (6.3%) of these 16 patients achieved a partial response to osimertinib readministration, with the remaining 15 patients showing stable or progressive disease. The median overall progression-free survival (PFS) and median overall survival for all 21 patients were 3.8 and 13.9 months, respectively. The efficacy of osimertinib readministration for CNS metastases was evaluable in eight patients including five individuals with leptomeningeal metastases. The objective response rate for CNS metastases and the improvement rate for leptomeningeal metastases were both 100%. The median PFS with regard to CNS or non-CNS lesions for these eight patients was 24.7 and 10.5 months, respectively.
Conclusions: Osimertinib readministration showed limited efficacy for non-CNS lesions but excellent efficacy for CNS metastases, suggesting that such treatment is an option for EGFR-mutated NSCLC patients with CNS metastases.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:E Iwama received honoraria from Chugai Pharmaceutical, Thermo Fisher Scientific and AstraZeneca. Y Shiraishi received from Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, and Bristol Myers Squibb. K Tanaka received honoraria from Nippon Kayaku, Nippon Boehringer Ingelheim, Chugai Pharmaceutical, and Japan Society for the Promotion of Science. I Okamoto received honoraria and research funding from Chugai Pharmaceutical, AstraZeneca, Daiichi Sankyo, Merck & Co Inc, Takeda Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Taiho Pharmaceutical and Nippon Boehringer Ingelheim. I Okamoto received honoraria from Novartis Pharmaceuticals. The remaining authors declare no conflicts of interest.
(Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)