Abstract 1186TiP
Background
Central nervous system (CNS) protection is a crucial strategy for the long-term survival of patients (pts) with cancer. Currently, pts with epidermal growth factor receptor (EGFR)-mutant (mt) non-small cell lung cancer (NSCLC) have expected longer survival after treatment with EGFR-TKIs. Osimertinib is a current standard of care (SOC) for EGFR-mt NSCLC and has been clinically shown to control the CNS progression. The current SOC involves switching to platinum doublet chemotherapy and discontinuing osimertinib if the CNS is under control after progression at other sites. However, based on tumor heterogeneity, subsequent chemotherapy does not always maintain control of CNS lesions. The Phase II trial EPONA (jRCTs: 071200029) is investigating secondary osimertinib chemoprevention in the CNS when administered in combination with platinum doublet chemotherapy in pts with progression disease (PD) outside of the CNS lesions.
Trial design
EPONA is a randomized controlled, multicenter, open-label, phase II trial in pts with brain metastatic EGFR-mt NSCLC previously treated with osimertinib. This trial evaluates the efficacy of platinum and pemetrexed (pem) treatment followed by pem maintenance with or without continuation of osimertinib for secondary CNS prevention. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, response rate, time to CNS progression, time to whole-brain irradiation, and safety. Key eligibility criteria are as follows: ECOG PS, 0–2; and non-squamous histology. Pts are required to succeed for at least 32 weeks. Approximately 90 pts will be randomized across treatment arms, stratified by previous treatment history for CNS metastases, EGFR mt subtypes, and osimertinib naïve vs. T790M. Pts in arm A (SOC arm) will receive either carboplatin or cisplatin/pem, followed by pem maintenance until PD or unacceptable toxicity. Pts in arm B (study arm) will receive platinum/pem + osimertinib followed by maintenance pem + osimertinib. These results are expected by 2025. This study is funding by AstraZeneca.
Clinical trial identification
jRCTs071200029.
Editorial acknowledgement
Legal entity responsible for the study
Thoracic Oncology Research Group (TORG).
Funding
AstraZeneca K.K.
Disclosure
Y. Okuma: Financial Interests, Personal, Invited Speaker: AstraZeneca, K. K., Nippon Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Eli Lilly K. K., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie, G.K., Chugai Co., Ltd. S. Nomura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, KyowaHakko Bio; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. K. Ninomiya: Financial Interests, Personal, Invited Speaker: AstraZeneca K. K., Nippon Boehringer Ingelheim, Kyowa Kirin, Lilly Japan, Chugai Pharmaceutical Co., Ltd., Nippon Kayaku, Taiho Pharmaceutical Co., Ltd., MSD K. K., Ono Pharmaceutical Co., Ltd., Novartis Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Co., Ltd., Bristol Myers Squibb. H. Yamaguchi: Financial Interests, Personal, Invited Speaker: AstraZeneca K. K., Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Novartis Pharma, Taiho Pharmaceutical, Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Sponsor/Funding: Nippon Boehringer Ingelheim Co., Ltd. S. Murakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan, Bristol Myers Squibb, Taiho Pharmaceutical, Boehringer Ingelheim, Novartis, Merck BioPharma; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, Janssen Pharmaceutical, MSD, Sanofi. Y. Kogure: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Boehringer Ingelheim, Ono Pharmaceutical; Financial Interests, Institutional, Invited Speaker: MSD, Taiho Pharmaceutical. D. Harada: Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd. , Eli Lilly and Company, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, Towa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., MSD K. K. K. Okishio: Financial Interests, Personal, Invited Speaker: Astra Zeneca, Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb. H. Okamoto: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Chugai, Taiho Pharmaceutical Co., Ltd., Astellas, Eli Lilly, Merck BioPharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Chugai, Boehringer Ingelhei, Bristol Myers Squibb, Novartis, Kyorin. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., Illumina, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Johnson and Johnson, D3bio; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Thermo Fischer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Guardant Health, Preferred Network; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Prefered Network.