1186TiP EPONA, efficacy of osimertinib with platinum and pemetrexed in EGFR mutant non-small cell lung cancer patients bearing CNS metastasis, and have systemic progression but stable intracranial disease on OsimertiNib resistAnce (TORG 1938)

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. 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. jRCTs071200029. Thoracic Oncology Research Group (TORG). AstraZeneca K.K.