100TiP - Phase II study of aumolertinib combined with local radiation therapy for EGFR mutated stage IV NSCLC patients with oligometastasis

Background

Aumolertinib, a 3^rd-generation EGFR-TKI, has demonstrated significant efficacy and good safety profile in NSCLC patients with EGFR-sensitive mutations. Although 3^rd-generation EGFR-TKI has revealed higher efficacy, acquired resistance is a major factor limiting long-term survival. Previous studies have shown that the majority of progression pattern was primary lesion rather than appearance of new metastases in patients treated with EGFR-TKI, and possibly reasons are tumor heterogeneity and the emergence of resistance genes. Local radiotherapy plays an important role in the treatment of oligometastatic patients. However, there is still a lack of prospective clinical data on the combination of local radiotherapy and aumolertinib targeted therapy for advanced oligometastatic NSCLC with EGFR mutations.

Trial design

Approximately 60 stage IV EGFR-mutated oligometastatic NSCLC patients will be enrolled in this study. After 8 weeks of induction therapy with aumolertinib(110mg/day), patients will be randomly divided into two groups. The first group will continue to receive aumolertinib monotherapy, and the second group of patients will be assigned to receive intensity-modulated radiotherapy and then continue to receive aumolertinib. All the patients are permitted to continue treatment until unacceptable toxicity or disease progression. The primary endpoint is PFS.The innovation of this project is that the advantage population of combining aumolertinib with local radiotherapy can be screened. Secondly, previous studies have combined local treatment after disease progression, but the accumulation of malignant clones at this time may increase the risk of progression and subsequent metastasis. The early addition of local radiotherapy is expected to reduce the occurrence of this risk. However, combination radiation therapy may increase the damage to the surrounding normal tissue if the tumor is large at initial diagnosis. This study aims to evaluate whether the intensity-modulated radiotherapy has good synergistic effect when the lesions have a response to aumolertinib, and whether the combined treatment can delay the time to progression (TTP) and OS or not.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.