Pattern of Recurrence Analysis in Metastatic EGFR-Mutant NSCLC Treated with Osimertinib: Implications for Consolidative Stereotactic Body Radiation Therapy
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Published on: November 22, 2021
Tiantian Guo1, Jianjiao Ni1, Xi Yang1
1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Purpose:
Despite the impressive response rate to osimertinib, acquired resistance remains an obstacle to achieving long-term tumor control in metastatic epidermal growth factor receptor-mutant non-small cell lung cancer. Stereotactic body radiation therapy (SBRT) plays a growing role in the management of oligometastatic disease. We investigated the patterns of residual disease and progression on osimertinib, as well as the predictors of candidates for consolidative SBRT.
Methods And Materials:
The serial scans of patients with metastatic epidermal growth factor receptor-mutant non-small cell lung cancer treated with osimertinib were retrospectively reviewed. Disease progression in residual sites, new sites, and both residual and new sites were classified as residual-site recurrence (RR), new-site recurrence (NR), and combined RR and NR (RNR), respectively. Logistic regression analysis was performed to identify predictors of candidates for consolidative SBRT.
Results:
Ninety-seven patients were enrolled. The median time to maximal osimertinib response was 2.6 months. Twenty-six patients (26.8%) with oligoresidual disease were identified as candidates for consolidative SBRT at time of maximal response. Stage T1-2 before initiation of osimertinib (P = .046) was the independent predictor of consolidative SBRT eligibility. During a median follow-up of 10.9 months, disease progression was documented in 50 (51.5%) patients, and 70% of them experienced oligoprogression. Twenty-five (50%) patients developed disease progression in originally involved sites, 11 (22%) had new metastases, and 14 (28%) experienced disease progression in both original and new metastatic sites. Forty-six patients had progressive disease after experiencing initial stable disease or objective response to osimertinib. RR occurred in 20 (43.5%) of these patients, NR in 14 (30.4%), and RNR in 12 (26.1%). Notably, within the subgroup of patients eligible for consolidative SBRT, RR was observed in 6 (54.5%) patients, RNR in 3 (27.3%), and NR in 2 (18.2%).
Conclusions:
The majority of progressive disease on osimertinib was within residual lesions in initially involved sites. Consolidative SBRT may prolong time to progression in a selected subgroup of patients, which merits further investigation.
Insights
Acquired resistance to osimertinib in EGFR-mutant lung cancer is common. Consolidative stereotactic body radiation therapy (SBRT) may benefit selected patients with oligoprogression, particularly those with residual-site recurrence.
Area of Science:
- Oncology
- Radiation Oncology
- Medical Physics
Background:
- Acquired resistance to osimertinib is a significant challenge in managing metastatic EGFR-mutant non-small cell lung cancer (NSCLC).
- Stereotactic body radiation therapy (SBRT) is increasingly utilized for oligometastatic disease.
- Understanding patterns of progression and identifying candidates for consolidative SBRT is crucial.
Purpose of the Study:
- To investigate patterns of residual disease and progression in patients with metastatic EGFR-mutant NSCLC treated with osimertinib.
- To identify predictors for patients eligible for consolidative SBRT.
- To evaluate the role of SBRT in managing oligoprogression.
Main Methods:
- Retrospective review of serial scans from 97 patients with metastatic EGFR-mutant NSCLC treated with osimertinib.
- Classification of disease progression into residual-site recurrence (RR), new-site recurrence (NR), and combined RR and NR (RNR).
- Logistic regression analysis to identify predictors of SBRT eligibility.
Main Results:
- 26.8% of patients were identified as candidates for consolidative SBRT.
- Stage T1-2 disease before osimertinib was an independent predictor of SBRT eligibility.
- In patients eligible for SBRT, RR was the most common pattern of progression (54.5%).
- Overall, 51.5% of patients experienced disease progression, with 70% showing oligoprogression.
Conclusions:
- The majority of progressive disease on osimertinib occurs within residual lesions at initially involved sites.
- Consolidative SBRT shows potential to prolong time to progression in a select group of patients.
- Further investigation is warranted to confirm the benefit of SBRT in this patient subgroup.
