Continuing gefitinib therapy plus localized therapy may provide a benefit among patients with asymptomatic slow progression or oligometastatic EGFR-mutant non-small cell lung cancer (NSCLC) post-progression, according to a study published in Lung Cancer.1
Targeted therapies such as EGFR tyrosine kinase inhibitors (TKI) have improved survival in NSCLC, but the development of drug resistance is a common challenge. Recent studies have shown that continuing EGFR-TKIs with local treatment, such as radiotherapy or radiosurgery, may be beneficial even after the development of drug resistance — but there is a paucity of evidence and guidance on proper use within this treatment approach.
For this phase 2 study, researchers enrolled 50 patients with EGFR-mutant NSCLC who experienced asymptomatic disease progression while on gefitinib therapy; patients continued treatment until symptomatic progression or at the investigators’ discretion. Eligible patients had previously achieved complete response or partial response for more than 4 months or stable disease for more than 6 months while receiving gefitinib as a first- or second-line therapy. Tumor assessments were done every 8 weeks via computed tomography (CT).
The primary outcome was progression-free survival-2 (PFS2), which was defined as the time from the first gefitinib dose to off-gefitinib progression, and secondary outcomes included PFS1 (time from first gefitinib dose to RECIST 1.1 progression), PFS2-PFS1, overall survival (OS), and safety. Due to poor enrollment, the study was prematurely terminated.
Results of 40 evaluable patients showed that the median PFS2 was 27.7 months (95% CI, 21.6-33.9), and the median PFS2-PFS1 was 5.1 months (95% CI, 2.5-7.8). Twelve patients continued gefitinib therapy for a median of 14 months post-RECIST 1.1 progression. The median OS was not evaluable.
New lesions or slow progression of preexisting lesions were managed with local treatment. Once the characteristics of progression at the time of study enrollment were considered, median PFS2-PFS1 was 1.8 months among patients with pleural metastasis or pleural effusion versus 7.1 months among patients with other types of progression (P = .005).
The authors concluded that “in patients with EGFR-mutant NSCLC who experience progression, it is beneficial to maintain gefitinib treatment with local treatment such as radiotherapy until symptomatic progression. However, in patients with pleural metastasis or effusion, continuation of gefitinib beyond progression should be carefully determined on a case-by-case basis.”
- Lim SW, Park S, Kim Y, et al. Continuation of gefitinib beyond progression in patients with EGFR mutation-positive non-small-cell lung cancer: a phase II single-arm trial [published online August 3, 2018]. Lung Cancer. doi: 10.1016/j.lungcan.2018.08.003.