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Randomized Controlled Trial
. 2023 Jun 8;115(6):742-748.
doi: 10.1093/jnci/djac015.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer

Xiao-Shan Wang  1 , Yi-Feng Bai  1 , Vivek Verma  2 , Rui-Lian Yu  1 , Wei Tian  1 , Rui Ao  1 , Ying Deng  1 , Xue-Qiang Zhu  1 , Hao Liu  1 , Hai-Xia Pan  1 , Lan Yang  1 , Han-Song Bai  3 , Xing Luo  3 , Yan Guo  3 , Ming-Xiu Zhou  3 , Yue-Mei Sun  4 , Zi-Can Zhang  4 , Si-Min Li  3   5 , Xue Cheng  3 , Bang-Xian Tan  3 , Liang-Fu Han  6 , Ying-Yi Liu  7 , Kai Zhang  8 , Fan-Xin Zeng  9 , Lin Jia  10 , Xin-Bao Hao  11 , You-Yu Wang  1 , Gang Feng  1 , Ke Xie  1 , You Lu  12 , Ming Zeng  1
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Randomized Controlled Trial

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer

Xiao-Shan Wang et al. J Natl Cancer Inst. .

Erratum in

Expression of concern in

Abstract

Background: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.

Methods: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.

Results: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.

Conclusions: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

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Figures

Figure 1.
Figure 1.
CONSORT diagram for the trial. RT = radiation therapy; TKI = tyrosine kinase inhibitor.
Figure 2.
Figure 2.
Kaplan-Meier curves illustrating progression-free survival between arms. RT = radiation therapy; TKI = tyrosine kinase inhibitor.
Figure 3.
Figure 3.
Kaplan-Meier curves illustrating overall survival between arms. RT = radiation therapy; TKI = tyrosine kinase inhibitor.
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Comment in

References

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