Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status

Wenzhao Zhong, Xuening Yang, Honghong Yan, Xuchao Zhang, Jian Su, Zhihong Chen, Riqiang Liao, Qiang Nie, Song Dong, Qing Zhou, Jinji Yang, Haiyan Tu, Yi-Long Wu, Wenzhao Zhong, Xuening Yang, Honghong Yan, Xuchao Zhang, Jian Su, Zhihong Chen, Riqiang Liao, Qiang Nie, Song Dong, Qing Zhou, Jinji Yang, Haiyan Tu, Yi-Long Wu

Abstract

Background: Neoadjuvant erlotinib and customized adjuvant therapy are appealing but controversial. The purpose of this study was to evaluate the role of biomarker-guided neoadjuvant treatment strategy in patients with IIIA-N2 non-small cell lung cancer (NSCLC) stratified by epidermal growth factor receptor (EGFR) mutation status.

Findings: Patients with resectable histologically documented stage IIIA-N2 NSCLC were assigned to a neoadjuvant erlotinib arm or a gemcitabine/carboplatin (GC) arm based on EGFR mutation status. The primary endpoint was response rate (RR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Twenty-four patients with IIIA-N2 NSCLC were enrolled in the trial from January 2008 until May 2011. The overall response rate was 41.7% and the PFS and OS were 7.9 and 23.2 months, respectively, in overall population. The RR was 58.3% (7/12) for the erlotinib arm with mutant EGFR and 25.0% (3/12) for the GC arm with wild type EGFR (P = 0.18). Median PFS was 6.9 months versus 9.0 months, respectively (P = 0.071). Median OS was 14.5 months for the erlotinib arm and 28.1 months for the GC arm (P = 0.201). No unexpected toxicities were observed.

Conclusions: The primary endpoint was met and biomarker-guided neoadjuvant treatment strategy in patients with IIIA-N2 NSCLC is feasible. Erlotinib alone in neoadjuvant setting of EGFR mutant population showed an improved response but without survival benefits.

Trial registration: ClinicalTrials.gov NCT00600587 https://www.clinicaltrials.gov/ct2/show/NCT00600587?term=NCT00600587&rank=1.

Figures

Fig. 1
Fig. 1
Waterfall plot of response to neoadjuvant treatment. Abbreviations: GC, gemcitabine/carboplatin; E, erlotinib. Note: The response rate of one case in the GC arm was not available
Fig. 2
Fig. 2
PFS and OS. a PFS and OS for the total population; b PFS comparison between two arms; c OS comparison between two arms; d PFS for the resection patients; e OS for the resection patients; f The 2nd PFS. Abbreviations: GC, gemcitabine/carboplatin; PFS, progression-free survival; OS, overall survival
Fig. 3
Fig. 3
Plasma L858R abundance in the neoadjuvant TKI setting. Abbreviations: PR, partial response; SD, stable disease; TKI, tyrosine kinase inhibitor. One week after the R0 resection, the abundance of plasma L858R decreased significantly, but it rebounded soon after progression. However, the PR in the first- and second-line TKI therapy did not decrease the level of plasma L858R for one case
Fig. 4
Fig. 4
Study design of the CTONG 1103 (EMERGING). Abbreviations: NSCLC, non-small cell lung cancer; EBUS, endobronchial ultrasound; EGFR, epidermal growth factor receptor; ECOG, Eastern Cooperative Oncology Group; PD, progressive disease; ORR, object response rate, CR, complete response; PFS, progression-free survival; OS, overall survival; QOL, quality of life
Fig. 5
Fig. 5
Flow chart. Abbreviations: NSCLC, non-small cell lung cancer; EGFR, epidermal growth factor receptor; E, erlotinib; GC, gemcitabine/carboplatin; PR, partial response; SD, stable disease; PD, progressive disease; NA, not available; PORT: postoperative radiotherapy; Nad,neoadjuvant; MT, mutant type; WT, wild type

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