Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With EGFR-Sensitizing Variants Assessed by Circulating Tumor DNA Testing

Abstract

The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice. OBJECTIVE To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (EGFR)-sensitizing variants assessed by circulating tumor DNA (ctDNA). DESIGN, SETTING, AND PARTICIPANTS The Efficiency of Icotinib in Plasma ctDNA EGFR Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma EGFR-sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA EGFR variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with EGFR variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021.INTERVENTIONS Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent. MAIN OUTCOMES AND MEASURESThe primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms. RESULTSOf 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable.CONCLUSIONS AND RELEVANCE This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based EGFR genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration.

Liquid Biopsy in NSCLC: An Investigation with Multiple Clinical Implications

“…After a median follow-up of 12 months, median PFS was 10 months and median OS was not reached. Similar results have been described in a Phase 2 study with Icotinib [ 54 ], confirming the possibility to rely on liquid biopsy to start treatment with EGFR TKIs, even if a pathological diagnosis is unavailable.…”

Comparative efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced driver-gene negative non-small cell lung cancer: A systematic review and network meta-analysis

“…In colon cancer, it can guide adjuvant therapy, while in lung cancer, it can assist in anti-EGFR therapy. Moreover, ctDNA can provide insights into the mechanisms of drug resistance in rectal cancer [ [81] , [82] , [83] , [84] , [85] , [86] ]. However, the routine clinical use of ctDNA is presently limited due to technological constraints in detection and tumor staging.…”

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

“…It can monitor treatment response and predict real-time prognoses by assisting in early cancer diagnosis and recognizing small residual diseases or recurrence rates ( 176 ). Analyzing ctDNA from patients with metastatic colorectal cancer allows for monitoring of the disease’s temporal heterogeneity and individualized treatment, as more and more studies are showing ( 172 , 174 ). Wyatt et al.…”