Feasibility of tissue re-biopsy in non-small cell lung cancers resistant to previous epidermal growth factor receptor tyrosine kinase inhibitor therapies

Abstract

BackgroundWhen epidermal growth factor receptor (EGFR) gene mutation-positive non-small cell lung cancer (NSCLC) acquires resistance to the initial tyrosine kinase inhibitor (TKI) treatment, reassessing the tumor DNA by re-biopsy is essential for further treatment selection. However, the process of TKI-sensitive tumor re-progression and whether re-biopsy is possible in all cases of acquired resistance to EGFR-TKI remain unclear.MethodsWe retrospectively analyzed data from 69 consecutive patients with EGFR gene mutation-positive advanced NSCLC who had been treated with EGFR-TKI and exhibited disease relapse after initial disease remission. The relapsing lesions were identified at the time of RECIST-progressive disease (PD) and clinical-PD (when the attending physician judged the patient as clinically relapsing and stopped EGFR-TKI therapy). We determined the potential re-biopsy methods for each relapsing lesion and evaluated their feasibility according to difficulty and invasiveness criteria as follows: category A, accessible by conventional biopsy techniques; category B, difficult (but possible) to biopsy and accessible with invasive methods; and category C, extremely difficult to biopsy or inaccessible without using highly invasive methods, including surgical biopsy.ResultsThe total feasibility rate of re-biopsy (category A or B) was 68% at RECIST-PD and 84% at clinical-PD, and the most common accessible relapsing lesions were primary tumors at RECIST-PD and pleural effusion at clinical-PD. All relapsing lesions at primary sites (categories A and B) were assessed as having the potential for re-biopsy. However, re-biopsy for metastasis was assessed as difficult in a substantial proportion of the study population (42 and 20% category C at RECIST-PD and clinical-PD, respectively).ConclusionsRe-biopsy of relapsing disease is feasible in many cases, although it may present difficulties in cases with, e.g., metastatic relapsing lesions. To facilitate treatment strategies in NSCLC patients with relapse after EGFR-TKI therapy, re-biopsy should be standardized with the use of simpler and more reliable methods.

T790M Correlates with Longer Progression-free Survival in Non-small Cell Lung Carcinomas HarboringEGFRMutations

“…Therefore, the performance of a rebiopsy is important in detecting T970M mutations in those patients. Ideally, rebiopsy should be performed in all such patients; however, it is feasible in only 68-82% of cases (12). It stands to reason to perform the rebiopsy from the site that will provide the higher probability of detecting the T790M mutation.…”

“…This is consistent with the results obtained by Gaut et al (15) who showed that T790M-positive patients on first-line treatment had a significantly longer PFS than T790M-negative patients (12.0 months vs. 9.0 months, p=0.021). In addition, T790M-positive patients have also been reported to have long post-progression survival (5,12).…”

The Validity and Predictive Value of Blood-Based Biomarkers in Prediction of Response in the Treatment of Metastatic Non-Small Cell Lung Cancer: A Systematic Review

“…Besides being performed in case of an inadequate first sample, re-biopsies can be performed to track tumor progression and clonal evolution. Since a re-biopsy does also not always provide sufficient tissue for molecular testing, liquid biopsies (LBs) might help overcome this issue [8][9][10]. LBs provide an alternative way of obtaining genetic information without the need for an invasive procedure, the low patient burden allows for more frequent biopsies to guide treatment decisions.…”

Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer

“…Although genetic testing of tumor tissue is the standard method for mutation profiling of NSCLC, the tumor biopsy is invasive and limited by accessibility. In deed, the feasibility of performing tissue biopsy is low in advanced NSCLC patients who are in metastatic stages (8). Consequently, databases built from tissue based testing may under-represent the mutation profiles of advanced NSCLC patients (9).…”

“…As such, the clinical validation of whether cfDNA sequencing could serve as a non-invasive, alternative approach to tissue biopsy in a larger cohort of patients is needed. However, it has been reported that 20-50% of patients with advanced metastatic NSCLC are not fit for tumor biopsy testing (8,19), thus making a large-scale comparison between matched plasma and tissue samples a challenge, both logistically and ethically. In this study, we performed liquid biopsy on a large cohort of Vietnamese NSCLC patients to examine whether it can accurately represent the mutation profiles previously obtained by direct analysis of tumor derived DNA (7).…”