Rebiopsy of Histological Samples in Pretreated Non-small Cell Lung Cancer: Comparison Among Rebiopsy Procedures

Abstract

Abstract. Aim Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancers, and the majority are already unresectable and metastatic upon their initial diagnosis. Cytotoxic chemotherapies such as platinum-based regimens were once the primary therapeutic option for metastatic NSCLC, but their advancement has reached a plateau. Molecular-targeted therapies have been recently developed, and they have provided a remarkable benefit to patients harboring specific genetic alterations such as epidermal growth factor receptor (EGFR) gene mutations or anaplastic lymphoma kinase (ALK) gene fusions (1-3). Efficacies of up-front EGFR-and ALK-tyrosine kinase inhibitors (TKIs) have been established for patients harboring these genetic alterations in prospective randomized phase III trials comparing platinum doublets, and the median progression-free survivals (PFSs) are approximately 12 months (4, 5). Despite an initial dramatic response, most patients receiving these TKIs finally acquire resistance.Several acquired resistant mechanisms to EGFR-TKIs have been identified (6-9), and the "gatekeeper" EGFR mutation, a threonine-to-methionine substitution at amino acid position 790 in exon 20 (T790M), is the most common mechanism and accounts for more than half of acquired resistance to EGFR-TKIs (10). Therefore, it is clinically important to develop more effective therapies for patients with T790M. Indeed, third-generation EGFR-TKIs have been developed, and have demonstrated their remarkable efficacies for patients with T790M (11, 12). Because a thirdgeneration EGFR-TKI is indicated only in cases where histological samples reveal T790M, histological rebiopsy to confirm T790M status becomes essential in clinical practice for patients after acquired resistance to EGFR-TKIs.On the other hand, current advancement of immunotherapies is evolving. Among them, anti-programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) antibodies have demonstrated their notable efficacies in pretreated NSCLC. Anti-PD-1 antibodies, nivolumab, pembrolizumab and atezolizumab have shown survival benefit compared to docetaxel monotherapy in pretreated patients with NSCLC after failure of platinum doublet chemotherapies in randomized phase III trials (13)(14)(15)(16) (18), and rebiopsied histological samples may be desirable before PD-L1 IHC examinations.Based on the above background, rebiopsy of histological sample is necessary to confirm T790M/PD-L1 status. However, histological rebiopsy is an invasive manner, and tissue availability and procedural feasibility make it more challenging, resulting in limited data focusing on histological rebiopsy. We thus reviewed pretreated NSCLC cases receiving rebiopsy of histological samples at our institutes. Patients and MethodsPatients. We retrospectively screened electronic medical records of patients with NSCLC who had received histological rebiopsies in our institutes (Institute of Biomedical Research and Innovation [IBRI], ...

Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

“…Recently, several reports reflecting the reality in different countries have been published. 8,22,[24][25][26] Most studies reported a high re-biopsy success rate, ranging from 75% to 97%, 6,7,9,11 similar to the results of our study. The rebiopsy complication rate is reported to be 1.3-5.8%, 10,11 which is similar to that of initial lung biopsy.…”

“…However, re‐biopsy is still challenging in real world clinical practice because of its invasiveness and the different medical environments found in different countries. Recently, several reports reflecting the reality in different countries have been published . Most studies reported a high re‐biopsy success rate, ranging from 75% to 97%, similar to the results of our study.…”

“…Several studies have reported high success rates of re-biopsy, ranging from 75% to 97%. [6][7][8][9][10][11] However, re-biopsy is still challenging in real practice because of several hurdles, including tissue availability, procedural feasibility, and limited accessibility to new anti-cancer drugs, which differ in different countries. As limited data is available on the feasibility of re-biopsy and its clinical impact in real-world clinical practice, the aim of this study was to assess successful re-biopsy rates and the factors influencing re-biopsy in Korean real world clinical practice.…”

“…With the development of third generation EGFR‐TKIs, re‐biopsy is even more important in order to identify T790M mutations. Several studies have reported high success rates of re‐biopsy, ranging from 75% to 97% . However, re‐biopsy is still challenging in real practice because of several hurdles, including tissue availability, procedural feasibility, and limited accessibility to new anti‐cancer drugs, which differ in different countries.…”

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

“…In treatment strategies based on recent developments in mutation research in NSCLC, re-biopsy has become essential for investigating the tolerance mechanism of a progressed tumor after the initial TKI therapy [ 15 ]. At present, however, re-biopsy is performed only in selected cases in which disease lesions are easily accessible using conventional methods of biopsy [ 16 , 17 ]. It is not clear whether re-biopsy could be applied as a standard technique in all cases of disease progression after chemotherapy.…”