. Step 13 of 41
Clinical Stem 3
A patient with right upper lobe adenocarcinoma progressing on biomarker-directed therapy

Answer C
Significant clinical or radiographic response to biomarker-driven therapy is seen initially in many patients with EGFR mutations or ALK rearrangements, but disease commonly progresses as a result of acquired resistance against EGFR and ALK inhibitors.

In patients with documented prior actionable genetic alterations in whom disease has progressed during therapy, retesting should be done exclusively on re-biopsy specimens of a progressing lesion; specifically the lesion that had become clinically relevant. Clinicians should communicate this information with their pathologist to ensure that requests for testing on patients with prior history of biopsy are made only for the most recently obtained specimen.

This patient's imaging studies reveal probable disease progression. The benefits of potentially improved outcomes by re-biopsy should be balanced against the risks associated with the use of invasive procedures for tissue acquisition. The location of the tumor and the level of risk involved in the procedure are relevant to deciding whether repeat biopsy is recommended.

For this patient, progression of disease was likely in both the right interlobar node and the primary tumor, but is most obvious in the primary tumor. The primary lesion is therefore the preferred site for rebiopsy.

About 50% of resistant tumors show the T790M mutation, while 5% show MET overexpression and PIK3CA mutations. Transformation into small cell lung cancer occurs in about 15% of tumors. Investigational targeted treatments against T790M mutations, MET- and PIK3CA are currently available in clinical trials

While rebiopsy may allow detection of resistance mechanisms and alter therapy, indications for rebiopsy depend on treatment setting and availability of clinical trials and other cancer-related research.

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References:
  1. Carter CA, Giaccone G. Treatment of nonsmall cell lung cancer: overcoming the resistance to epidermal growth factor receptor inhibitors. Curr Opin Oncol. 2012;24:123?129.
  2. Eberhard DA, Giaccone G, Johnson BE. Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. J Clin Oncol 2008; 26: 983?94.
  3. Thunnissen E, Kerr KM, Herth FJ, et al. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group. Lung Cancer 2012; 76: 1-18.
  4. Schumann S, Hetzel J, Babiak A et al. Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions. J Thorac Cardiovasc Surg 2010;140:417-421.
  5. Griff S, Ammenwerth W, Schonfeld et al. Morphometrical analysis of transbronchial cryobiopsies. Diagn Pathol. 2011 Jun 16;6:53.
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