Tuberc Respir Dis.  2014 Jan;76(1):8-14.

Long Term Therapeutic Plan for Patients with Non-Small Cell Lung Cancer Harboring EGFR Mutation

• Jang SH

Abstract

Non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) sensitizing mutations has a distinct disease entity. Patients with this cancer have better prognosis, and frequently achieve long-term survival. EGFR-tyrosine kinase inhibitor (TKI) is the drug of choice for this cancer; but the disease inevitably progresses, after durable response. The tumor is a mixture of EGFR-TKI sensitive clones and resistant clones, regardless of their molecular mechanisms. EGFR-TKI sensitive clones are very susceptible to this drug, but rarely eradicated; so, withdrawal of the drug permits rapid regrowth of drug sensitive clones, possibly causing "disease flare." Re-administration or continuation of EGFR-TKI can effectively suppress the expansion of drug sensitive clones, even when the total tumor volume continuously increases. Chemotherapy can definitely prolong the survival of patients experiencing EGFR-TKI failure. Prospective clinical trials are warranted to compare efficacies of chemotherapeutic agents. A few retrospective studies suggested that a taxane-based regimen may be superior to others. Here, we reviewed therapeutic options and clinical evidence about this unique disease entity.

Keyword

Receptor, Epidermal Growth Factor; Carcinoma, Non-Small Cell Lung; Drug Therapy

MeSH Terms

Carcinoma, Non-Small-Cell Lung*
Clone Cells
Drug Therapy
Humans
Phosphotransferases
Prognosis
Receptor, Epidermal Growth Factor
Tumor Burden
Phosphotransferases
Receptor, Epidermal Growth Factor

Figure

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  Figure 1 National Comprehensive Cancer Network (NCCN) practice guideline for epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer16. TKI: tyrosine kinase inhibitor; RT, radiotherapy.

• 

  Figure 2 Schematic tumor volume-time curve according to on-and-off of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). The tumor volume is the sum of EGFR-TKI sensitive clones and resistant clones, regardless of baseline molecular mechanisms. The tumor volume of EGFR-TKI sensitive clones rapidly shrinks with EGFR-TKI administration, but the tumor volume of EGFR-TKI resistant clones steadily increases, despite the treatment. The total tumor volume initially reaches the level of partial response (PR), but re-increases, and after a certain period, eventually progresses (progressive disease [PD]), because of expanding EGFR-TKI resistant clones. Withdrawing EGFR-TKI induces regrowth of EGFR-TKI sensitive clones, possibly causing disease flare. If EGFR-TKI is re-administered, the tumor volume can be stabilized (decreasing stable disease [SD] or PR). However, the progression free survival would be shorter than that of the initial treatment21.

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