EGFR–TKI tumour response predicts NSCLC survival
medwireNews: A partial or complete response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is significantly associated with survival in patients with non-small-cell lung cancer (NSCLC), research suggests.
Of 68 patients with EGFR mutation-positive NSCLC who were treated with TKIs, six patients achieved a complete response, 42 achieved a partial response and 14 had stable disease, giving an overall response rate of 71% and a control rate of 91%, report Isamu Okamoto (Kyushu University Hospital, Fukuoka, Japan) and co-authors.
Progression-free survival (PFS) was significantly longer in patients with a tumour response than those with stable disease, at a median of 15.9 versus 8.5 months. A similar benefit was found for overall survival (OS), at a median of 44.4 versus 12.2 months.
Multivariate analysis adjusting for age, gender, specific EGFR mutation, smoking history, receipt of erlotinib or gefitinib and tumour response confirmed these results, the team writes in the Journal of Thoracic Oncology.
PFS was significantly predicted by a partial or complete tumour response to EGFR–TKI therapy (adjusted hazard ratio [HR]=0.33) and a favourable performance status (adjusted HR=0.25), while OS was significantly predicted by tumour response (adjusted HR=0.29), performance status (adjusted HR=0.18) and female gender (adjusted HR=0.22).
The researchers also looked at the relationship between maximal tumour shrinkage achieved and survival outcomes but did not find a significant correlation. Nor was there any significant association between the median time to response to EGFR–TKI therapy and PFS.
Okamoto et al note that these patterns are in contrast to those seen in many oncogene-addicted tumours which have a quick response to molecularly targeted drugs.
Recognising that tumours with EGFR mutations often develop TKI resistance by acquiring further mutations, the researchers hypothesise that “time to acquired resistance (disease progression) after initiation of EGFR-TKI therapy is defined by the duration of EGFR-TKI exposure, regardless of the time to onset of tumor response or the extent of tumor shrinkage.”
They therefore conclude that “response… may represent the optimal surrogate for survival among EGFR mutation–positive NSCLC patients treated with EGFR-TKIs.”
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By Lynda Williams, Senior medwireNews Reporter