Pooled analysis of clinical outcome for EGFR TKI‐treated patients with EGFR mutation‐positive NSCLC

Abstract

Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n = 731), 54 gefitinib studies (n = 1802) and 20 chemotherapy studies (n = 984) provided median PFS values for each treatment. The pooled median PFS was: 12.4 months (95% accuracy intervals [AI] 11.6–13.4) for erlotinib-treated patients; 9.4 months (95% AI 9.0–9.8) for gefitinib-treated patients; and 5.6 months (95% AI 5.3–6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P = 0.000 and P = 0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy.

Targeted Therapy for Non-Small Cell Lung Cancer

“…[50][51][52] The lack of OS benefit has been ascribed to crossover from the chemotherapy arm to an appropriate TKI, within or outside of the clinical trial. 47,53,54 Despite the lack of OS benefit, TKIs have remained the preferred first-line treatment option for EGFR-mutated NSCLC patients due to the ease of an oral therapy, the higher response rate, and an improved quality of life (QOL). 47,55,56…”

Cucurbitacin E inhibits the Yes‑associated protein signaling pathway and suppresses brain metastasis of human non‑small cell lung cancer in a murine model

“…Treatment options for those patients whose tumors lack targetable mutations remain quite limited. For example, erlotinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), is an effective target therapy for brain metastatic lung adenocarcinoma harboring EGFR exon 19 deletion or exon 21 L858R mutations (5)(6)(7)(8). Anaplastic lymphoma kinase (ALK) inhibitors including ceritinib and alectinib have better response rates than conventional chemotherapy for brain metastatic NSCLC patients with ALK-rearrangement mutation (9,10).…”

Prospective exosome‐focused translational research for afatinib study of non‐small cell lung cancer patients expressing EGFR (EXTRA study)

“…Patients with EGFR ‐mutated advanced NSCLC demonstrate 9–11 months of progression‐free survival (PFS) with first‐generation EGFR‐tyrosine kinase inhibitors (TKIs) . Recently, two important trials using second‐generation EGFR‐TKIs reported > 12 months of PFS.…”

“…1,2 Patients with EGFR-mutated advanced NSCLC demonstrate 9-11 months of progression-free survival (PFS) with first-generation EGFR-tyrosine kinase inhibitors (TKIs). 3 Recently, two important trials using second-generation EGFR-TKIs reported > 12 months of PFS. It is important to note that the Kaplan-Meier curve deviates after 12 months, resulting in a 20% PFS rate after two years with second-generation EGFR-TKIs.…”