Efficiency integrated chemotherapy with EGFR receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer and an activating EGFR gene mutation.

Abstract

The EGFR gene mutation occurs in 15% of patients with NSCLC. Tumors with such a molecular genetic profile are characterized by high sensitivity to therapy with EGFR tyrosine kinase inhibitors. However, the majority of EGFRm+ patients develop resistance to 1-2 generation TKI therapy after 9-13 months. In our study, we considered an integrated regimen combined use chemotherapy and targeted therapy as a possible way to overcome acquired tumor resistance to TKIs of 1–2 generations. The study included patients with IIIB / IV stages of NSCLC with activating EGFR mutations.  Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The median PFS was 20.- months (16.0-23.9 months, CI 95%).  One -year progression-free survival (PFS) in patients who completed the chemotherapy stage was 79,6 %, two-year PFS - 38,9%. Brain metastases among patients with a progression of the disease were observed in 12 people (28.6%). The data obtained confirm the promise of using integrated chemotherapy with TKIs as a way to overcome the development of acquired resistance to TKIs of 1–2 generations.