Defining the Role of Tyrosine Kinase Inhibitors in Early Stage Non-Small Cell Lung Cancer

Abstract

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.

The Unique Spatial-Temporal Treatment Failure Patterns of Adjuvant Gefitinib Therapy: A Post Hoc Analysis of the ADJUVANT Trial (CTONG 1104)

“…Previous studies of adjuvant EGFR-TKI therapy in NSCLC were conducted in either unselected or small patient groups. 11,12,16 The aim of this post hoc analysis was to compare spatial temporal recurrence patterns between adjuvant gefitinib and VP chemotherapy. It is generally recognized that recurrence rates of resected early-stage NSCLC range from 30% to 75% and result in poor postoperative survival.…”

Prognostic factors for long term survival in patients with advanced non-small cell lung cancer

“…Lung cancer is nowadays a global threat, since it is estimated that 6.94% of men and women born today will be diagnosed with lung cancer at some time in their lives (1). Indeed it is estimated that 2.86% of males and 2.24% of females will be diagnosed with cancer between 50−70 years (2,3).…”

Adjuvant Epithelial Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer

“…The NCTO 1746 251 trial is comparing adjuvant afatinib 40 mg for 3 months vs 3 years for patients with resected stage IA to IIIB NSCLC with EGFR mutations. 10,11 The RTOG 1210/Alliance 31101 is analyzing adjuvant TKI therapy after chemoradiation in patients with EGFR mutation-sensitive cancers. 11 A Chinese trial (C-TONG 1104) is comparing adjuvant TKI agents after resection of stage II to IIIA (N 1 or N 2 ) cancers with EGFR-sensitive mutations.…”