Erlotinib: How to increase the duration of effective use of tyrosine kinase inhibitors in non-small cell lung cancer with EGFR mutation

Abstract

Tyrosine kinase inhibitors of the first, second and third generations are the main treatment method for non-small cell lung cancer with EGFR mutation. About 60% of patients progressing on a first-generation or second-generation tyrosine kinase inhibitor acquire T790M mutation. An alternative is first-line osimertinib, but second-line treatment options are limited, and therefore it is important to find a strategy that allows to extend the effective treatment of TKI. One of the rational approaches is the use of a combination of a first-generation tyrosine kinase inhibitor with anti-VEGF agents. The available information sources show an increase in the effectiveness of the combined use of erlotinib and antiangiogenic drugs-bevacizumab and ramucirumab. The combination of erlotinib and bevacizumab in several studies of the second — third phase, led to a statistically significant increase in progression-free survival, but did not show a significant increase in overall survival. In the Phase 3 RELAY study, the combination of erlotinib and ramucirumab showed comparable efficacy with the third-generation TKI — osimertinib in the first line, however, overall survival results are not yet available. At the same time, there are more opportunities to choose the secondline mode, taking into account the known frequency of detection of the T790M mutation. The optimal treatment sequence is discussed, with the option of prescribing a combination of erlotinib with bevacizumab or ramucirumab in the first line and osimertinib in the second in the presence of the T790M mutation. In such patients, osimertinib may be prescribed in the second line.