Second‐line therapy with first‐ or second‐generation tyrosine kinase inhibitors in EGFR‐mutated non‐small cell lung cancer patients with T790M‐negative or unidentified mutation

Abstract

Background T790M mutation causes resistance to tyrosine kinase inhibitors (TKIs) in approximately 49% of patients with epidermal growth receptor‐mutant non‐small cell lung cancer (NSCLC). The cause of resistance in the remaining half of the cases is a minor mutation or unknown. Here, we conducted a retrospective study of epidermal growth receptor‐mutant NSCLC patients with T790M‐negative or an unidentified mutation to appraise the therapeutic response to first‐ or second‐generation tyrosine kinase inhibitors as a second‐line treatment. Methods The study included 39 patients treated in our institution from April 2012 through March 2020 with second‐line tyrosine kinase inhibitors or chemotherapy after completing a first‐line therapy with tyrosine kinase inhibitors. Results The patients were allocated to two groups: chemotherapy (n = 28) and a tyrosine kinase inhibitor (n = 11) groups. The median progression‐free survival (PFS) was 5.4 months in the chemotherapy group and 3.4 months in the tyrosine kinase inhibitor group (p‐value = 0.36), while the median overall survival (OS) was 16.1 months in the chemotherapy group and 12.8 months in the tyrosine kinase inhibitor group (p‐ value = 0.20). This study showed no significant difference in PFS and OS between the chemotherapy and tyrosine kinase inhibitor groups. Conclusions These observations suggest that first‐ and second‐generation tyrosine kinase inhibitors are not recommended for second‐line treatment in epidermal growth factor receptor‐mutated NSCLC patients with T790M‐negative mutation who have received tyrosine kinase inhibitors as first‐line treatment.

Optimizing Patient Outcomes Through Sequential EGFR TKI Treatment in Asian Patients With EGFR Mutation-Positive NSCLC

“… 99 Another real-world study from Japan reviewed medical records between 2012 and 2020 to compare the efficacy of first- or second-generation TKIs with chemotherapy as second-line therapy in patients with T790M-negative NSCLC (n = 39). 100 Median PFS and OS were 5.4 and 16.1 months in the chemotherapy group versus 3.4 and 12.8 months in the TKI group, respectively. 100 Similarly, in a study comparing the efficacy of anlotinib versus chemotherapy in Chinese patients with T790M-negative NSCLC (N = 20), median PFS was longer with chemotherapy compared with anlotinib (4.5 vs 3.0 months; P = 0.021).…”

“… 100 Median PFS and OS were 5.4 and 16.1 months in the chemotherapy group versus 3.4 and 12.8 months in the TKI group, respectively. 100 Similarly, in a study comparing the efficacy of anlotinib versus chemotherapy in Chinese patients with T790M-negative NSCLC (N = 20), median PFS was longer with chemotherapy compared with anlotinib (4.5 vs 3.0 months; P = 0.021). 101 Furthermore, the Afatinib plus Bevacizumab Combination study demonstrated the efficacy and safety of this combination therapy in patients with NSCLC with acquired resistance to EGFR TKIs, regardless of T790M status (N = 32, including 14 with T790M-positive and 18 with T790M-negative NSCLC).…”

The efficacy of immune checkpoint inhibitors in advanced EGFR-Mutated non-small cell lung cancer after resistance to EGFR-TKIs: Real-World evidence from a multicenter retrospective study

“…Although the development of thirdgeneration EGFR-TKIs has overcome approximately 60% of acquired resistance due to the EGFR T790M mutation (5,6), challenges still exist in treatments after failure of thirdgeneration TKIs or firstand second-generation TKIs without T790M. Progression-free survival (PFS) with traditional chemotherapy in the subsequent lines of treatment is a disappointing length of 4.4-5.4 months (7,8). New strategies are urgently needed to improve the prognosis of patients who are resistant to EGFR-TKI therapy.…”