Survival Of Patients With Non-Small Cell Lung Cancer And Exon 20 Insertion Mutation From The Czech Republic

Patients with NSCLC harboring Exon 20 insertion mutation have unknown prognosis compared to patients with other mutation types. Unlike other EGFR mutations, Exon 20 insertion mutations are generally insensitive to EGFR TKIs. To analyze this, data were taken from the TULUNG registry, which collects epidemiological and clinical data from patients treated with targeted therapy in Czech Republic with advanced NSCLC since 2011. Data from 5863 patients were considered for the analysis, with 2820 tested for EGFR mutation, 672 (23.8%) testing positively. Mutation on Exon 20 was found in 95 (14.1%) patients. Out of these patients 26 (27.4%) had Exon 20 insertion, other types of mutation were T790M in 55 (57.9%) and S768I in 14 (14.7%) patients. Kaplan-Meier method was used to analyze OS and PFS. The survival of patients with insertion was compared to the other Exon 20 mutations using a log-rank test. The effects of gender, age, smoking, were tested with Cox models. The presence of other mutations was also evaluated. The analysis was performed for patients on their first line of targeted therapy and then for those on second line. Patients with Exon 20 insertion had significantly worse OS (2 years: 40.1% (22.3–72.1) vs. 66.2% (55.0–79.7); log-rank: p = 0.01) and PFS (1 year: 20.6% (9.0–47.0) vs. 44.5% (34.0–58.2); log-rank: p = 0.013) from the start of first targeted therapy compared to patients with the other Exon 20 mutations. The same was seen in patients on second treatment in PFS (1 year: 7.1% (1.1–46.8) vs. 44.3% (31.7–61.9); log-rank: p = 0.002), but not in OS (2 years: 9.9% (1.6–63.2) vs. 38.1% (24.2–59.9); log-rank: p = 0.058). Age, gender and the presence of additional mutations did not have a significant effect on the OS and PFS in any of the models examined. Smoking was found significant – with current and former smokers having lower survival – in some models. The analysis found statistically significantly worse PFS and OS for patients with Exon 20 insertion compared to other Exon 20 mutations. As an additional factor, smoking was observed to negatively affect survival generally in all patients with Exon 20 mutations on both their first and second targeted treatment.