co-mutations as an independent prognostic factor in 2nd and further line therapy- mutated non-small cell lung cancer IV patients treated with osimertinib.

Background: The negative prognostic and predictive value of co-mutations ( mt+) in mutated ( mt+) non-small cell lung cancer (NSCLC) is increasingly being acknowledged. Data consistently show that mt+ impact negatively on 1st line objective response rate (ORR), progression free survival (PFS) and overall survival (OS) with 1st and 2nd generation tyrosine kinase inhibitors (TKI). However, a negative predictive impact has not been shown for the 3rd generation TKI Osimertinib. Therefore, we investigated the impact of mt+ in mt+ NSCLC carrying a T790M resistance mutation and treated in 2nd/further lines with Osimertinib.

Methods: A total of 77 mt+ NSCLC IV patients carrying a T790M resistance mutation from two institutions were analyzed for mt+. Clinical data including sex, age, presence of CNS metastases, etc., as well as types of and mt+ were captured. PFS and OS were calculated from the start of Osimertinib.

Results: mt+ were found in 32/77 patients (42%). mt+ was a statistically significant independent negative predictive factor for PFS and OS. PFS for mt+ patients were 9 months 14 months for patients with wild-type (WT) (P<0.008). OS for mt+ patients was 16 months 24 months patients with WT (P<0.025).

Conclusions: mt+ have a negative impact on PFS and OS in a group of patients carrying a sensitizing mt+ and a T790M resistance mutation treated with Osimertinib. These data, together with the data for 1st/2nd generation TKI in 1st line treatment call for additional therapeutic and management concepts for this subgroup of patients.