Early-stage KRAS G12C-mutated non-small cell lung cancer (NSCLC) in Australia.

Abstract

e21053 Background: KRAS is frequently mutated in NSCLC, especially in Caucasian populations. Until recently there have not been effective targeted therapies against KRAS but the recent advent of active agents has thrown a spotlight on this disease. Methods: A database of NSCLC cases undergoing lobectomy or pneumonectomy with curative intent at Austin Health, Victoria, Australia was examined. Analysis for KRAS mutations was carried out using the LungCarta panel. Results: Four hundred and fifty nine cases underwent mutation analysis and 203/459 (44%) were wild type. KRAS mutations were identified in 100/459 cases (21.8%), including 3 cases where the specific mutation was not specified. KRAS G12C cases comprised 40/97 (8.5% of all cases, 41% of specified mutation KRAS cases) and other KRAS mutations comprised 57/97 (59%) - most commonly G12V (25 cases) and G12D (13 cases). Additional mutations were identified in 14/40 (36%) G12C mutation cases (10 dual and 4 triple – most commonly TP53 9, STK11 3 and PIC3CA 2). In non-G12C cases, multiple mutations were identified in 24% of cases. Considering the 40 G12C cases, histology was squamous cell in 21 cases, adenocarcinoma 13 and other 5. Males comprised 21/40 cases, median age at diagnosis was 61 year (range 34 – 78), with stage I 22 cases, stage II 12; stage IIIA 5 and one stage 4 (solitary brain metastasis). Thirty six patients (90%) had smoked tobacco with median exposure of 44 pack years (range 13-100) including 18 ex-smokers who had ceased a median 9 years (range 1 - 28) prior to the diagnosis of lung cancer. PD-L1 expression was analysed using the 28-8 antibody. For the 38 cases analysed, PD-L1 expression was ≥ 50% in 6 (16%), ≥ 5% in 12 (32%) and < 1% in 24 (63%). The estimated median overall survival was 4.9 years with 27% 10 year survival. Twenty three patients (58%) died from the index lung cancer, 8 (20%) remain alive and 9 (23%) died of other causes: 4 from a 2nd lung cancer, 4 from a non-lung cancer and one from liver failure. Data on sites of recurrence were available for 16 of the 23 cases who died from the index lung cancer, with initial recurrence sites being lung/local 7 patients, brain 6, bone 2, liver 1. A total of 9 patients (56%) developed brain metastases at some time. Conclusions: KRAS G12C is a common subgroup of NSCLC in the Australian population and almost all of cases were tobacco smokers. Additional mutations were identified in over a third of cases. Locally recurrent disease or brain metastases are the most frequent sites of relapse and over half of patients with recurrent disease develop brain metastases.