Clinical Characteristics and Outcomes in Advanced KRAS-Mutated NSCLC: A Multicenter Collaboration in Asia (ATORG-005)

Introduction: Whereas interpatient heterogeneity in clinical characteristics and treatment outcomes of NSCLC harboring a KRAS mutation is recognized, the characterization of these patients in Asia has been limited.

Methods: A multicenter, retrospective cohort study was conducted in eight academic centers across Asia. Patients diagnosed with advanced NSCLC harboring a KRAS mutation and who had received at least one line of anticancer therapy between January 2014 and December 2018 were included. Modified time to next treatment (TTNT) was adopted as a proxy for progression-free survival.

Results: A total of 216 patients were analyzed. The median age at diagnosis of advanced NSCLC was 63.3 years, 70.8% were men and 89.8% had adenocarcinoma. KRAS G12D was the most common subtype (25.5%), followed by G12C (24.5%), and G12V (19.4%) The proportion of current or former smokers was 65.7% in the overall population, with 86.8% in G12C and 58.9% in non-G12C subgroups. For all treatments combined for the total population, the first-line duration of therapy, modified TTNT, and TTNT were 4.5 (95% confidence interval: 3.4-5.9), 6.2 (4.9-8.8), and 9.5 (7.1-11.4) months, respectively. The median overall survival for the total population was 10.3 (6.9-12.4) months and was prolonged in patients ever treated with immunotherapy (14.6 [8.6-19.1] versus 7.0 [5.9-10.6] mo, hazard ratio = 0.54, p < 0.001), with left truncation to account for the time of KRAS testing.

Conclusions: Whereas treatment outcomes with conventional anticancer therapy are reasonable and immunotherapy looks promising, the unmet need remains high for patients with KRAS-mutated NSCLC in Asia, underscoring the need for novel therapeutic approaches.