Genomic landscape of NSCLC with no targetable driver mutation among different races: An exploratory analysis of the AACR Project GENIE Database.

Abstract

8041 Background: Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer, and it has been historically associated with poor prognosis. Fortunately, recent advancements in targeted therapies have significantly improved the prognosis of this disease. However, around 40% of those diagnosed with NSCLC do not harbor a targetable oncogenic driver mutation. This percentage is not consistent among all races, as those who are eastern Asian or from eastern Asian descent have higher rates of targetable drivers and a unique genomic signature that makes them distinct to others. Even though Asians have higher rates of targetable NSCLC, about 20% of Asians diagnosed with NSCLC do not harbor targetable mutations. This raises the need to study the genomics of non-targetable NSCLC in different races to understand the nature of the disease and have a more precise understanding of its behavior in different populations. Methods: The Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR-GENIE) cohort v17.0-public registry was queried to study patients diagnosed with non-targetable NSCLC (n = 16,866). Non-targetable NSCLC was defined as NSCLC that does not harbor targetable driver mutation for the following genes (EGFR, NTRK1/2/3, KRAS, BRAF, MET, RET, NRG1, ERBB2) The patients were divided into three racial groups: White (85.2%), Black (9.5%), and Asian (5.3%). cBioportal was used to study the genetic mutations and clinical differences between the groups. Black & White groups were merged due to the patients’ disease having similar genomic features and the group was named non-Asian (94.7%). Chi-squared test was used to measure the relationship between mutation frequencies between different groups. Results: A higher proportion of Asian patients with non-targetable mutations were males compared to the non-Asian group (61.96% vs 47.54%,P < 0.001). The most significant differences were found in 4 genes: KRAS (Asian 21.16%, non-Asian 30.22%, P < 0.001), STK11 (Asian 9.88%, non-Asian 17.58%, P < 0.001), KEAP1 (Asian 13.61%, non-Asian 20.50% ,P < 0.001), and TERT (Asian 12.22%, non-Asian 7.56%, P < 0.001). There was a significant difference in the prevalence of TP53 mutations (Asian 52.13%, non-Asian 56.31%, P = 0.0232). Conclusions: Among non-targetable driver mutations, KRAS, KEAP1, STK11 and TP53 were less frequent in the Asian group vs non-Asian, while TERT was higher in the Asian group. These differences can be explained by variation in carcinogens exposure (smoking rates) and the unique genetic profile between ethnicities. It supports the significance of ethnicity and racial background even in the era of precision medicine.