Abstract 1949: KRAS G12C mutations in Hispanic and non-Hispanic patients with NSCLC: clinicopathologic characteristics and prognosis
Authors: Manoharan Aysswarya , Kareff Samuel A. , Ramos Leana M. , El-Abbar Nora A. , Lopes Gilberto , Rodriguez Estelamari 
Published: April 2023

Background: KRAS mutations, which are associated with tobacco use, have been linked to worse survival in patients with non-small cell lung cancer (NSCLC). KRAS G12C is the most frequent actionable mutation detected in NSCLC, with a prevalence of 13%. The incidence of KRAS G12C mutations and potential impact on treatment response for Hispanic patients with lung cancer has not been well characterized.

Methods: A total of 110 patients (77 non-Hispanic [NH] and 33 Hispanic) with a diagnosis of NSCLC and next generation sequencing information available treated at the University of Miami from 2013-2021 were included. Incidence of KRAS G12C mutations, clinicopathologic characteristics, treatment response and overall survival were analyzed.

Results: The prevalence of the KRAS G12C mutation was 7.6% in the whole cohort. The prevalence of KRAS G12C co-mutations in NH vs Hispanic was 9.3% vs 5.7%. Median age of NH vs Hispanic patients was 69.5 yrs vs 66.4 yrs. (Table 1) In both the NH and Hispanic cohorts, there were more women (56% vs 51.5%), as well as smokers (97% vs 97%). In both cohorts, most patients had non-squamous histology (94%). In the NH cohort, the majority were PDL1 negative (50%). In the Hispanic cohort, there was a more even distribution of PDL1 expression status: negative (30%), low (33%), and high (24%). Median DOR for chemotherapy in NH vs Hispanics was 16 mos vs 14 mos (p=0.77). Median DOR for immunotherapy in NH vs Hispanics was 18 mos vs 12 mos (p=0.30). Median OS in NH vs Hispanics was 36 mos vs 29 mos (p=0.25).

Conclusion: There was no statistical difference in prevalence of KRAS G12C mutations between NH and Hispanics. Notably, both cohorts had a significant smoking history. KRAS G12C portends equally poor prognosis and treatment resistance as evidenced by median DOR and OS for both Hispanics and NH patients. However, Hispanic patients demonstrated a trend of decreased OS and DOR to IO compared to NH patients.

Clinicopathologic characteristics and prognosis of NH and Hispanic Patients with KRAS G12C mutation `Characteristic Non-Hispanic (n = 77) Hispanic (n =33 ) P Value Total Patients (%) 77 (70%) 33 (30%) Status 37(48%) 14(42%) Alive(%) 40(52%) 19(58%) Deceased(%) Median Age (Years [Range]) 69.5 (47-92) 66.4 (41-84) 0.13 Gender 34(44%) 17(52%) Male(%) 43(56%) 16(48%) Female(%) Race 70(91%) 32(97%) White(%) 4(5%) 1(3%) African American(%) 1(1%) 0(0%) Asian (%) 2(3%) 0(0%) Other(%) Tobacco Use 2(3%) 1(3%) Never(%)&lt;1 Pack/Day(%) 41(53%)34(44%) 18(55%)14(42%) &gt;1 Pack/Day(%) Histology 73(94%) 31(94%) Non-squamous(%) 2(3%) 0(0%) Squamous(%) 2(3%) 2(6%) Mixed/Other(%) PD-L1 Status 39(50%) 10(30%) Negative(%) 13(17%) 11(33%) Low expression(&lt;50%)(%) 13(17%) 8(24%) High expression(&gt;50%)(%) 12(16%) 4(13%) Unknown(%) Stage 1(1%) 1(3%) IA(%) 5(6%) 2(6%) IB(%) 3(4%) 0(0%) IIA(%) 4(5%) 3(9%) IIB(%) 11(15%) 4(12%) IIIA(%) 4(5%) 0(0%) IIIB(%) 46(60%) 22(67%) IV(%) 3(4%) 1(3%) Unknown(%) Metastases* 487(12%) 265(17%) Any metastasis/multiple sites 2(4%) 0(0%) Lung 5(9%) 3(11%) Liver 13(22%) 7(25%) Adrenal 18(31%) 9(33%) Bone 13(22%) 4(14%) Brain Other Chemotherapy 20(26%) 10(31%) No Chemotherapy(%) 28(36%) 12(36%) Platinum + Pemetrexed(%) 6(8%) 1(3%) Platinum + Taxane(%) 4(5%) 8(24%) Chemotherapy + Immunotherapy(%) 9(12%) 1(3%) Single Agent Chemotherapy(%) 10(13%) 1(3%) Unknown(%) Median duration of response to chemotherapy 14 months 16 months 0.77 Immunotherapy 27(35%) 18(54%) Yes(%) 40(52%) 13(40%) No(%) 10(13%) 2(6%) Unknown(%) Median duration of response to immunotherapy 18 months 12 months 0.30 Median Survival Time 36 months 29 months 0.25 Median Survival Time in Stage IV Patients 29 months 20 months 0.92 *Percentages may not equal 100

Citation Format: Aysswarya Manoharan, Samuel A. Kareff, Leana M. Ramos, Nora A. El-Abbar, Gilberto Lopes, Estelamari Rodriguez. KRAS G12C mutations in Hispanic and non-Hispanic patients with NSCLC: clinicopathologic characteristics and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1949.