55P Differences in response to immune treatment between KRAS G12C and KRAS non-G12C mutated non-small cell lung cancer

Non-small cell lung cancer (NSCLC) can harbor different KRAS mutations. Although targeted therapy is available for KRAS G12C-mutant (mt) NSCLC, immune checkpoint inhibitors (ICIs) are still the first line treatment (tx) for these patients (pts). Here we aimed to assess the outcomes on ICIs for KRAS G12C compared to KRAS non-G12C-mt pts. This is an updated observational, retrospective, multicenter study of pts with KRAS-mt NSCLC treated with ICIs between January 2017 and October 2023. 14 pts received anti-KRAS G12C tx. Targeted sequencing was performed in 59% cases and polymerase chain reaction in the rest. Clinicopathological and molecular data were collected. We evaluated the characteristics, tx response and survival outcomes on ICIs of pts with KRAS G12C vs non-G12C-mt tumors. 189 pts were included with a median follow-up of 34.3 months (m). STK11 and TP53 were the most frequent co-mutated genes present in 4.3%/18.5% G12C/non-G12C and 21.3%/44.7% G12C/non-G12C, respectively. In all KRAS mt tumors, harboring a TP53 co-mutation was associated to a positive PD-L1 and a better ECOG (p < 0.001 and p=0.006, respectively). In addition, a trend to a better overall survival (OS) was seen in TP53 vs STK11 tumors (14.7 vs 6.1m, respectively, p = 0.195). No differences were seen in the median duration of response or progression free survival between G12C/non-G12C (10.7 vs 9.5m p=0.202 and 8 vs 5m p= 0.554, respectively). KRAS G12C tumors were associated with a better median OS compared with non-G12C tumors (16.2 vs 9.2m p=0.024). In the multivariate analysis for OS, PD-L1 negative tumors and ECOG ≥1 were independently associated with worse OS (p=0.004 and p<0.001, respectively).Table: 55PN (%)G12C (n=92)Non-G12C (n=97)p-valueMedian age (range)62.9 (61.8-64.9)65 (63-66.3)Sex0.237Male36 (39.1)67 (69.1)Female56 (60.9)30 (30.9)Tobacco0.866Former47 (51.1)49 (50.5)Current44 (47.8)46 (47.4)Stage0.530I-III18 (19.6)23 (23.7)IV74 (80.4)74 (76.3)M1 CNS17 (18.5)26 (26.8)0.172M1 liver16 (17.4)19 (19.6)0.698ICIs treatment line0.466172 (78.3)80 (82.5)≥220 (21.7)17 (17.5)PD-L10.234Negative (0%)22 (23.9)32 (33)Positive (≥1%)64 (69.6)63 (65)ECOG0.241034 (37)44 (45.4)≥158 (63)53 (54.6) Open table in a new tab Our work shows that pts with KRAS G12C tumors are associated with better OS on ICIs tx when compared with pts with KRAS non-G12C tumors. Harboring a TP53 co-mutation associated to a KRAS mutation might determine a different tumor microenvironment and therefore a better response to ICI tx.