Abstract 55P
Background
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.
Methods
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.
Results
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: 55P
| N (%) | G12C (n=92) | Non-G12C (n=97) | p-value |
| Median age (range) | 62.9 (61.8-64.9) | 65 (63-66.3) | |
| Sex | 0.237 | ||
| Male | 36 (39.1) | 67 (69.1) | |
| Female | 56 (60.9) | 30 (30.9) | |
| Tobacco | 0.866 | ||
| Former | 47 (51.1) | 49 (50.5) | |
| Current | 44 (47.8) | 46 (47.4) | |
| Stage | 0.530 | ||
| I-III | 18 (19.6) | 23 (23.7) | |
| IV | 74 (80.4) | 74 (76.3) | |
| M1 CNS | 17 (18.5) | 26 (26.8) | 0.172 |
| M1 liver | 16 (17.4) | 19 (19.6) | 0.698 |
| ICIs treatment line | 0.466 | ||
| 1 | 72 (78.3) | 80 (82.5) | |
| ≥2 | 20 (21.7) | 17 (17.5) | |
| PD-L1 | 0.234 | ||
| Negative (0%) | 22 (23.9) | 32 (33) | |
| Positive (≥1%) | 64 (69.6) | 63 (65) | |
| ECOG | 0.241 | ||
| 0 | 34 (37) | 44 (45.4) | |
| ≥1 | 58 (63) | 53 (54.6) |
Conclusions
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.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Castro Unanua: Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Travel: Roche; Financial Interests, Personal, Other, Travel:MSD, Lilly. P.F. Simoes Da Rocha: Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Personal, Other, Travel Suport: MSD, BMS, Kiowa Kirin. A. Taus Garcia: Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, MSD, Pfizer, GSK, Takeda; Financial Interests, Personal, Advisory Board: Sanofi, GSK; Financial Interests, Personal, Other, Travel Suport: GSK, MSD, AstraZeneca. B. Bellosillo Paricio: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Merck-Serono, Novartis, Roche, Thermo Fisher, Pfizer, BMS; Financial Interests, Personal, Other, Research Grants: Thermo Fisher, Roche Diagnostics, Roche Farma. H. Arasanz: Financial Interests, Personal, Other, Clinical Trial Coordinator: Ferrer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Takeda, MSD; Financial Interests, Personal, Other, Travel Support: BMS, Angelini Pharma, Roche. E. Arriola: Financial Interests, Personal, Advisory Board: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda; Financial Interests, Personal, Speaker’s Bureau: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda; Financial Interests, Personal, Other, Cofounder: Trialing Health S.L. All other authors have declared no conflicts of interest.