Abstract 193P
Background
Distinct KRAS mutations subtypes can be found in NSCLC (Non-small cell lung cancer). Targeted therapy has become a treatment choice for patients with KRAS G12C NSCLC although immunotherapy (ICI) is widely used in these patients with good outcomes in a subset of patients. Response to immunotherapy of non-KRAS G12C NSCL is less characterized. Here we aimed to assess the outcomes on immunotherapy for patients with tumors harboring KRAS G12C mutation compared to other KRAS mutations.
Methods
Patients with KRAS mutant NSCLC treated with immunotherapy between January 2017 and November 2022 were included in this study. Clinicopathological, molecular and clinical outcome data were collected and interrogated to evaluate associations between patients’ characteristics, treatment response and survival outcomes from the beginning of ICI.
Results
A total of 71 patients with NSCLC patients with KRAS mutation were included. KRASG12C mutation was detected in 33 patients, representing 46.5% of all KRAS mutations. With a median follow-up for the overall population of 33.82 months, survival analysis showed an improved overall survival (OS) in KRAS G12C tumors compared with tumors harboring KRAS non-G12C mutations (16.9 vs 5.4 months, respectively, p = 0.02). Overall response rate (ORR) to immunotherapy was 66.7% for KRAS G12C mutated patients, compared with 42.1% (p = 0.41) in patients with other KRAS mutations. No differences in median OS were seen between KRAS G12C with and without TP53 co-mutation (17.8 vs 16.9 months, respectively, p = 0.8), neither in KRAS non-G12C (6 vs 5.2 months, respectively, p = 0.52). No significant statistically differences in PD-L1 expression were observed between KRAS G12C and KRAS non-G12C groups (p = 0.14).
Table:193P
| Characteristics | KRAS G12C(n = 33) | KRAS non-G12C(n = 38) |
|---|---|---|
| Age median (range) | 62 (41–73) | 61 (55–83) |
| Sex (%) | ||
| Male | 22 (66.6) | 31 (81.6) |
| Female | 11 (33.3) | 7 (18.4) |
| Tobacco (%) | ||
| Never smoker | 1 (2.8) | 1 (2.6) |
| Former smoker | 11 (43.7) | 20 (52.6) |
| Current smoker | 21 (53.5) | 17 (44.7) |
| Tumor stage (8th Edition) (%) | ||
| I | 2 (6) | 3 (7.9) |
| II | 2 (6) | 1 (2.6) |
| III | 7 (21.21) | 6 (15.8) |
| IV | 22 (66.6) | 28 (73.7) |
| Co mutations (%) | ||
| TP53 | 10 (30.3) | 15 (39.5) |
| STK11 | 1 (3) | 2 (5.3) |
| BRAF G469 V | 1 (3) | 0 (0) |
| PI3 K | 0 (0) | 1 (2.6) |
| CTNNB1 | 0 (0) | 1 (2.6) |
| ERBB4 | 0 (0) | 1 (2.6) |
| FBXW7 | 0 (0) | 1 (2.6) |
| SMAD4 | 0 (0) | 1 (2.6) |
| Treatment line (ICI) | ||
| 1 | 16 (48.5) | 27 (71.1) |
| 2 | 15 (45.5) | 11 (28.9) |
| 3 | 1 (3.0) | 0 (0) |
| NA | 1 (3.0) | 0 (0) |
Conclusions
Although a better overall survival in patients harboring KRAS G12C tumors was observed in our study, more biomarkers might be helpful to predict more accurately the response to immunotherapy and select the best treatment for each patient.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Masfarre Pinto: Non-Financial Interests, Personal, Invited Speaker: AstraZeneca. N. Navarro Gorro: Non-Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel Fees: MSD. A. Corbera Lloret: Financial Interests, Personal, Invited Speaker, Travel expenses: Merck, MSD, BMS; Financial Interests, Personal, Invited Speaker: Astellas, Janssen. A. Taus Garcia: Non-Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, GSK, AstraZeneca, Pfizer. B. Bellosillo Paricio: Non-Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Biocartis, Janssen, Merck-Serono, Novartis, Qiagen, Hoffman –La Roche, ThermoFisher, Pfizer, BMS. E. Arriola: Non-Financial Interests, Personal, Other, Grant: Roche, Pfizer; Non-Financial Interests, Personal, Other, Personal Fees: Roche, BMS, MSD, AstraZeneca, Pfizer, Boehringer Ingelheim, Eli Lilly, Takeda. All other authors have declared no conflicts of interest.