Abstract 167P
Background
KRAS G12C mutation has recently become a targetable alteration for patients with lung adenocarcinoma (LUADs). However, it is still unknown if targeted treatment might be preferable to immunotherapy in these tumors. OBJECTIVE: We aimed to assess clinical, pathological characteristics, and outcomes on immunotherapy for tumors harboring KRAS G12C mutation compared to other KRAS mutations, other targetable genomic alterations, and tumors with no targetable alterations.
Methods
Patients with LUADs treated with immunotherapy were prospectively included between January 2017 and July 2020. Clinicopathological and molecular data were collected and interrogated to evaluate associations between patients' characteristics, treatment response and survival outcomes.
Results
Table: 167P
| Characteristics (n=89) | n (%) |
| Age median (range) | 64 (range 40-78) |
| Sex | |
| Male | 70 (78.6) |
| Female | 19 (21.3) |
| Tobacco | |
| Never smoker | 6 (6.7) |
| Former smoker | 34 (38.2) |
| Current smoker | 49 (55) |
| Tumor stage (8th Edition) | |
| I | 2 (2.2) |
| II | 7 (7.9) |
| III | 13 (14.6) |
| IV | 67 (75.2) |
| Molecular Alterations | |
| No targetable alterations | 53 (59.5) |
| KRAS mutations | 24 (26.9) |
| EGFR mutations | 1 (1.1) |
| MET (amplification or exon skipping)) | 5 (5.6) |
| BRAF (Thr599dup, V600E and G469A) | 3 (3.3) |
| RET rearrangement | 1 (1.1) |
| NTRK rearrangement | 1 (1.1) |
| HER2 mutation | 1 (1.1) |
| Tumor PD-L1 % | |
| <1% | 31 (34.8) |
| 1-49% | 18 (20.2) |
| ≥50% | 31 (34.8) |
| NA | 9 (10.1) |
KRAS mutations were detected in 24 patients, with KRAS G12C representing 58.3% of all KRAS mutations, followed by KRAS G12A, G12V, G12F and G13C (16.6%, 16.6%, 4.2% and 4.2% respectively). LUADs harboring KRAS G12C mutations displayed higher frequency of tumors with PD-L1≥50% (n=7, 50%) and less PD-L1 negative tumors (n=1, 16.25%) compared with patients with KRAS non-G12C mutations (n=2, 18.18% and n=6, 54.54% respectively, p=0.036). Overall response rate to immunotherapy was 31.25% for KRAS G12C mutated patients, compared with 18.2% (p=0.65) in other KRAS mutations. The median follow-up of this population was 16.6 months. Survival analysis showed a trend towards a better OS in KRAS G12C tumors compared with tumors harboring KRAS non-G12C mutations (16.32 vs 9.7months, respectively, p=0.34).
Conclusions
LUADs harboring KRAS G12C mutations displayed higher PD-L1 expression compared to other KRAS mutations and seem to benefit more from immunotherapy. Additional biomarkers might be helpful in selecting the best therapy for patients harboring KRAS G12C mutations.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Taus: Non-Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Non-Financial Interests, Personal, Invited Speaker: MSD; Non-Financial Interests, Personal, Invited Speaker: GSK; Non-Financial Interests, Personal, Invited Speaker: Astra-Zeneca; Non-Financial Interests, Personal, Invited Speaker: Pfizer. B. Bellosillo: Non-Financial Interests, Personal, Invited Speaker: Amgen; Non-Financial Interests, Personal, Invited Speaker: Astra-Zeneca; Non-Financial Interests, Personal, Invited Speaker: Biocartis; Non-Financial Interests, Personal, Invited Speaker: Janssen; Non-Financial Interests, Personal, Invited Speaker: Merck-Serono; Non-Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Personal, Invited Speaker: Qiagen; Non-Financial Interests, Personal, Invited Speaker: Hoffman –La Roche; Non-Financial Interests, Personal, Invited Speaker: ThermoFisher; Non-Financial Interests, Personal, Invited Speaker: Pfizer; Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. E. Arriola: Non-Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Non-Financial Interests, Personal, Invited Speaker: MSD; Non-Financial Interests, Personal, Invited Speaker: Astra Zeneca; Non-Financial Interests, Personal, Invited Speaker: Pfizer; Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Personal, Invited Speaker: Lilly. All other authors have declared no conflicts of interest.