Abstract 204P
Background
Molecular-guided treatments are increasingly shaping the management of localised non-small cell lung cancer (NSCLC), emphasising the need to better understand the characteristics and outcome impact of KRAS mutations in this context.
Methods
This is an update of a retrospective, real-world, single-centre study analysing stage 1–3 NSCLC patients (pts) treated with radical radiotherapy (RRT) (≥40 Gy, ≥15 fractions) between 07/21 and 04/24. Pts with a known KRAS mutation (mt) or next generation sequencing analysis and no other drivers were included. Baseline characteristics, and relapse-free survival (RFS) were compared between KRAS mt and wildtype (wt) pts.
Results
202 NSCLC pts were included: 102 KRAS wt, 100 KRAS mt. The median follow-up was 23 months (m). The KRAS mt group had significantly more women and higher median PD-L1 levels (31% vs 22%, p < 0.001; 39% vs 0%, p=0.0001; respectively). Non-adenocar-cinoma histology was more frequent in the wt group (29% vs 8%, p < 0.001). On Cox univariate analysis, these variables did not show a significant impact on RFS outcomes. The table shows treatment and molecular characteristics. The median RFS for all stages was 14 m for KRAS mt and 12 m for wt (p=0.107). Among stage 3 pts, the median RFS for KRAS mt and wt were: not reached (NR)/16 m for concurrent (CCRT); 11/10 m for sequential chemoradiotherapy (SCRT) and 10/12 m for radiotherapy (RT) alone, respectively. A higher proportion of KRAS mt pts received maintenance durvalumab (32.4% vs 15.7% wt). When pts treated with durvalumab were excluded, CCRT outcomes were similar between groups (11 vs 12 m for wt). Codon Q61 pts showed better RFS (NR vs 19 m for G12 and 8 m for G13).
Table 204P| Stage I-II (n=51) | Stage IIIA-C (n=138) | ||||
| KRAS wt (n=102) | Total (n,%) Treatment (n,%) | 25 (49%) 23 (92%) primary RT alone 2 (8%) Adjuvant/after surgery − | 70 (51%) 31 (44%s) RT alone 22 (31%) CCRT 17 (24%) SCRT | ||
| KRAS mt (n=100) | Total (n,%) Treatment (n,%) | 26 (51%) 25 (96%) primary RT alone 1 (4%) adjuvant/after surgery − − | 68 (49%) 22 (32%) primary RT alone 2 (3%) adjuvant/after surgery 31 (46%) CCRT 13 (19%) SCRT | ||
| Subtype (n,%) | Codon 12 | G12C: 17 | Codon 12 (60, 88%) | G12C: 35 (51%) | |
| (23, 68%) | (68%) | ||||
| G12V: 2 (8%) | G12V: 12 (18%) | ||||
| G12D:3 | G12D: 8 (12%) | ||||
| (12%) | |||||
| G12A: 0 | G12A: 2 (3%) | ||||
| Other G12: | Other: 2 (3%) | ||||
| 1 (4%) | |||||
| Codon G13 | 0 | Codon 13 | 5 (7%) | ||
| Codon Q61 | 2 (8%) | Codon 61 | 4 (6%) | ||
Conclusions
Stage 3 KRAS mt pts might derive greater benefit from CCRT followed by durvalumab than KRAS wt. RT alone or SCRT show similar outcome regardless of KRAS status. KRAS codons might impact differently on RT outcomes. These findings are limited by the small sample size and should be interpreted cautiously.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Lindsay: Financial Interests, Personal, Invited Speaker, Advisory role: Amgen; Financial Interests, Personal, Invited Speaker, Educational Presentation/Workshop: Amgen; Financial Interests, Personal, Advisory Board: Qiagen; Financial Interests, Institutional, Invited Speaker, CI for a phase III clinical trial: Mirati Therapeutics, Amgen; Financial Interests, Institutional, Invited Speaker, CI for a phase I-II clinical trial: BI, Revolution Medicines; Financial Interests, Institutional, Invited Speaker, CI for a phase II clinical trial: Roche; Financial Interests, Institutional, Invited Speaker, PI for a phase II clinical trial: Apollomics; Financial Interests, Institutional, Research Grant, Research funding which includes use of their medical products: Revolution Medicines; Non-Financial Interests, Personal, Other, Travel funding for poster presentation: Boehringer Ingelheim; Other, Personal, Other, Review paper coordinated by Amgen. Initially drafted by other writers, with contributions from co-authors.: Amgen. C. Faivre-Finn: Financial Interests, Institutional, Other, research-related advisory, steering committee, lectures: AstraZeneca; Financial Interests, Institutional, Other, research-related projects, advisory: Elekta; Financial Interests, Institutional, Other, Research-related funding: MSD. All other authors have declared no conflicts of interest.