Abstract 70P
Background
Mutations in TP53 and KRAS are frequent in NSLC pts, particularly in non-squamous histology. Improved biomarkers for treatment selection are needed. We aimed to investigate the impact of TP53 and KRAS mutation on treatment outcome of pts with first-line systemic therapy for mNSCLC.
Methods
Single-institution retrospective cohort of mNSCLC pts treated with ≥1 line of systemic therapy. A targeted NGS panel (Oncomine Precision) including KRAS and TP53 was performed on all pts; actionable EGFR, ALK, ROS-1 alterations were excluded. PDL1 was assessed by IHC (SP263 Ab). The main objective was to study the association between TP53 and/or KRAS mutations and OS (overall population, and in PDL1 ≥ 50% and PDL1 < 50% populations). OS was defined as the time from therapy start to last visit or death. Kaplan-Meier method was used to calculate median OS; associations with OS were assessed through Cox-regression models.
Results
68 mNSCLC pts were included. Most had non-squamous histology (92.5%), ECOG PS 0–1 (81%) and PDL1 < 50% (81%). TP53 and KRAS mutations were observed in 34.3% and 23.9%, respectively; 3% had co-occurring mutations. 52% received chemo-immunotherapy combinations and 20% immunotherapy. Median OS was 9.8 months (95%CI: 6.8-NR). In the overall population, a non-significant trend was observed for higher OS in TP53-mutated pts (HR 0.5; p = 0.058). There was a significant OS benefit in TP53 mutated pts with PDL1 < 50% (HR: 0.44; 95%CI: 0.20–0.98; p = 0.043), but not in PDL1 ≥ 50% (HR 0.89; 95%CI: 0.10–7.7; p = 0.92) pts. No association between KRAS mutations and OS was observed (table).
Table: 70P| TP53 mutation | KRAS mutation | |||||
|---|---|---|---|---|---|---|
| Yes | No | HR (95%CI); pval | Yes | No | HR (95%CI); pval | |
| All pts | 18.4 m | 7.3 m | 0.50 (0.24–1.02); p = 0.058 | 7.3 m | 12.4 m | 1.5 (0.75–2.9); p = 0.25 |
| PDL1 < 50% | 18.4 m | 6.9 m | 0.44 (0.20–0.97); p = 0.043 | 8.9 m | 12.4 m | 1.3 (0.60–2.7); p = 0.49 |
Conclusions
We observed a statistically significant difference in OS favouring pts with TP53 mutations in the PDL1 < 50% population. No survival impact of KRAS mutations was observed. TP53 mutations could represent a potential biomarker for treatment selection for pts with low PDL1 expression treated with chemo-immunotherapy. Prospective validation is needed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.