Abstract 1221P
Background
In patients (pts) with epidermal growth factor receptor mutant (EGFR+) non-small cell lung cancer (NSCLC) and de novo brain metastases (BM), whether addition of upfront (Uf) radiotherapy (RT) to EGFR tyrosine kinase inhibitor (TKI) is needed for optimal management remains controversial. We investigated clinical outcomes of EGFR+ pts with BM based on their Uf BM treatment (BM-Tx).
Methods
This is a single-centre retrospective analysis of 404 pts diagnosed with EGFR+ NSCLC and de novo BM between 2005-2019, who received Uf BM-Tx: EGFR TKI / whole brain radiotherapy (WBRT) / stereotactic radiosurgery (SRS). Pts who did not receive BM-Tx, had incomplete clinical data or BM surgical resection were excluded. Overall survival (OS) and intracranial progression-free survival (iPFS) were measured from date of BM diagnosis (dx).
Results
Median age at BM dx was 63 (IQR 56 –70); 79.2% of pts were never-smokers, 61.4% female, 95.3% adenocarcinoma, and 81.2% with ECOG 1–2. Majority of pts had EGFR exon 19 (53.2%) and exon 21 (41.3%) mutations, 3.7% pts harboured dual EGFR mutations. Uf BM-Tx was TKI in 47.3% pts, WBRT in 42.8% and SRS in 9.9%. Symptomatic BM were present in 23% pts in TKI group (grp), 63.6% in WBRT grp, 47.5% in SRS grp; and >10 BM were found in 36.9% pts, 63.4% and 0%, respectively. At median follow up of 55.5 months (m), OS was 36.2m in SRS grp (HR 0.54, p=0.004), 17.7m in WBRT grp (HR 1.27, p=0.036), vs 21.5m in TKI grp. Of 215 pts with CNS disease progression (PD), 43.3% received further salvage RT – 51.9% in Uf TKI grp, 21.3% in WBRT grp and 65.6% in SRS grp. Median RT-free period was 13.6m in pts who had Uf TKI with CNS-PD. In Uf TKI grp: 62.3% had 1st generation (1G), 19.9% 2G, and 17.8% 3G TKI; OS was 18.1m, 26.4m, and 20.7m, respectively (p=0.116). Median iPFS was similar – TKI grp (12.7 m), WBRT (12.9 m), SRS (17.5 m), p=0.195. On multivariate analysis, only ECOG 2-4 at BM dx (HR 1.59, p=0.002) and LMD (HR 1.90, p=0.042) were associated with shorter OS.
Conclusions
We demonstrated that with effective salvage options, Uf EGFR TKI alone is a reasonable BM-Tx approach in EGFR+ NSCLC pts with de novo BM regardless of TKI type, with long RT-free period and RT-sparing in some pts. Uf WBRT was associated with poorer survival outcomes but this may be confounded by high BM burden in this subgroup.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D.S.W. Tan: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other: Bristol Myers Squibs; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Sponsor/Funding: Novartis; Financial Interests, Personal, Funding: Boehringer Ingelheim. K.L.M. Chua: Financial Interests, Personal, Advisory Role: Peervoice; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Peervoice. All other authors have declared no conflicts of interest.