Abstract 718P
Background
Around 8-10% of lung cancer cases are ALK-positive, mostly with EML4-ALK fusions. ALK TKIs have improved outcomes for metastatic lung adenocarcinoma patients, but response rates vary. We retrospectively studied the relationship between different ALK fusions and PD-L1 expression and their effect on outcomes in NSCLC.
Methods
A retrospective analysis of data from 254 advanced lung adenocarcinoma patients was conducted, and twenty-eight patients (11%) were deemed ALK-positive. ALK variants and accompanying mutations were identified through next-generation sequencing, and PDL1 expression was evaluated using IHC with the sP263 antibody. Findings were assessed, noting the relationship between progression-free survival (PFS) on ALK inhibitors and PDL1 expression.
Results
The median age of the patient cohort was 46 years (range 28-65). Twenty-eight out of 254 patients (11%) were deemed ALK-positive; most had EML4-ALK fusions, with V1 (50%), V3 (35.7%), and V2 (14.2%) being the most common. PD-L1 negativity was seen in 60.7%, while 39.3% were PD-L1 positive. PD-L1 negativity was more common in the V1 variant (p=0.0183), and PD-L1 positivity was associated with V3 (p=0.0204). V1 (35.7%) and V3 (40%) often had TP53 comutations. Patients treated with 1st-line ALK TKIs had a median PFS of V1 (22 months), V2 (19 months), and V3 (11 months). V1 patients with PD-L1 negativity had a median PFS of 25 months versus 11 months for PD-L1 positivity (p=0.001), but this significance was not seen in V2 and V3.
Conclusions
V1 and V3 are the most common gene variants in ALK-positive lung cancer. We observed a significant link between V1 and PD-L1 negativity and V3 and PD-L1 positivity. V3 patients had poor outcomes regardless of PD-L1 status, while V1 patients with PD-L1 negativity had better outcomes. These biomarkers offer key insights into treatment outcomes for ALK-positive patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.