Open AccessAssociation of Programmed Death‐Ligand 1 Expression with Fusion Variants and Clinical Outcomes in Patients with Anaplastic Lymphoma Kinase‐Positive Lung Adenocarcinoma Receiving Crizotinib
Author(s) -
Yang ChingYao,
Liao WeiYu,
Ho ChaoChi,
Chen KuanYu,
Tsai TzuHsiu,
Hsu ChiaLin,
Liu YiNan,
Su KangYi,
Chang YihLeong,
Wu ChenTu,
Liao BinChi,
Hsu ChiaChi,
Hsu WeiHsun,
Lee JihHsiang,
Lin ChiaChi,
Shih JinYuan,
Yang James ChihHsin,
Yu ChongJen
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2020-0088
Subject(s) - crizotinib , medicine , anaplastic lymphoma kinase , hazard ratio , epidermal growth factor receptor , immunohistochemistry , oncology , cancer research , adenocarcinoma , lung cancer , pathology , cancer , confidence interval , malignant pleural effusion
Background Programmed death‐ligand 1 (PD‐L1) expression is associated with clinical outcomes of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (ADC) treated with tyrosine kinase inhibitors (TKIs). However, whether PD‐L1 expression plays a role in anaplastic lymphoma kinase (ALK)‐positive lung ADC is unknown. We aimed to evaluate the impact of PD‐L1 in patients with ALK‐positive lung ADC receiving crizotinib. Materials and Methods PD‐L1 expression was identified by immunohistochemistry (IHC). Reverse transcriptase‐polymerase chain reaction was used for ALK variant detection, and immunofluorescence‐based multiplex staining was applied for exploring immune cells in tumor microenvironments. Results A total of 78 patients with ALK‐positive advanced ADC were enrolled in our study, of whom 52 received crizotinib. Compared with EGFR/ALK wild‐type tumors, PD‐L1 expression was lower in ALK‐positive ADC. ALK fusion variants were identified in 32 patients, and those with variant 3 and 5 (short variants) had higher PD‐L1 expression than those with other variants. The crizotinib objective response rate (ORR) and progression‐free survival (PFS) was better in tumors with negative PD‐L1 expression (ORR/PFS in PD‐L1 0% vs. 1%–49% vs. 50%–100%: 60.7%/11.8 months vs. 38.5%/6.5 months vs. 36.4%/4.0 months, p = .007/.022). The multivariate Cox proportional hazards model revealed that PD‐L1 0% (vs. ≥1%) was an independent factor for longer PFS (adjusted hazard ratio 0.322, 95% confidence interval 0.160–0.650, p = .002). Multiplex IHC in three cases showed a varied extent of immune cell infiltrations in tumors with different PD‐L1 expression. Conclusion Positive PD‐L1 expression was associated with unfavorable clinical outcomes in patients with ALK‐positive lung ADC receiving crizotinib. Implications for Practice Not all lung adenocarcinoma with sensitizing driver mutations experienced durable responses to small‐molecule tyrosine kinase inhibitors (TKIs). Similar to the negative impact of programmed death‐ligand 1 (PD‐L1) in epidermal growth factor receptor mutant tumors treated with TKIs, this study demonstrated that positive PD‐L1 expression was also associated with worse response rate and shorter progression‐free survival of anaplastic lymphoma kinase (ALK)‐positive adenocarcinoma treated with crizotinib. Among different ALK fusion partners, tumors with short variants (V3 and V5) had higher PD‐L1 compared with long variants (V1, V2, and V6). Testing PD‐L1 before initiating crizotinib for ALK‐positive lung cancer could be a simple method to provide important prognostic information.