Reference Detail

Ref Type

Journal Article

PMID

(32178965)

Authors

Schoenfeld AJ, Rizvi H, Bandlamudi C, Sauter JL, Travis WD, Rekhtman N, Plodkowski AJ, Perez-Johnston R, Sawan P, Beras A, Egger JV, Ladanyi M, Arbour KC, Rudin CM, Riely GJ, Taylor BS, Donoghue MTA, Hellmann MD

Title

Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology	31	5	2020 05	599-608	Ann Oncol

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Abstract Text

Programmed death-ligand 1 (PD-L1) expression is the only FDA-approved biomarker for immune checkpoint inhibitors (ICIs) in patients with lung adenocarcinoma, but sensitivity is modest. Understanding the impact of molecular phenotype, clinical characteristics, and tumor features on PD-L1 expression is largely unknown and may improve prediction of response to ICI.We evaluated patients with lung adenocarcinoma for whom PD-L1 testing and targeted next-generation sequencing (using MSK-IMPACT) was performed on the same tissue sample. Clinical and molecular features were compared across PD-L1 subgroups to examine how molecular phenotype associated with tumor PD-L1 expression. In patients treated with anti-PD-(L)1 blockade, we assessed how these interactions impacted efficacy.A total of 1586 patients with lung adenocarcinoma had paired PD-L1 testing and targeted next-generation sequencing. PD-L1 negativity was more common in primary compared to metastatic samples (P < 0.001). The distribution of PD-L1 expression (lymph nodes enriched for PD-L1 high; bones predominantly PD-L1 negative) and predictiveness of PD-L1 expression on ICI response varied by organ. Mutations in KRAS, TP53, and MET significantly associated with PD-L1 high expression (each P < 0.001, Q < 0.001) and EGFR and STK11 mutations associated with PD-L1 negativity (P < 0.001, Q = 0.01; P = 0.001, Q < 0.001, respectively). WNT pathway alterations also associated with PD-L1 negativity (P = 0.005). EGFR and STK11 mutants abrogated the predictive value of PD-L1 expression on ICI response.PD-L1 expression and association with ICI response vary across tissue sample sites. Specific molecular features are associated with differential expression of PD-L1 and may impact the predictive capacity of PD-L1 for response to ICIs.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 over exp TP53 mut	lung adenocarcinoma	predicted - sensitive	unspecified immune checkpoint inhibitor	Clinical Study - Cohort	Actionable	In a clinical study, lung adenocarcinoma patients with high expression of CD274 (PD-L1; >/= 50%) and a co-occurring TP53 mutation demonstrated a greater objective response rate, 39.8% (35/88) vs 18.3% (13/71); P=0.005, progression-free survival (HR=0.62, P=0.006), and overall survival (HR=0.65, P=0.04) compared to patients with negative expression of CD274 (PD-L1) and a co-occurring KRAS mutation when treated with an unspecified immune checkpoint inhibitor (PMID: 32178965).	32178965
CD274 over exp STK11 mut	lung adenocarcinoma	not predictive	unspecified immune checkpoint inhibitor	Clinical Study - Cohort	Actionable	In a clinical study, lung adenocarcinoma patients with high expression of CD274 (PD-L1; >/= 50%) and a co-occurring STK11 mutation demonstrated a similar objective response rate (P=0.2), progression-free survival (P=0.29), and overall survival (0.44) compared to patients with negative expression of CD274 (PD-L1) and a co-occurring EGFR mutation when treated with an unspecified immune checkpoint inhibitor (PMID: 32178965).	32178965

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