The association of tumor burden and anti-PD-1 inhibitor therapy efficacy in patients with untreated advanced non-small cell lung cancer.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16812
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kindai University
• Principal Investigator: HARATANI KOJI 近畿大学, 大学病院, 助教 (90760447)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 非小細胞肺癌 / 免疫治療 / 腫瘍免疫 / チェックポイント阻害薬 / PD-1 / 耐性 / 腫瘍量 / 遺伝子発現

Outline of Final Research Achievements

In this multi-institutional study, patients with treatment-naive metastatic non-small cell lung cancer (NSCLC) who received anti-PD-1 monotherapy (ICI-cohort, N=106), platinum-doublet therapy (Chemo-cohort, N=105), or anti-PD-1 with platinum-doublet therapy (ICI+Chemo-cohort, N=49) as their first-line treatment regimens were included to evaluate the association of tumor burden (TB) with treatment efficacy. This analysis showed significant association of high tumor burden with poor treatment efficacy only in ICI-cohort. Gene expression analysis of pretreatment tumor tissue from approximately 50 patients revealed that high tumor burden was associated with immunosuppressive phenotypes. Thus, this study suggested that high TB was associated with resistance to anti-PD-1 therapy in treatment-naive advanced NSCLC, possibly due to certain immunosuppressive phenotypes.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

治療前腫瘍量が多い未治療進行再発非小細胞肺癌においては、PD-1阻害薬単独治療では治療効果が不十分であることがわかった一方、殺細胞薬などを適切に併用することでそれを克服できる可能性が示唆された。また、免疫関連遺伝子発現解析により、腫瘍量が多い場合に特定の免疫プロファイルによってPD-1阻害薬単独治療への耐性を示すことが示唆された。これらの知見によって、腫瘍量の大小による治療戦略の最適化が促進すことが期待される。