The Application of Combined Immune Checkpoint Inhibitor Modalities in Previously Treated Non-Small Cell Lung Cancer Patients and the Associations Thereof With the Lung Immune Prognostic Index

Ting Zhang; Xue Yang; Jing Zhao; Lixia Xia; Qiyuan Wang; Rui Jin; Lingxiao Zhou; Bin Zhang; Jun Zhao; Huijie Li; Wen Li; Yang Xia

doi:10.3389/fonc.2021.690093

The Application of Combined Immune Checkpoint Inhibitor Modalities in Previously Treated Non-Small Cell Lung Cancer Patients and the Associations Thereof With the Lung Immune Prognostic Index

Front Oncol. 2021 Jun 4:11:690093. doi: 10.3389/fonc.2021.690093. eCollection 2021.

Authors

Ting Zhang¹, Xue Yang², Jing Zhao³, Lixia Xia⁴, Qiyuan Wang⁵, Rui Jin⁴, Lingxiao Zhou⁴, Bin Zhang⁴, Jun Zhao², Huijie Li⁶, Wen Li⁴, Yang Xia⁴

Affiliations

¹ Department of Radiation Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
³ Department of Medical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁴ Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁵ Department of Radiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁶ Department of Medical Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

Abstract

Background: Immune checkpoint inhibitor (ICI) monotherapy remains the standard of care for patients with previously treated non-small cell lung cancer. However, few reports have compared the clinical benefits of second-line ICIs alone with those of ICIs combined with other therapies, including anti-angiogenesis therapy or chemotherapy.

Methods: Patients with previously treated advanced non-small cell lung cancer who received ICIs were retrospectively reviewed. The progression-free survival (PFS), overall survival, objective response rate, disease control rate, and safety were assessed. Complete blood cell counts and serum lactate dehydrogenase (LDH) levels were measured before and after ICI treatment.

Results: Of 120 patients, 75 were treated with ICI monotherapy, 26 with ICIs plus anti-angiogenic therapy (ICI+A), and 19 with ICIs plus chemotherapy (ICI+C). The objective response rate was significantly higher in the ICI+C group (57.9%) than ICI monotherapy (26.3%) and ICI+A (31.8%) groups. The depth of response was significantly greater in the ICI+C (-35.1%) than ICI+A (-2.04%) and ICI monotherapy (3.963%) groups. ICI+C afforded a better PFS compared with the ICI monotherapy and ICI+A groups (8.5 vs. 4.6 and 4.1 months, respectively). Notably, the pre- and post-treatment peripheral neutrophil/lymphocyte ratios and serum LDH levels were negatively correlated with the PFS of the entire cohort. More importantly, the pretreatment lung immune prognostic index (neutrophil/lymphocyte ratio ≥ 4 and LDH level ≥ upper limit of normal) satisfactorily predicted the responses to ICI-based strategies. Adverse events (AEs) occurred in 65.3%, 92.3%, and 94.7% of patients in the ICI monotherapy, ICI+A, and ICI+C groups, respectively. Grade 3-5 AEs were more common in the combination therapy groups (ICI+A, 19.2%; ICI+C, 21%; ICI monotherapy, 4%).

Conclusion: In second-line settings and beyond, ICIs combined with chemotherapy prolonged survival, with tolerable AEs. Addition of anti-angiogenic agents to ICIs did not afford any additional benefits. Further prospective studies are warranted.

Keywords: anti-angiogenic therapy; chemotherapy; immune checkpoint inhibitor (ICI); lung immune prognostic index (LIPI); non-small cell lung cancer (NSCLC).