Differential organ-specific tumor response to first-line immune checkpoint inhibitor therapy in non-small cell lung cancer-a retrospective cohort study

Qi Wang; Yujia Fang; Chunyu Li; Tracy L Leong; Mariano Provencio; In-Jae Oh; Zhemin Zhang; Chunxia Su

doi:10.21037/tlcr-23-83

Differential organ-specific tumor response to first-line immune checkpoint inhibitor therapy in non-small cell lung cancer-a retrospective cohort study

Transl Lung Cancer Res. 2023 Feb 28;12(2):312-321. doi: 10.21037/tlcr-23-83. Epub 2023 Feb 25.

Authors

Qi Wang^#¹, Yujia Fang^#², Chunyu Li³, Tracy L Leong⁴, Mariano Provencio⁵, In-Jae Oh⁶, Zhemin Zhang⁷, Chunxia Su¹

Affiliations

¹ Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China.
² Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China.
³ Department of Integrated Chinese Traditional and Western Medicine, International Medical School, Tianjin Medical University, Tianjin, China.
⁴ Department of Respiratory Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
⁵ Medical Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
⁶ Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Jeonnam, Republic of Korea.
⁷ Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China.

^# Contributed equally.

Abstract

Background: Immune checkpoint inhibitors (ICIs) possess remarkable clinical effectiveness in non-small cell lung cancer (NSCLC). Different immune profiles of tumors may play a key role in the efficacy of treatment with ICIs. This article aimed to determine the differential organ responses to ICI in individuals with metastatic NSCLC.

Methods: This research analyzed data of advanced NSCLC patients receiving first-line treatment with ICIs. Major organs such as the liver, lung, adrenal glands, lymph nodes and brain were assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and RECIST-improved organ-specific response criteria.

Results: A retrospective analysis was conducted on a total of 105 individuals with advanced NSCLC with programmed death ligand-1 (PD-L1) expression ≥50% who received single agent anti-programmed cell death protein 1 (PD-1)/PD-L1 monoclonal antibodies as first-line therapy. Overall, 105 (100%), 17 (16.2%), 15 (14.3%), 13 (12.4%), and 45 (42.8%) individuals showed measurable lung tumors and liver, brain, adrenal, and other lymph node metastases at baseline. The median size of the lung, liver, brain, adrenal gland, and lymph nodes were 3.4, 3.1, 2.8, 1.9, and 1.8 cm, respectively. The results recorded mean response times of 2.1, 3.4, 2.5, 3.1, and 2.3 months, respectively. Organ-specific overall response rates (ORRs) were 67%, 30.6%, 34%, 39%, and 59.1%, respectively, with the liver having the lowest remission rate and lung lesions having the highest remission rate. There were 17 NSCLC patients with liver metastasis at baseline, and 6 had different responses to ICI treatment, with remission in the primary lung site and progressive disease (PD) in the metastatic liver site. At baseline, the mean progression-free survival (PFS) of the 17 patients with liver metastasis and 88 patients without liver metastasis was 4.3 and 7 months, respectively (P=0.02, 95% CI: 0.691 to 3.033).

Conclusions: The liver metastases of NSCLC may be less responsive to ICIs than other organs. The lymph nodes respond most favorably to ICIs. Further strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

Keywords: Lung cancer; immune checkpoint inhibitor (ICI); organ-specific response rates (OSRRs); tumor microenvironment (TME); tumor response.