Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer

Zhe Huang; Fang Wu; Qinqin Xu; Lianxi Song; Xiangyu Zhang; Zhan Wang; Li Deng; Yongchang Zhang; Liang Zeng; Nong Yang

doi:10.1097/CM9.0000000000002720

Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer

Chin Med J (Engl). 2023 Jun 20;136(12):1422-1429. doi: 10.1097/CM9.0000000000002720. Epub 2023 May 17.

Authors

Zhe Huang¹, Fang Wu², Qinqin Xu³, Lianxi Song^{1

4}, Xiangyu Zhang¹, Zhan Wang¹, Li Deng¹, Yongchang Zhang^{1

4}, Liang Zeng¹, Nong Yang^{1

2}

Affiliations

¹ Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
² Department of Pathology, Immuno-Oncology Laboratory, School of Basic Medicine, Central South University, Changsha, Hunan 410013, China.
³ Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining, Qinghai 810000, China.
⁴ Department of Medical Oncology, Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.

Abstract

Background: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.

Methods: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.

Results: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.

Conclusion: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.

Clinical trial registration: https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.

MeSH terms

Brain Neoplasms* / drug therapy
Brain Neoplasms* / genetics
Carcinoma, Non-Small-Cell Lung* / genetics
Humans
Immune Checkpoint Inhibitors / therapeutic use
Lung Neoplasms* / genetics
Retrospective Studies

Substances

Immune Checkpoint Inhibitors

Associated data

ClinicalTrials.gov/NCT05129202