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. 2025 Jun 23:16:1618110.
doi: 10.3389/fimmu.2025.1618110. eCollection 2025.

BRICS sequential therapeutic regimen as first-Line treatment for PD-L1-negative metastatic non-small cell lung cancer patients harboring EGFR/ALK wild-type status: a retrospective study

Jianxin Chen #  1 , Jian Wang #  2   1 , Weiqiang Fang  3 , Yating Wu  3 , Hang Li  3 , Hui Xu  3 , Yunyun Zhu  3 , Yanran Cheng  3 , Zongyang Yu  3 , Yonghai Peng  3
Affiliations

BRICS sequential therapeutic regimen as first-Line treatment for PD-L1-negative metastatic non-small cell lung cancer patients harboring EGFR/ALK wild-type status: a retrospective study

Jianxin Chen et al. Front Immunol. .

Abstract

Background: Patients with PD-L1-negative, EGFR/ALK wild-type metastatic non-small cell lung cancer (NSCLC) exhibit limited responses to immune checkpoint inhibitors (ICIs). This study evaluates the BRICS regimen-a sequential approach combining stereotactic body radiotherapy (SBRT), probiotics, PD-1 inhibitors, and low-dose chemotherapy-to overcome immunotherapy resistance.

Methods: This retrospective study included 23 patients treated between 2018 to 2024. Eligibility criteria: confirmed PD-L1-negative NSCLC, no actionable mutations, and measurable lesions. The BRICS regimen comprised SBRT (24 Gy in 3 fractions) to a single lesion, oral probiotics (6 g/day), low-dose chemotherapy, and PD-1 inhibitors administered every 21 days for six cycles. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results: Median age was 62 years; 82.6% were male. ORR and DCR were both 95.7%. Median PFS was 16 months (95% CI: 9.11-22.89), and median OS was 32.7 months (95% CI: 11.53-53.87). In subgroup analysis based on prior treatment status, median PFS and OS were numerically longer in treatment-naïve patients compared to previously treated patients (mPFS: 20.0 vs. 13.6 months; mOS: 48.0 vs. 18.0 months), though without statistical significance (P > 0.05). Poor ECOG performance status predicted poorer PFS (HR=9.908, p=0.013) and OS (HR=26.406, p=0.008). Adverse events were predominantly grade 1 to 2 (fatigue:13.2%, rash:8.7%), with no grade ≥3 toxicities.

Conclusions: The BRICS regimen demonstrated promising efficacy and safety in PD-L1-negative NSCLC, potentially overcoming resistance through multimodal immunomodulation. clinical benefit was observed regardless of treatment line, with a trend toward improved outcomes when administered as first-line therapy. Prospective trials are warranted to validate these findings and explore mechanisms underlying radiotherapy-microbiome-chemotherapy synergy.

Keywords: BRICS regimen; NSCLC; efficacy; first-line treatment; retrospective study.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Treatment protocol of BRICS sequential therapeutic regimen.
Figure 2
Figure 2
Kaplan-Meier survival curves of PFS in 23 patients.
Figure 3
Figure 3
Kaplan-Meier survival curves of OS in 23 patients.
Figure 4
Figure 4
Kaplan–Meier survival curves of PFS stratified by treatment history.
Figure 5
Figure 5
Kaplan–Meier survival curves of OS stratified by treatment history.
Figure 6
Figure 6
Univariate analysis of prognostic factors for PFS.
Figure 7
Figure 7
Univariate analysis of prognostic factors for OS.
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