The prognostic factors of clinical outcomes in non-small cell lung cancer patients receiving subsequent treatments after progression on initial immunotherapy

Abstract

Background: The standard of care for non-small cell lung cancer (NSCLC) patients who encounter progression on initial immune checkpoint inhibitor (ICI) based treatment is uncertain. In the real world, there are various subsequent treatment options, but how to find the most suitable treatment for different patients is still unknown. The present study aimed to explore prognostic factors of subsequent treatment after progression (STAP) (defined as the next treatment after progression from the initial immunotherapy) of initial immunotherapy.

Methods: In this retrospective cohort study, NSCLC patients received regimens after progression of initial immunotherapy at Beijing Chest Hospital, Capital Medical University, between March 2016 and May 2023 were retrieved. The major efficacy endpoint was progression-free survival 2 (PFS2), defined as the time from the initiation of next treatment after initial immunotherapy failure to disease progression or death from any cause. Subgroup analyses were conducted according to baseline characteristics, some subsequent regimens beyond progression, etc. for prognostic factors exploration. The Cox proportional hazards model was used for multivariate analysis.

Results: There were 176 patients enrolled. Median age was 64 years. There were 36 (20.5%) females, and 123 (69.9%) were smokers. Adenocarcinoma (99, 56.2%) was the major histological subtype. There were 95 (54.0%) patients with negative expression for programmed cell death ligand 1 (PD-L1). After progressive disease, 92 (52.3%) patients reused ICI-based treatment after progressive disease. Median PFS2 was 3.6 months [95% confidence interval (CI): 2.8-4.4]. Longer PFS2 was observed in patients with PD-L1 positive expression [hazard ratio (HR) =0.672, 95% CI: 0.477-0.947, P=0.023] or PFS ≥6 months in initial immunotherapy (HR =0.543, 95% CI: 0.358-0.824, P=0.004). Besides, patients switching to new ICI-based treatments without radiotherapy gained better PFS2 compared with patients receiving prior regimens (P=0.019).

Conclusions: PD-L1 positive expression, and longer PFS in initial immunotherapy would be good prognostic factors for NSCLC patients undergoing STAP on first immunotherapy. Besides, compared with original regimen, changing ICI would prolong PFS2 for NSCLC patients reusing ICI.

Keywords: Non-small cell lung cancer (NSCLC); immune checkpoint inhibitor (ICI); retreatment.

Figure 1

Flowchart of patient inclusion and exclusion. NSCLC, non-small cell lung cancer; ICI immune checkpoint inhibitor; irAE, immune-related adverse event.

Figure 2

Kaplan-Meier curves of PFS2 in patients with different baseline characteristics. (A) gender; (B) age [patients were divided into ≥65 years group (n=81) and <65 years group (n=95)]; (C) smoking status; (D) PD-L1 TPS (negative means PD-L1 expression <1%, positive means PD-L1 expression ≥1%), PD-L1 positive expression predicts a better PFS2 (P=0.0036); (E) treatment line; (F) histologic subtype (we only analysis the patients whose histologic subtype is adenocarcinoma or squamous cell carcinoma); (G) patients achieved PR of initial BOR have a longer PFS2 (P=0.024); (H) PFS1 <6 months predicts a worse PFS2 (P<0.0001); (I) PFS1 <3 months predicts a worse PFS2 (P=0.0013). PD-L1, programmed cell death ligand 1; TPS, tumor proportion score; ICI, immune checkpoint inhibitor; PFS1, progression-free survival of initial immunotherapy; m, months; BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease.

Figure 3

Univariate and multivariate analysis of progression-free survival 2. CI, confidence interval; PD-L1, programmed cell death ligand 1; PR, partial response; SD, stable disease; PD, progressive disease; PFS1, progression-free survival of initial immunotherapy; m, months.

Figure 4

Kaplan-Meier curves of progression-free survival 2 in patients with different systemic regimens after initial immunotherapy progression. (A) Survival curves for patients with and without ICI-based treatment; (B) survival curves for patients with and without ICI-based treatment, excluding patients receiving initial regimen; (C) survival curves for patients with initial regimen and non-immunotherapy; (D) survival curves for patients with initial regimen and patients receiving new regimen but still using original ICI; (E) survival curves for patients with new ICI and patients receiving new regimen but still using original ICI; (F) survival curves for patients with initial regimen and new ICI-based treatment; (G) survival curves for patients with new ICI-based treatment and initial regimen; (H) survival curves for patients receiving ICI with chemotherapy and patients receiving ICI with chemotherapy plus anti-angiogenic therapy. ICI, immune checkpoint inhibitor; chemo, chemotherapy; A, anti-angiogenic therapy.