Background The majority of advanced non-small cell lung cancer (NSCLC) patients derives modest benefit from immunotherapy (IO) alone. For some of them, adding chemotherapy (CT) may significantly improve the outcomes, but the reliability of PD-L1 expression as the only biomarker to identify patients that might need concomitant CT is unsatisfactory.^1,2

Methods A systematic research of articles using PubMed/MEDLINE, and the Cochrane Database of Systematic Reviews and Central Register of Controlled Trials was performed, last updated April 11th, 2022. Abstract from main oncology congresses were also searched, including ASCO 2022. Eligible studies were randomized controlled clinical trials (RCT) investigating IO, alone or combined with CT, versus CT alone in previously untreated advanced NSCLC patients. The objective was to detect clinicopathological and molecular predictive factors of survival (progression-free survival and overall survival). Study characteristics and outcome estimates (hazard ratio and 95% CI) were extracted. Random-effects meta-analyses were performed to investigate IO alone versus CT, and IO plus CT versus CT. Random-effects meta-regression analyses were performed to provide a comparison of IO alone versus IO plus CT.

Results a total of 14367 patients with advanced NSCLC in 25 RCT was included (table 1).^3-48 Squamous histology, male gender, current/former smoker status, PD-L1 expression >=50%, and high TMB correlated with improved survival with IO alone compared to CT. Conversely, female gender, absence of smoking history, negative PD-L1 expression, and low TMB correlated with unsatisfactory outcomes with IO alone versus CT (figure 1), but not with IO plus CT versus CT (figure 2). IO plus CT improved survival versus IO alone in female patients [HR for PFS: 1.65, 95% CI, 1.25-2.18, p=0.0004; HR for OS: 1.31, 95% CI, 1.01-1.71, p=0.044], never smokers [HR for PFS: 3.59, 95% CI, 1.62-7.94, p=0.0016; HR for OS: 1.28, 95% CI, 0.95-1.72, p=0.10], in those having a PD-L1 expression >=1% [HR for PFS: 1.88, 95% CI, 1.55-2.28, p<0.0001; HR for OS: 1.28, 95% CI, 1.11-1.48, p=0.0007] or a low TMB [HR for PFS: 2.08, 95% CI, 1.61-2.70, p <0.0001; HR for OS: 1.43, 95% CI, 1.12-1.82, p=0.004], and in patients with central nervous system metastasis [HR for PFS: 1.51, 95% CI, 1.01-2.25, p=0.045; HR for OS: 1.32, 95% CI, 0.85-2.06, p=0.22] (figure 3).

Conclusions Certain clinicopathological and molecular features may add predictive value to PD-L1 expression in the selection of the most appropriate first-line treatment for advanced NSCLC patients.

References

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Abstract 800 Figure 1

IO versus CTGraphical representation of the PFS (A) and OS (B) of patients treated with IO versus CT resulting from the meta-analysis in each group.PFS: progression-free survival; OS: overall survival; IO: immunotherapy; CT: chemotherapy; CNS: central nervous system; PD-L1: programmed death-ligand 1; ECOG PS: eastern cooperative group performance status; TMB: tumor mutation burden.

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Abstract 800 Figure 2

IO plus CT versus CTGraphical representation of the PFS (A) and OS (B) of patients treated with IO plus CT versus CT resulting from the meta-analysis in each group.PFS: progression-free survival; OS: overall survival; IO: immunotherapy; CT: chemotherapy; CNS: central nervous system; PD-L1: programmed death-ligand 1; ECOG PS: eastern cooperative group performance status; TMB: tumor mutation burden.

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Abstract 800 Figure 3

. IO versus IO plus CTGraphical representation of the PFS (A) and OS (B) of patients treated with IO versus IO plus CT resulting from the meta-regression analysis in each group.PFS: progression-free survival; OS: overall survival; IO: immunotherapy; CT: chemotherapy; CNS: central nervous system; PD-L1: programmed death-ligand 1; ECOG PS: eastern cooperative group performance status; TMB: tumor mutation burden.