Researchers say they have identified factors associated with survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy or immunochemotherapy.

Factors such as histology, sex, smoking status, PD-L1 expression, and tumor mutational burden (TMB) were associated with progression-free survival (PFS) and overall survival (OS) outcomes in NSCLC patients who received immunotherapy alone or in combination with chemotherapy.

These findings, from a meta-analysis, were published in the Journal of the National Cancer Institute.

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The meta-analysis included 25 randomized controlled trials and a total of 14,367 patients with advanced, previously untreated NSCLC. The patients were treated with a PD-L1 inhibitor alone, a PD-L1 inhibitor plus a CTLA-4 inhibitor and/or platinum-based chemotherapy, or platinum-based chemotherapy alone. 

Immunotherapy vs Chemotherapy

When compared with chemotherapy alone, immunotherapy significantly improved PFS (hazard ratio [HR], 0.81; 95% CI, 0.67-0.99; P =.04) and OS (HR, 0.78; 95% CI, 0.69-0.87; P <.001). The greatest improvements were seen in:

  • Patients with squamous histology (HR for PFS, 0.60, 95% CI, 0.44-0.81, P =.001; HR for OS, 0.70, 95% CI, 0.61-0.79, P <.001)
  • Men (HR for PFS, 0.60, 95% CI, 0.33-1.07, P =.08; HR for OS, 0.70, 95% CI, 0.59-0.82, P <.001 )
  • Current or former smokers (HR for PFS, 0.68, 95% CI, 0.40-1.15, P =.15; HR for OS, 0.73, 95% CI, 0.62-0.85, P <.001)
  • Patients with PD-L1 expression of 50% or higher (HR for PFS, 0.68, 95% CI, 0.54-0.84, P <.001; HR for OS, 0.70, 95% CI, 0.64-0.77, P <.001)
  • Patients with high TMB (HR for PFS, 0.69, 95% CI, 0.60-0.79, P <.001; HR for OS, 0.68, 95% CI 0.59-0.77, P <.001). 

Immunotherapy was associated with survival improvements regardless of central nervous system (CNS) metastasis or mutations in KRAS, STK11, or KEAP1.

Immunochemotherapy vs Chemotherapy Alone

When compared with chemotherapy alone, immunotherapy plus chemotherapy was associated with significantly improved PFS (HR, 0.58; 95% CI, 0.54-0.63; P <.001) and OS (HR, 0.74; 95% CI, 0.69-0.79; P <.001). These improvements were seen across all subgroups, including among:

  • Women (HR for PFS, 0.61, 95% CI, 0.53-0.69, P <.001; HR for OS, 0.68, 95% CI, 0.56-0.83, P <.001)
  • Never smokers (HR for PFS, 0.62, 95% CI, 0.49-0.77, P <.001; HR for OS, 0.73, 95% CI, 0.60-0.89, P =.002)
  • Patients with PD-L1 expression below 1% (HR for PFS, 0.65, 95% CI, 0.58-0.73, P <.001; HR for OS, 0.76, 95% CI, 0.69-0.83, P <.001) 
  • Patients with low TMB (HR for PFS, 0.65, 95% CI, 0.55-0.78, P <.001; HR for OS, 0.73, 95% CI, 0.61-0.88, P <.001). 

The researchers noted that combination immunotherapy and chemotherapy improved outcomes regardless of histology; age; ECOG performance status; the presence of mutations in KRAS, STK11, or KEAP1; or the presence of liver or brain metastasis. 

In fact, patients with CNS metastasis appeared to derive the greatest benefit from immunotherapy-chemotherapy (HR for PFS, 0.44, 95% CI, 0.36-0.55, P <.001; HR for OS, 0.46, 95% CI, 0.36-0.59, P <.001).

Immunotherapy Alone vs Immunochemotherapy

Compared with immunotherapy alone, immunotherapy plus chemotherapy was associated with significantly improved PFS (HR, 1.42; 1.19-1.69, P <.001). However, there was no significant difference in OS between the groups (HR, 1.06, 0.94-1.20, P =.36). 

Immunotherapy plus chemotherapy was associated with a significant improvement in PFS among:

  • Women (HR, 1.65; 95% CI, 1.25-2.18; P <.001)
  • Patients with non-squamous histology (HR, 1.37; 95% CI, 1.10-1.70; P =.005)
  • Never smokers (HR, 3.59; 95% CI, 1.62-7.94; P =.002)
  • Patients with CNS metastasis (HR, 1.51; 95% CI, 1.01-2.25; P =.045)
  • Patients with PD-L1 expression of 1% or higher (HR, 1.79; 95% CI, 1.47-2.18; P <.001)
  • Patients with low TMB (HR for PFS, 2.08, 95% CI, 1.61-2.70, P <.001).

A significant OS benefit with immunotherapy plus chemotherapy was seen for:

  • Women (HR, 1.31; 95% CI, 1.01-1.71; P =.044)
  • Patients with PD-L1 expression of 1% or higher (HR, 1.24; 95% CI, 1.09-1.40; P =.001) 
  • Patients with low TMB (HR, 1.43; 95% CI, 1.12-1.82; P =.004). 

“Several clinicopathological and molecular features, such as sex, smoking status, CNS metastatic site, and TMB represent possible predictors of IO [immunotherapy] efficacy that, in the absence of specific randomized comparative trials, can be added to PD-L1 expression to guide thoracic oncologists in the choice between IO alone or combined with CT [chemotherapy],” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Di Federico A, De Giglio A, Gelsomino F, et al. Predictors of survival to immunotherapy and chemoimmunotherapy in non-small cell lung cancer: A meta-analysis. J Natl Cancer Inst. Published online November 2, 2022. doi:10.1093/jnci/djac205

Topics:

Lung Cancer Non-Small Cell Lung Cancer