Subtle Differences in NSCLC Could Help Guide Treatment Strategies

Although immunotherapy has become central to first-line treatment for non–small cell lung cancer (NSCLC), a recent study, highlighting squamous cell and non–squamous cell histology, suggests subtle differences in patient populations may be important in caring for patients in some NSCLC subgroups.

Study findings were published in Cancer Management and Research.

Since 2015, when the FDA approved nivolumab for treating metastatic NSCLC, immune checkpoint blockade has become a cornerstone of first-line treatment, particularly in the forms of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and anti-cytotoxic T-lymphocyte–associated protein 4 (CTLA4), the authors wrote.

“Across all stages of NSCLC, immunotherapy has demonstrated its efficacy and become a major part of standard care,” the authors said.

In the present study, researchers sought to better understand cemiplimab-rwlc, a monoclonal antibody that works against programmed cell death. It was the third PD-1/PD-L1 inhibitor to be approved for first-line treatment in NSCLC, given as monotherapy or in combination with chemotherapy.

In conducting this review, they focused on subtle differences in patient populations for the cemiplimab studies, EMPOWER-Lung 1 and EMPOWER Lung-3, considering primary and subgroup results.  

EMPOWER-Lung 1: Patients received cemiplimab monotherapy or chemotherapy. Based on study data, the FDA approved cemiplimab in February 2021 as first-line monotherapy for patients with advanced NSCLC with PD-L1 expression of at least 50% that was otherwise negative for EGFR, ALK, or ROS1 aberrations.

Three-year follow-up data were presented at the 2022 European Lung Cancer Congress (ELCC). Data included several subgroup analyses: 

• In patients with locally advanced NSCLC, largely excluded in prior immunotherapy trials, the cemiplimab group had a median overall survival (OS) of 26.1 months vs 13.9 months in the chemotherapy group (HR, 0.67; CI 95%, 0.38-1.17)
• In patients with treated, clinically stable brain metastases at baseline, progression-free survival (PFS) was 12.5 months in the cemiplimab group vs 5.3 months in the chemotherapy group (HR, 0.34; 95% CI, 0.18-0.63).

EMPOWER-Lung 3: Patients received cemiplimab plus chemotherapy or chemotherapy with placebo. Unlike most other chemotherapy and immunology trials, EMPOWER-Lung 3 enrolled patients irrespective of histology. Moreover, the trial included patients with stage IIIB/IIIC disease who were not candidates for definitive chemoradiation therapy. The cemiplimab-plus-chemotherapy group had a median OS of 21.9 months (95% CI, 15.5-NE) vs 13.0 months (95% CI, 11.9-16.1) in the chemotherapy-plus-placebo group (HR, 0.71; 95% CI, 0.53-0.93; P = .014).

Based on study data, in November 2022, the FDA approved cemiplimab in combination with platinum-based therapy for first-line treatment of adult patients with advanced NSCLC and no EGFR, ALK, or ROS1 aberrations, regardless of PD-L1 expression.

Two-year follow-up of the EMPOWER-Lung 3 study was presented at ELCC 2023. Overall, cemiplimab plus chemotherapy showed an improvement in survival, with a median OS of 21.1 months vs 12.9 months for chemotherapy with placebo (HR, 0.65; 95% CI, 0.51-0.82; P = .0003).

In a comparison by histology type, data showed the following:

• Squamous cell histology group:
  • Median OS in the chemotherapy-plus-cemiplimab group was 22.3 months
  • Median OS in the chemotherapy-plus-placebo group was 13.8 months (HR, 0.61; 95% CI, 0.42-0.87)
  • Median PFS in the chemotherapy-plus-cemiplimab group was 8.2 months
  • Median PFS in the chemotherapy-plus-placebo group was 4.9 months (HR, 0.49; 95% CI, 0.41-0.59)

• Non–squamous cell histology group:
  • Median OS in the chemotherapy-plus-cemiplimab group was 19.4 months
  • Median OS in the chemotherapy-plus-placebo group was 12.4 months (HR, 0.64; 95% C,I 0.47-0.88).
  • Median PFS in the chemotherapy-plus-cemiplimab group was 7.9 months
  • Median PFS in the chemotherapy-plus-placebo group was 5.7 months (HR, 0.53; 95% CI, 0.39-0.71).

Although the EMPOWER-Lung 3 subgroup analysis was not statistically powered, the cemiplimab-and-chemotherapy group demonstrated better results for PFS and OS in squamous histology compared with nonsquamous histology, the researchers said.

In addition, they compared NSCLC trials that used different immunotherapy agents (atezolizumab and pembrolizumab), looking at the squamous cell histology group. Although it is difficult to make a “head-to-head comparison between trials,” they noted, cemiplimab and chemotherapy appears to have better OS (22.3 vs 17.1 months) compared with the pembrolizumab-plus-chemotherapy group.

“Tumor histology appears to play an important role in determining efficacy of immunotherapy in combination with chemotherapy,” the authors concluded. “While it may not meet an ‘unmet need,’ the addition of another option for immunotherapy in NSCLC, as monotherapy or in combination with chemotherapy, may help us to better manage patients in a more personalized way.”

Reference

Ahn J, Nagasaka M. Spotlight on cemiplimab-rwlc in the treatment of non-small cell lung cancer (NSCLC): focus on patient selection and considerations. Cancer Manag Res. 2023;15:627-634. doi:10.2147/CMAR.S325856