Canakinumab improves survival in advanced NSCLC

Treatment with canakinumab appears beneficial to patients with advanced nonsmall cell lung cancer (NSCLC) with low T-cell infiltration (ie, low total count or immune desert phenotype), results of predefined exploratory biomarker analyses from the CANOPY-1 have shown.

“CANOPY-1 was a phase III study evaluating the efficacy and safety of pembrolizumab plus platinum-based doublet chemotherapy combined with canakinumab or placebo as first-line therapy for patients with NSCLC,” according to the investigators, led by Daniel S Tan from the National Cancer Centre, Duke-NUS Medical School in Singapore.

Tan presented the findings of the current study at the recent WCLC 2023 held in Singapore. He and his team carried out exploratory analyses to examine the prognostic role of CD8+ in patients treated with immune checkpoint inhibitors (ICI) and chemotherapy. They also assessed the effect of canakinumab in subgroups of patients defined by their CD8 count in tumour samples.

Specifically, Tan and colleagues used a CD8/panCK dual immunohistochemistry assay to quantify both the total CD8 count and the spatial localization of CD8+ cells in the tumour versus the stroma compartment based on a predefined algorithm. This resulted in the classification of baseline tumour samples according to three phenotypes, namely immune desert, excluded, and inflamed.

Using samples from 500 of the 643 patients enrolled in CANOPY-1, the investigators conducted two analyses of CD8 subgroups: total CD8 count in tumour samples (low vs high based on the median cutoff) and T-cell phenotype (immune desert vs excluded vs inflamed). They then assessed the prognostic and predictive roles of biomarkers using descriptive statistical comparisons and a Cox model.

Improved survival

Of the patients, 298 had available whole-transciptome data generated by RNAseq of baseline tumour samples. Regardless of treatment received, patients with high T-cell infiltration status (high total CD8 count or inflamed phenotype) achieved significant improvements in overall (OS) and progression-free survival (PFS). [WCLC 2023, abstract 1310]

Compared with placebo, canakinumab treatment in patients with a low total CD8 count resulted in improved median OS (17.1 vs 12.9 months; hazard ratio [HR], 0.722, 95 percent confidence interval [CI], 0.515‒1.010; p=0.134) and improved median PFS (6.7 vs 4.9 months; HR, 0.531, 95 percent CI, 0.363‒0.778; p<0.001).

Median PFS also got better in patients with an immune desert T-cell phenotype (compared with placebo: 6.9 vs 5.0 months; HR, 0.469, 95 percent CI, 0.216‒1.020; p=0.009), but median OS was not reached with canakinumab relative to 10.4 months with placebo (HR, 0.583, 95 percent CI, 0.311‒1.090; p=0.141).

In subgroups defined by total CD8 count and T-cell phenotype, no clinically relevant imbalances were observed in baseline characteristics between treatment groups.

Notably, “[t]ranscriptome analysis revealed that CD8-low/immune desert subgroups had higher suppressive myeloid tumour microenvironment features,” the investigators said.

“Preclinical studies and the neoadjuvant CANOPY-N trial recently showed that canakinumab combined with ICI could decrease immunosuppressive features and activate a CD8-driven antitumor response, providing potential rationale for the findings from CANOPY-1 subgroup analyses,” they said. [Mok TSK, et al, ESMO Asia 2022]