Adding canakinumab to SoC confers no survival benefit in advanced NSCLC
10 May 2022
bởiRoshini Claire Anthony
The addition of the monoclonal anti-interleukin-1β antibody canakinumab to the standard of care (SoC) regimen of platinum doublet chemotherapy and pembrolizumab in the first-line setting did not improve progression-free survival (PFS) or overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC), results of the phase III CANOPY-1 trial showed.
Study participants were 643 patients (median age 63 years, 71–72 percent male) with previously untreated stage IIIB–IV NSCLC of any histology (69–70 percent with non-squamous histology), known PD-L1 status, ECOG performance status 0–1, and without EGFR and/or ALK alterations. They received four cycles of intravenous pembrolizumab and histology-guided platinum-based doublet chemotherapy Q3W and were randomized 1:1 to receive either subcutaneous canakinumab (200 mg) or placebo Q3W. This was followed by canakinumab or placebo (based on previous randomization) plus pembrolizumab with or without pemetrexed as maintenance.
About 91 percent of patients had stage IV disease at baseline. Eleven and nine percent of patients in the canakinumab and placebo groups, respectively, had brain metastases, 47 and 48 percent, respectively, had PD-L1 <1 percent, and 78 and 83 percent, respectively, were current/former smokers.
After a median follow-up of 4.8 months, PFS did not significantly differ between patients who received canakinumab or placebo (median 6.8 months in each group; hazard ratio [HR], 0.85, 95 percent confidence interval [CI], 0.67–1.09; pone-sided=0.102). [AACR 2022, abstract CT037]
OS was also not significantly different between patients who received canakinumab or placebo after a median follow-up of 16.2 months (median 20.8 vs 20.2 months; HR, 0.87, 95 percent CI, 0.70–1.10; pone-sided=0.123).
“We did not observe any significant biomarker subsets that especially benefitted from the addition of canakinumab,” said study author Dr Daniel Tan from the National Cancer Centre Singapore.
Overall response rate was comparable between the canakinumab and placebo arms (45.6 percent vs 45.5 percent), with disease control rates of 86.9 and 84.8 percent, respectively. One canakinumab and three placebo recipients achieved complete response, 45.3 and 44.6 percent, respectively, partial response, and 41.3 and 39.3 percent, respectively, had stable disease. Duration of response was a median 14.3 and 13.6 months, respectively.
Patient-reported outcomes based on EORTC QLQ-LC13* showed benefits with the addition of canakinumab vs placebo in terms of delaying time to deterioration of cough (median not evaluable [NE] vs 23.06 months; HR, 0.59; pone-sided=0.0007), chest pain (median NE vs 22.14 months; HR, 0.62; pone-sided=0.002), and dyspnoea (median 19.61 vs 11.50 months; HR, 0.66; pone-sided=0.0005).
Grade 3–4 adverse events (AEs) were reported in 64.1 and 59.3 percent of canakinumab and placebo recipients, respectively, with 57.2 and 51.9 percent, respectively, deemed treatment related. Twenty-four and 18.6 percent, respectively, experienced grade 3–4 treatment-related serious AEs. AEs led to discontinuation of any study drug in 22.5 and 18.9 percent of canakinumab and placebo recipients, respectively, and serious AEs led to death in 11.6 and 14.6 percent, respectively.
There were more dose adjustments and interruptions due to AEs in the canakinumab vs placebo arm, noted Tan.
The most common grade 3–4 AEs in the canakinumab vs placebo arms were anaemia (16.3 percent vs 20.5 percent), neutropenia (24.4 percent vs 16.8 percent), and decreased neutrophil count (13.4 percent vs 11.5 percent).
“No unexpected safety findings were observed with the addition of canakinumab to pembrolizumab plus platinum doublet chemotherapy,” said Tan.
Twenty-four and 22 percent of patients in the canakinumab and placebo arms, respectively, are still on treatment. The median duration of treatment was 8.7 and 7.9 months, respectively. The primary reason for treatment discontinuation was progressive disease (46.6 and 45.8 percent, respectively).
According to exploratory analysis, baseline high sensitivity C-reactive protein and interleukin 6 levels were prognostic factors with a decrease in levels noted in both study arms, but especially so with canakinumab, said Tan.