Effect of proprotein convertase subtilisin/kexin type 9 inhibition on cancer events: A pooled, post hoc, competing risk analysis of alirocumab clinical trials

Cancer Med. 2023 Aug;12(16):16859-16868. doi: 10.1002/cam4.6310. Epub 2023 Jul 17.

Abstract

Objective: Assess the risk of new and worsening cancer events among participants who received the lipid-lowering therapy alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor.

Design: Pooled post hoc analysis.

Setting: Six phase 3 or phase 4 placebo-controlled randomised trials with alirocumab.

Participants: A total of 24,070 patients from the safety population with complete dosing data (alirocumab, n = 12,533; placebo, n = 11,537).

Intervention: Alirocumab 75 mg, alirocumab 150 mg, alirocumab 75 mg increasing to 150 mg if low-density lipoprotein cholesterol <50 mg/dL not achieved, or placebo, all every 2 weeks. All participants received background high-intensity or maximum-tolerated statin therapy.

Outcomes and measures: The first new or worsening incident cancer events were assessed during the treatment-emergent adverse event period. Four outcomes were evaluated: any-neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancers, and stricter definition of hormone-sensitive cancers. Sub-distribution hazard ratios and 95% confidence intervals (CIs) were estimated using a competing risk framework, with death as a competing risk.

Results: Considering both treatment arms in aggregate, 969 (4.03%), 779 (3.24%), 178 (0.74%) and 167 (0.69%) patients developed any neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancer and strict definition of hormone-sensitive cancer events, respectively. There was no significant difference in the risk of having any neoplasm in the alirocumab versus the placebo group (sub-distribution hazards ratio [95% CI], 0.93 [0.82-1.1]; p = 0.28). A nominally lower risk of having any neoplasms with alirocumab was observed among subjects aged ≥64 years (sub-distribution hazards ratio 0.83; 95% CI, 0.70-0.99).

Conclusions: Intensive low-density lipoprotein cholesterol lowering with a proprotein convertase subtilisin/kexin type 9 inhibitor combined with statin does not appear to increase the risk of new or worsening cancer events.

Keywords: LDL-C; PCSK9 inhibitor; alirocumab; cholesterol; incident cancer; serum lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal* / therapeutic use
  • Cholesterol, LDL
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Neoplasms* / drug therapy
  • Neoplasms* / epidemiology
  • PCSK9 Inhibitors* / adverse effects
  • PCSK9 Inhibitors* / therapeutic use
  • Risk Assessment
  • Subtilisins
  • Treatment Outcome

Substances

  • alirocumab
  • Antibodies, Monoclonal
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Subtilisins
  • PCSK9 Inhibitors