Anti-hypertensives associated with survival in cancer patients receiving immunotherapy: new evidence from a real-world cohort study and meta-analysis

Abstract

Background: The efficacy of immune checkpoint inhibitors (ICIs) in cancer patients taking anti-hypertensive drugs is still not well established.

Objective: To elucidate the effect of anti-hypertensive drugs on the clinical outcome of cancer patients receiving immunotherapy.

Design: A retrospective cohort study and meta-analysis.

Method: We conducted a real-world retrospective study of cancer patients treated with immunotherapy at two tertiary centers between January 2019 and June 2023, with primary outcomes being overall survival (OS) and progression-free survival (PFS). In addition, we performed a meta-analysis to synthesize currently relevant clinical studies.

Results: A retrospective clinical study of 336 patients from 2 centers suggested that the use of anti-hypertensive drugs was related to a preferable OS (hazard ratio (HR) = 0.55, 95% confidence interval (CI): 0.33-0.90) compared to non-users. For PFS, no significant correlation was detected (HR = 0.71, 95% CI: 0.49-1.03). Further analysis revealed that renin-angiotensin system inhibitor (RASi) and calcium channel blocker (CCB) have a synergistic effect with ICIs. In addition, subgroup analysis found that the benefits of RASi or CCB in combination with ICIs are greater in women or patients ⩾65 years of age. There was better disease control in lung cancer patients using RASi, and a significantly longer OS was observed in patients with gastrointestinal tumors taking CCB. Meta-analysis suggested that anti-hypertensive drugs were associated with improved OS, but only the combination of RASi and immunotherapy showed a synergistic effect. No significant correlation with OS was found for other anti-hypertensive drugs, and there was no overall positive effect on PFS.

Conclusion: Our study found that use of anti-hypertensive drugs, particularly RASi or CCB, was associated with improved OS in patients undergoing immunotherapy. The synergistic effects of RASi or CCB with ICIs were more pronounced in females or elderly. RASi or CCB exhibited different benefits in various types of tumors. These findings provide valuable insights for treating cancer patients with hypertension.

Keywords: anti-hypertensive drugs; calcium channel blocker; cancer survival; immune checkpoint inhibitors; renin–angiotensin system inhibitor.

Figure 1.

The relationship between anti-hypertensive drugs and immunotherapy. (a and b) Kaplan–Meier curves for the association of anti-hypertensive drug use with OS and PFS. (c and d) OS and PFS in RASi versus non-RASi patients. (e and f) OS and PFS in CCB versus non-CCB patients (after matched). CCB, calcium channel blocker; OS, overall survival; PFS, progression-free survival; RASi, renin–angiotensin system inhibitor.

Figure 2.

Subgroup analysis of the effect of RASi use on OS (a) and PFS (b) in patients receiving ICIs. Abbreviations: CI, confidence interval; ECOG-PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; ICIs, immune checkpoint inhibitors; OS, overall survival; PFS, progression-free; RASi, renin–angiotensin system inhibitor.

Figure 3.

Subgroup analysis of the effect of CCB use on OS (a) and PFS (b) in patients receiving ICIs. CCB, calcium channel blocker; CI, confidence interval; ECOG-PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; ICIs, immune checkpoint inhibitors; OS, overall survival; PFS, progression-free survival.

Figure 4.

PRISMA flow chart. Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analysis.

Figure 5.

Forest plots of the hazard ratio of OS in patients receiving immunotherapy combined with anti-hypertensive drugs. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; OS, overall survival; RASi, renin–angiotensin system inhibitor.

Figure 6.

Forest plots of the hazard ratio of PFS in patients receiving immunotherapy combined with anti-hypertensive drugs. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; RASi, renin–angiotensin system inhibitor.

Figure 7.

Forest plots of HR of OS in patients receiving ICIs combined with different anti-hypertensive drugs. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; OS, overall survival; RASi, renin–angiotensin system inhibitor.

Figure 8.

Forest plots of the HR of PFS in patients receiving ICIs combined with different anti-hypertensive drugs. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; ICIs, immune checkpoint inhibitors; PFS, progression-free survival; RASi, renin–angiotensin system inhibitor.

Figure 9.

Forest plots of the HR of OS with regard to cancer. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; mRCC, metastatic renal cell cancer; NSCLC, non-small-cell lung cancer; OS, overall survival; RASi, renin–angiotensin system inhibitor; UC, urothelium cancer.

Figure 10.

Forest plots of the HR of PFS with regard to cancer. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; mRCC, metastatic renal cell cancer; PFS, progression-free survival; RASi, renin–angiotensin system inhibitor.