Table 1:
Recent and Ongoing Trials in Prophylactic Cardioprotection Interventions in Breast Cancer Patients
| Trial Number | Cancer Treatment Exposure | Trial Treatment/ Intervention | Outcomes | Results |
|---|---|---|---|---|
| Cardioprotection Trials Evaluating Modifications in Cancer Therapy in Breast Cancer Patients Receiving Anthracyclines | ||||
| Meta-analysis of 11 randomized controlled trials (12) | Anthracyclines | Dexrazoxane versus placebo or standard of care | Symptomatic heart failure, asymptomatic LVEF decline by multigated radionuclide angiography (MUGA) or echocardiogram, chemotherapy response rate | Lower occurrence of heart failure with dexrazoxane, no difference in chemotherapy response rate |
| Meta-analysis of 55 randomized controlled trials (13) | Anthracyclines | Dexrazoxane versus standard of care, liposomal doxorubicin versus standard formulation doxorubicin, continuous versus bolus infusion | Symptomatic heart failure, asymptomatic LVEF decline by MUGA or echocardiogram | Lower occurrence of heart failure and asymptomatic LVEF decline with dexrazoxane, continuous infusion of doxorubicin, and liposomal doxorubicin |
| Meta-analysis of 7 randomized controlled trials (14) | Anthracyclines | Liposomal doxorubicin versus standard formulation doxorubicin, epirubicin versus doxorubicin | Symptomatic heart failure, asymptomatic LVEF decline by MUGA or echocardiogram | Lower occurrence of heart failure with liposomal doxorubicin |
| Meta-analysis of 9 randomized controlled trials (15) | Anthracyclines | Liposomal doxorubicin versus standard formulation doxorubicin | Symptomatic heart failure, reduction in LVEF | Lower occurrence of heart failure and LVEF reduction with liposomal doxorubicin |
| Cardioprotection Trials Evaluating Neurohormonal Antagonists in Breast Cancer Patients Receiving Anthracyclines | ||||
| NCT03265574: PROACT (21) | Anthracyclines | Enalapril versus standard of care | LVEF by echocardiogram, Troponin T | Ongoing |
| NCT02053974 (19) | Anthracyclines | Spironolactone versus placebo | LVEF and E/e’ by echocardiogram | Less LVEF reduction and less E/e’ increase with spironolactone |
| NCT01708798 (20) | Anthracyclines | Eplerenone versus placebo | Average e’ by echocardiogram | No difference in average e’, terminated for futility |
| Cardioprotection Trials Evaluating Beta-Blockers in Breast Cancer Patients Receiving Anthracyclines | ||||
| NCT01724450: CECCY (22) | Anthracyclines | Carvedilol versus placebo | LVEF and diastolic function by echocardiogram, troponin I | No difference in LVEF; carvedilol attenuated diastolic dysfunction and Troponin I elevation |
| Cardioprotection Trials Evaluating ACEI/ARBs and Beta-Blockers Singly or in Combination in Breast Cancer Patients Receiving Anthracyclines and/or Trastuzumab | ||||
| NCT01016886: MANTICORE (23) | Trastuzumab ± Anthracyclines | Perindopril or Bisoprolol versus placebo | Indexed LV volume and LVEF by cMRI | No difference in indexed LV volume with perindopril or bisoprolol; less LVEF reduction with bisoprolol |
| NCT01434134: PRADA (24) | Anthracyclines ± Trastuzumab | Candesartan, Metoprolol, Candesartan +Metoprolol, versus placebo | LVEF by echocardiogram, biomarkers: troponin I and T, NTproBNP, BNP, c-reactive protein, galectin 3 | Less LVEF reduction with candesartan treatment, metoprolol attenuated troponin |
| NCT01009918 (26) | Trastuzumab ± Anthracyclines | Lisinopril or Carvedilol versus placebo | LVEF by echocardiogram | Less LVEF reduction with either lisinopril or carvedilol only in patients treated with combination trastuzumab plus doxorubicin |
| NCT00459771 (27) | Trastuzumab + Anthracyclines | Candesartan versus placebo | LVEF by echocardiogram, troponin T, BNP | No difference in LVEF, troponin T, or BNP with candesartan treatment |
| Cardioprotection Trials Evaluating Statins in Breast Cancer Patients Receiving Anthracyclines and/or Trastuzumab | ||||
| NCT01988571: PREVENT (28) | Anthracyclines | Atorvastatin versus placebo | LVEF by cMRI | Ongoing |
| NCT02096588 (29) | Anthracyclines ± Trastuzumab | Simvastatin versus standard of care | Global longitudinal strain by echocardiogram | Ongoing |
| Cardioprotection Trials Evaluating Beta-Blockers in Metastatic Her2-Positive Breast Cancer Patients | ||||
| NCT03418961: SWOG S1501 (30) | Trastuzumab | Carvedilol versus placebo | LVEF by echocardiogram, death, time to first cardiac event | Ongoing |
| Cardioprotection Trials Evaluating Radiation Therapy in Breast Cancer Patients | ||||
| NCT02603341: PCORI/RADCOMP (31) | ± adjuvant/ neoadjuvant chemotherapy | Proton versus photon radiation therapy | Cardiovascular and cancer mortality, quality of life | Ongoing |
| Cardioprotection Trials Evaluating Risk-Guided Strategies Using Imaging or Biomarkers in Breast Cancer Patients | ||||
| NCT01968200: ICOS-One (36) | Anthracyclines | Prophlyactic enalapril vs troponin-triggered enalapril | Troponin (various assay platforms), LVEF by echocardiogram | No difference in troponin elevation or LVEF between the preventive versus troponin-triggered initiation of enalapril treatment |
| EudraCT 2017-000896-99, ISRCTN 24439460: Cardiac-CARE (37) | Anthracyclines | Troponin-triggered ARB + beta-blocker versus standard of care | LVEF by cMRI, heart failure hospitalization | Ongoing |
| ACTRN12614000341628: SUCCOUR (41) | Anthracyclines and/or Trastuzumab | Global longitudinal strain-guided versus LVEF-guided ramipril and carvedilol | 3D LVEF by echocardiogram | Ongoing |