6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial

Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium

“…Patients with Stage 1 or 2, HER2 + BCs may consider ado-trastuzumab emtansine (± pertuzumab) with comparable efficacy to chemotherapy/trastuzumab-based regimens in either neoadjuvant or adjuvant settings (Priority B2) to minimize neutropenia, visits, and steroid-use [30,31]. Adjuvant trastuzumab-based therapy may be shortened from 12 to 6 months without affecting outcomes in selected patients (Priority B3) [32,33].…”

Enhancing global access to cancer medicines

“…The larger, phase 3 PHARE (Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure) and PERSEPHONE (6 versus 12 months of adjuvant trastuzumab for HER2‐positive early breast cancer) trials in HER2‐positive, early breast cancer had similar designs and assessed the same clinical endpoints . The final PHARE analysis, with a median follow‐up of 7.5 years, failed to show that 6 months of trastuzumab was noninferior to 12 months of trastuzumab; the frequency of cardiac events was lower in the 6‐month arm.…”

“…Pharmaceutical companies are not typically interested in sponsoring trials for neglected cancers (eg, liver, brain) or for investigating de‐escalation of established cancer medicines that are no longer under patent . PHARE (described above) was funded by the French National Cancer Institute, whereas the International Duration of Evaluation of Adjuvant Therapy (IDEA) analysis of colon cancer was funded by various noncommercial grants …”

“…79 PHARE (described above) was funded by the French National Cancer Institute, whereas the International Duration of Evaluation of Adjuvant Therapy (IDEA) analysis of colon cancer was funded by various noncommercial grants. 69,80 Although participation in commercial clinical trials provides middle-income countries access to biomarkers and to standard and investigational drugs, which might not otherwise be available, the trials might not always address the health priorities of these countries, and access might stop on trial completion.…”

Is the duration of adjuvant trastuzumab debate still clinically relevant?

“…In the past decade, multiple trials, including two phase 3 randomised trials, 7,8 one three-group phase 2 trial, 2 and two single-group phase 2 trials, 9,10 have found an excellent therapeutic index associated with novel, anthracycline-free regimens. Additionally, five studies [11][12][13][14][15][16] evaluated whether a shorter duration of trastuzumab is non-inferior to the standard year. Non-inferiority could not be concluded in the first four studies; [11][12][13][14] thus, the debate appeared to be closed.…”