Deescalating Adjuvant Trastuzumab in HER2-Positive Early-Stage Breast Cancer: A Systemic Review and Meta-Analysis

Abstract

Background One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods A search of PubMed and abstracts from key conferences identified randomized trials that compared abbreviated trastuzumab therapy to 1 year of treatment in early-stage HER2-positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for disease-free survival (DFS) and overall survival (OS). Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor expression, and the duration of abbreviated trastuzumab (9–12 weeks vs 6 months). Odds ratios (ORs) and 95% confidence intervals were computed for prespecified cardiotoxicity events including cardiac dysfunction and congestive heart failure. P values were two-sided. Results Analysis included six trials comprising 11 603 patients. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI = 1.05 to 1.25, P = .002) and OS (HR = 1.15, 95% CI = 1.02 to 1.29. P = .02). The effect on DFS was not influenced by estrogen receptor status (P for the subgroup difference = .23), nodal involvement (P = .44), or the different duration of trastuzumab in the experimental arm (P = .09). Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI = 0.55 to 0.81, P < .001) and congestive heart failure (OR = 0.66, 95% CI = 0.50 to 0.86, P = .003). Conclusions Compared with 1 year, shorter duration of adjuvant trastuzumab is associated with statistically significantly worse DFS and OS despite favorable cardiotoxicity profile. One year of targeted HER2 treatment should remain the standard adjuvant treatment in early-stage HER2-positive disease with appropriate cardiac monitoring.

GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain

“…This is especially advised for women >70 years of age and/or with comorbidities, that is, a high‐risk group for severe COVID‐19 disease if infected. Although Goldvaser's meta‐analysis [18] endorses 1 year of therapy, data from the PERSEPHONE study showed no worse patient outcomes with 6 months versus 12 months of adjuvant trastuzumab treatment in HER2‐positive early breast cancer [19]. Adjuvant anti‐HER2 therapy may be delayed for up to 2–3 months in patients receiving neoadjuvant chemotherapy in combination with anti‐HER2 antibodies. Adjuvant administration of trastuzumab‐DM1 (T‐DM1) is adequate for patients without pCR after neoadjuvant chemotherapy.…”

Adjuvant trastuzumab in early HER2-positive breast cancer: Journeying towards the optimal duration of therapy in South Africa

“…Several articles [8,[17][18][19][20][21][22] investigating shorter treatment durations for trastuzumab have been published subsequent to this initial review.…”

“…Six meta-analyses [17][18][19][20][21][22] were consi dered for this review; however, none met the inclusion requirements. They were either of low quality in terms of methodological rigour and/or failed to include the results from key clinical trials.…”

“…One study [21] was published prior to the finalisation of the PERSEPHONE study, while another [22] excluded the results from the PERSEPHONE, PHARE and HORG (Hellenic Oncology Research Group) [10] studies. Four studies [17][18][19][20] did not stratify for…”

The Clinical and Translational Research Activities at the INT – IRCCS “Fondazione Pascale” Center (Naples, Italy) during the COVID-19 Pandemic

“…In order to ensure breast cancer continued care and treatment and protect patients and healthcare professionals from the COVID-19 pandemic, a priority program has been developed to minimize patient hospitalization and ensure optimal patient care. In this perspective, instead of the proposed general deferral strategy [63], it was decided not to defer breast cancer treatment that have been classi ed as at medium/high priority by ESMO [64], while avoiding or delaying low priority interventions only. Patients and staff safety have been demanded to the general (strict) protection policy of the hospital.…”