Is the duration of adjuvant trastuzumab debate still clinically relevant?

Hurvitz, Sara A.

doi:10.1016/s0140-6736(19)30946-8

Cited by 5 publications

(5 citation statements)

References 17 publications

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“…All studies, except for the PERSEPHONE study, failed to demonstrate noninferiority of shorter versus longer duration of adjuvant trastuzumab. Meanwhile, the absolute difference in survival was 2% on average [ 46 ]. These data may be reassuring because in certain groups of patients, particularly those with low risk of relapse and logistic limitations, the survival outcome will not be greatly compromised if the adjuvant trastuzumab duration is limited to 6 months.…”

Section: Discussionmentioning

confidence: 99%

Suggested Modifications to the Management of Patients With Breast Cancer During the COVID-19 Pandemic: Web-Based Survey Study

Elsamany¹,

Elbaiomy²,

Zeeneldin³

et al. 2021

JMIR Cancer

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Background Management of patients with cancer in the current era of the COVID-19 pandemic poses a significant challenge to health care systems. Breast cancer is the most common cancer internationally. Breast cancer is a disease that involves surgery, chemotherapy, hormonal therapy, targeted therapy, radiotherapy, and, more recently, immunotherapy in its management plan. The immune system requires months to recover from these medications, and this condition is even worse in patients with metastatic breast cancer who need ongoing treatment with these drugs. Some of these drugs, such as inhibitors of cyclin-dependent kinases 4 and 6, can cause rare but life-threating lung inflammation. Patients with breast cancer who have metastatic disease to the lungs can experience deterioration of disease symptoms with COVID-19 infection. Oncologists treating patients with breast cancer are facing a difficult situation regarding treatment choice. The impact that COVID-19 has had on breast cancer care is unknown, including how to provide the best care possible without compromising patient and community safety. Objective The aim of this study was to explore the views of oncologists regarding the management of patients with breast cancer during the COVID-19 pandemic. Methods A web-based SurveyMonkey questionnaire was submitted to licensed oncologists involved in breast cancer management in Saudi Arabia, Egypt, and United Arab Emirates. The survey focused on characteristics of the participants, infection risk among patients with cancer, and possible treatment modifications related to different types of breast cancer. Results The survey was completed by 82 participants. For early hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, 61 of the 82 participants (74%) supported using neoadjuvant hormonal therapy in selected patients, and 58% (48/82) preferred giving 6 over 8 cycles of adjuvant chemotherapy when indicated. Only 43% (35/82) preferred inhibitors of cyclin-dependent kinases 4 and 6 with hormonal therapy as the first-line treatment in all patients with metastatic HR-positive disease. A total of 55 of the 82 participants (67%) supported using adjuvant trastuzumab for 6 instead of 12 months in selected patients with HER2-positive breast cancer. For metastatic HER2-positive, HR-positive breast cancer, 80% of participants (66/82) supported the use of hormonal therapy with dual anti-HER2 blockade in selected patients. The preferred choice of first-line treatment in metastatic triple negative patients with BRCA mutation and programmed cell death 1 ligand 1 (PD-L1) <1% was poly(adenosine diphosphate–ribose) polymerase inhibitor according to 41% (34/82) of the participants, and atezolizumab with nab-paclitaxel was preferred for PD-L1 >1% according to 71% (58/82) of the participants. Conclusions Several modifications in breast cancer management were supported by the survey participants. These modifications need to be discussed on a local basis, taking into account the local infrastructure and available resources.

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Section: Discussionmentioning

confidence: 99%

Suggested Modifications to the Management of Patients With Breast Cancer During the COVID-19 Pandemic: Web-Based Survey Study

Elsamany¹,

Elbaiomy²,

Zeeneldin³

et al. 2021

JMIR Cancer

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“…Whether a shorter duration of trastuzumab is adopted more broadly, or further trials at de-escalation with shorter duration are attempted, will likely be with an emphasis on pharmacoeconomic outcomes as discussed by the authors of the PHARE trial and PERSEPONE commentary [ 12 , 46 ]. The drug costs associated with trastuzumab therapy will improve with the introduction of biosimilars, but a shorter duration may still improve patient’s quality of life and decrease the indirect costs associated with treatment such as cardiac monitoring, management of toxicity, and help free up resources for the ever increasing and large current demand for cancer care services.…”

Section: Discussionmentioning

confidence: 99%

Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis

et al. 2020

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One year of adjuvant trastuzumab is considered the standard treatment for patients with HER2 positive breast cancer. However, a shorter duration of trastuzumab may be associated with reduced costs and side effects. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant trastuzumab are not consistent and have not been systematically reviewed using a non-inferiority meta-analysis approach. We conducted a systematic review and meta-analysis of randomized trials to assess whether a shorter duration of adjuvant trastuzumab was non-inferior to one year of treatment or not. The non-inferiority margin for the meta-analysis was pre-defined as the median of the margins of all the trials included. Data of 11,376 patients from 5 trials were analyzed. Non-inferiority margins in included studies varied from 1.15 to 1.53 with median of 1.29 for HR of DFS. A shorter duration of trastuzumab was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03–1.24) but inconclusive for OS (HR 1.14, 95%CI 1.00–1.30). In a subgroup analysis for DFS outcome, shorter therapy was non-inferior in patients with ER positive disease (HR 1.10, 95%CI 0.95–1.28) and those with sequential therapy (HR 0.97, 95%CI 0.75–1.27) and when the duration of treatment was 6 months (HR 1.09, 95%CI 0.98–1.22). Although a shorter duration of adjuvant trastuzumab was non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer based on our HR margin of 1.29, any benefit of a shorter duration comes at a loss of efficacy with an increase in absolute risk up to 3.9% for 5 year DFS. Whether the potential increased risk is clinically acceptable for the benefits of a shorter duration remains debatable.

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“…We also need a longer follow-up in the ER-positive subgroup to assess the benefit of adjuvant trastuzumab as relapses in this subgroup can occur late. 18 Surprisingly heavy nodal positivity did not influence the outcome. One reason for this could be that the authors defined pathologically staged N3 axillary lymph node as ≥4 nodes instead of the American Joint Committee on Cancer (AJCC) staging that defines N3 as ≥10 nodes.…”

mentioning

confidence: 89%

“…17 We need more trials of adjuvant trastuzumab with nonanthracycline-based regimens to see the effectiveness of a shorter duration of trastuzumab. 18…”

mentioning

confidence: 99%

“…17 We need more trials of adjuvant trastuzumab with nonanthracycline-based regimens to see the effectiveness of a shorter duration of trastuzumab. 18 Individually five out of six trials failed to prove noninferiority of shorter duration of trastuzumab against 1-year trastuzumab. However, overall, the meta-analysis was able to show noninferiority for DFS and OS albeit with a 25% possibility of inferiority at upper CI.…”

mentioning

confidence: 99%

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