In 2015, academic-led trials provided evidence for safe de-escalation of adjuvant treatment in early stage breast cancer and answered important questions related to adjuvant regional irradiation and optimal first-line chemotherapy in advanced-stage disease. The impact of such studies that will affect clinical practice is summarized in an excellent article by Martine Piccart and Isabelle Gingras, published in the Nature Reviews Clinical Oncology.
Drs Piccart and Gingras wrote: “Academic research in oncology, which is patient-centred and provides answers to questions with limited or no commercial interest, has been under threat in the past decade. However, seven academic clinical trials reported in 2015 reassure that research remains alive, and that academic clinical investigators continue to find the energy needed to secure the financial support for this critically important research.”
They wrote that the excellent disease-free survival observed with adjuvant paclitaxel and trastuzumab without anthracyclines have set a new standard of care for the adjuvant treatment of small (T1–T2), node-negative, HER2-positive breast cancer, and highlighted the possibility to de-escalate treatment for low-risk, early stage, HER2-positive disease. The decision to withdraw anthracyclines is supported by the extremely low rate of distant disease recurrence observed at a median follow-up of nearly 4 years following 3 months of weekly paclitaxel and 1 year of trastuzumab.
The very low incidence of breast-cancer recurrence observed in node-negative patients with a 'low risk' Oncotype DX® score confirms that these patients should be spared adjuvant chemotherapy. TAILORx is a very large prospective, academic study, designed to refine adjuvant chemotherapy withdrawal. The trial reported the excellent outcome in women with a 'low-risk' Oncotype DX® score and showed that following adjuvant endocrine therapy, 98.7% of these women remain free from recurrence at any site, highlighting that chemotherapy can be avoided in these patients.
Adjuvant trials that aim to optimise radiotherapy fields, doses, or schedules are challenging in term of difficulties in funding and they require large numbers of patients and very long follow-up. Two such trials with mature 10-year follow up were published, and provided consistent results despite differences in study size and patient selection: the addition of regional nodal irradiation to whole-breast or thoracic-wall radiotherapy does not improve overall survival, but does reduce the rate of local and distant breast cancer recurrence.
In the study of upfront carboplatin versus docetaxel in women with metastatic triple-negative breast cancer, a superior response rate for the alkylating agent over the taxane was demonstrated in 43 patients with BRCA-mutated tumours, representing around 8% of the trial population. When receiving carboplatin, patients with BRCA-mutated tumours had a median progression-free survival of 6.8 months compared with 3.1 months in BRCA-wild-type patients.
In 2015, two studies demonstrated that CDK4/6 inhibitor, palbocilib can improve progression-free survival of patients with metastatic disease in both the first-line and second-line settings, and palbociclib in combination with letrozole received conditional FDA approval for the first-line treatment of oestrogen-receptor-positive, HER2-negative metastatic breast cancer.
About other academic advances in breast cancer reported in the article, you can read in a full paper available through myESMO Journal access programme.
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