K. Punie MD

Highlights in breast cancer

ASCO 2021 featured one crucial, practice-changing trial in early breast cancer: the OlympiA trial showed that one year of adjuvant olaparib improves invasive disease-free survival by 8.8% compared to placebo, when administered to high risk early breast patients (triple negative or hormone sensitive and HER2 negative) with a germline BRCA1 or 2 mutation. Furthermore, ECOG-ACRIN EA1131 failed to show improved outcome in triple negative breast cancer treated without pathological complete response after neoadjuvant chemo-therapy with platinum based chemotherapy compared to the current standard capecitabine. GeparNUEVO for the first time showed long term outcome with anti-PD(L)1 therapy administered with neoadjuvant chemotherapy in triple negative breast cancer. In the advanced setting, interesting overall survival updates of the PALOMA-3 and MONALEESA-3 studies were presented. Furthermore, the SYsucc-002 trial demonstrated that trastuzumab plus endocrine therapy was non-inferior to and had fewer toxicities compared with trastuzumab plus chemotherapy in patients with HR+/HER2- metastatic breast cancer. In addition, this article will touch upon several other studies that are notable.

(BELG J MED ONCOL 2021;15(5):208-17)

A case of HER2-positive breast cancer with rapidly progressing CNS metastases

SUMMARY

A 53-year old woman previously treated for stage IIIc Her2-positive breast cancer presented to the outpatient oncology department with symptoms of holocranial headache irradiating to the neck in combination with morning sickness and vomitus. Brain CT showed multiple cerebellar metastases with signs of tonsillar herniation through the foramen magnum. Since radiotherapy was deemed unsafe given the possibility that transient increase of intracranial pressure could worsen the herniation, urgent treatment with corticosteroids and capecitabine-lapatinib was started. The metastases and peritumoral oedema initially responded well, which allowed subsequent pancranial radiotherapy after three weeks of systemic therapy. We provide a short overview of studies showing that systemic therapy can induce tumour response in brain metastases related to HER2+ positive disease.

BELG J MED ONCOL 2021;15(3):123-7

Systemic treatment landscape and algorithm for hormone-receptor positive, HER2 negative advanced breast cancer

SUMMARY

Hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer accounts for 65% of all metastatic breast cancer (MBC) cases. With the advent of CDK4/6 inhibitors, single-agent endocrine therapy (ET) is no longer the only first-line systemic treatment option for the vast majority of patients presenting without visceral crisis. Other endocrine-based treatment options are emerging in further lines, with the goal to delay the administration of chemotherapy as long as possible. The optimal sequence of treatment is unknown. We here present a review of the available treatments and propose a treatment algorithm taking into account the latest therapeutic developments.

(BELG J MED ONCOL 2021;15(1):20-33)

Immunotherapy for the treatment of triple-negative breast cancer

While immune checkpoint inhibitors (ICIs) demonstrated a convincing efficacy with durable responses in many cancer types, the single agent efficacy of ICIs in patients with advanced triple-negative breast cancer (TNBC) proved to be low. In a successful attempt to boost this clinical activity, ICIs were subsequently combined with chemotherapy in patients with metastatic TNBC. Following the positive results in the metastatic setting, ICIs are now also under evaluation in combination with neoadjuvant chemotherapy in patients with early TNBC. This review provides an overview of the results obtained with ICI in TNBC, from the disappointing results with ICI monotherapy, over the emerging data with ICI-chemotherapy combinations in the neoadjuvant setting to the pivotal, practice-changing results obtained with atezolizumab and atezolizumab in combination with chemotherapy in metastatic TNBC patients.

Highlights in breast cancer

During the 2020 Virtual ESMO meeting, long-awaited results were presented of several important breast cancer studies. For hormone receptor positive (HR+) breast cancer, ESMO 2020 featured conflicting results on the use of CDK4/6 inhibitors in the adjuvant treatment of patients with hormone-receptor positive (HR+) early breast cancer. In HR+ metastatic breast cancer, final overall survival data were presented of the SOLAR-1 trial evaluating alpelisib in PIK3CA mutant patients. In triple negative breast cancer (TNBC), new data on immune therapy were presented. In early-stage TNBC, the addition of atezolizumab to neoadjuvant chemotherapy resulted in a significant increase in the rate of pathological complete responses (pCR). In the metastatic setting, final results of the IMpassion130 trial confirmed the benefit of atezolizumab combined with nab-paclitaxel as first-line treatment for metastatic PD-L1 positive TNBC. Unexpectedly, the IMpassion131 trial evaluating atezolizumab plus paclitaxel in first-line treatment of patients with metastatic TNBC failed to meet its primary endpoint. Finally, the phase III randomized controlled ASCENT trial identified the antibody-drug conjugate (ADC) sacituzumab govitecan as a safe and highly effective treatment option for heavily pre-treated metastatic TNBC patients.

Clinical management of first-line advanced triple-negative breast cancer patients

SUMMARY

Chemotherapy has represented the main treatment option for patients with advanced triple-negative breast cancer for a long time. However, due to our better understanding of tumour biology, recent clinical trials led to a change in the treatment paradigm of this disease, identifying clinically relevant subgroups with different therapeutic options. Both clinical and biological factors have become relevant and need to be considered in the treatment decision algorithm of this heterogeneous disease.

(BELG J MED ONCOL 2020;14(7):333-38)

Highlights in breast cancer

ABSTRACT

The 2019 edition of the annual ESMO meeting proved to be a grand cru when it comes to breast cancer studies. In early triple negative breast cancer (TNBC), the KEYNOTE-522 trial demonstrated a significant improvement of pathological complete response rate with the addition of pembrolizumab to neoadjuvant chemotherapy, irrespective of PD-L1 status. In addition to this, the prognostic value of tumour-infiltrating lymphocytes was confirmed in a pooled analysis of patients with TNBC who did not received adjuvant chemotherapy. In the field of metastatic breast cancer, much attention went to overall survival data that were presented for the CDK4/6-inhibitors ribociclib and abemaciclib in combination with fulvestrant (MONALEESA-3, MONARCH 2). Interesting results of the phase III BROCADE3 trial were presented in which the addition of the PARP inhibitor veliparib to carboplatin and paclitaxel was evaluated in patients with advanced HER2-negative breast cancer and a germline BRCA mutation. Regarding checkpoint inhibitors in metastatic TNBC, a read-out of a phase III trial with pembrolizumab compared to standard chemotherapy in second- and third-line was presented, as well as important translational data on different immunohistochemical PD-L1 assays from IMpassion130. Finally, two oral presentations focused on the use of CDK4/6-inhibitors in different combination regimens in metastatic HER2-positive breast cancer (MonarcHER) and in TNBC.