H. Wildiers MD, PhD

Belgian clinical practice guidelines for the treatment of patients with HER2-positive advanced breast cancer

SUMMARY

HER2-targeted agents are the central component of HER2-positive metastatic breast cancer (MBC) treatment. The combination of trastuzumab, pertuzumab and a taxane is the preferred first-line regimen in most settings. For patients with disease relapse after adjuvant therapy, treatment decisions in the first-line are influenced by the treatment-free interval and the regimens used in the (neo)adjuvant setting. T-DXd has been recently established as the preferred second-line therapy. T-DM1, or the combination of tucatinib, trastuzumab and capecitabine, are reasonable third-line options, although efficacy and safety data of these regimens after prior exposure to T-DXd are lacking. In fourth and later lines, trastuzumab duocarmazine, neratinib plus capecitabine, margetuximab plus chemotherapy, lapatinib-based combinations or the continuation of trastuzumab with different chemotherapy partners are valid alternatives.

(BELG J MED ONCOL 2022;16(6): 287–92)

Congress highlights SABCS 2021

SUMMARY

The hybrid SABCS 2021 could only attract a few hundred life attendees, but like every year, several key abstracts were presented. In early stage, a meta-analysis on aromatase inhibitor versus tamoxifen in premenopausal ER+ patients showed lower recurrence with aromatase inhibitors, while the impact on overall survival remains unclear. An EBCTCG meta-analysis showed no benefit for an anthracycline-taxane adjuvant chemotherapy regimen compared to a taxane only regimen, if the taxane was given sequentially after the anthracycline, confirming the role of anthracycline-free chemotherapy regimens in a large proportion of patients with early breast cancer. In ER+ metastatic disease, the new SERD elacestrant was more potent than classical endocrine therapy after progression on first/second line endocrine therapy. Datopotamab deruxtecan is a promising new ADC targeting TROP2 with clear activity in triple negative disease. In HER2 positive disease, T-DXd displayed substantial antitumour effect on brain metastases, and pyrotinib can be added to the list of highly potent HER2 tyrosine kinase inhibitors. In patients with HER2 mutations, neratinib showed clear antitumour activity both in ER positive and triple negative metastatic breast cancer. In the surgery field, black and Hispanic women were shown to be at higher risk for breast cancer related lymphedema after axillary lymph node dissection. The Italian SINODAR-ONE trial built further on the Z0011 trial and confirmed that axillary surgery can be omitted in patients with breast cancer patients and one or two macro metastatic sentinel nodes.

(BELG J MED ONCOL 2022;16(2):79–87)

Genomics of metastatic breast cancer

SUMMARY

The purpose of this review is to highlight the recent knowledge gathered on the genomics of metastatic breast cancer (BC), together with the clinical implications. Through large sequencing efforts, the genomic profile of BC is increasingly being deciphered, with a limited number of those findings having resulted in genomicmatched treatment options. The pace at which new discoveries are made is highest in the early setting, where large samples can easily be accessed through leftover tissue of resection specimens, and smaller diagnostic biopsies are also available. In the metastatic setting however, residual tissue from clinically indicated biopsies or resections are scarce. Some efforts have been undertaken through (inter)national, institutional, clinical trial- or patient-driven initiatives. They have highlighted important differences between the genomic landscape of metastatic versus primary tumour tissues. Especially in hormone receptor positive HER2 negative (HR+/HER2-) disease, driver mutations continue to accumulate after dissemination, most of them in the ESR1 or ERBB2 genes, or in genes involved in transcription regulation, MAPK- or PI3K-signaling pathways. Importantly, the genomic landscape is not homogeneous even within one patient, and significant heterogeneity is seen on an intra-patient, inter-lesion and intra-lesion level. This poses clinical challenges, with different subclones possibly harbouring differential sensitivity to systemic treatments and single biopsies not accurately reflecting the full molecular profile. Finally, through liquid biopsies, a more complete and less invasive insight into the tumour’s characteristic could theoretically be retrieved. However, it is unclear how well these profiles correlate with the actual diversity of the different lesions. Importantly, rapid autopsy programs have been shown to enhance research on the genomics of metastatic BC, and one such program was recently launched at UZ/KU Leuven.

(BELG J MED ONCOL 2022;16(1):18–28)

Highlights in breast cancer

At this year’s annual meeting of the European Society of Medical Oncology (ESMO) experts shared some game-changing data for the treatment of breast cancer (BC). In advanced HER2+ metastatic breast cancer m(BC), the DESTINY-Breast03 trial performed a head-to-head comparison of T-DM1 and trastuzumab deruxtecan (T-Dxd) following initial treatment with trastuzumab and a taxane, showing a major PFS benefit for T-DXd without major toxicity issues, establishing T-DXd as the new standard of care in this setting. In luminal breast cancer, the final analysis of the GIM-4 study supports the use of 7 years instead of 5 years adjuvant endocrine therapy in postmenopausal patients with hormone receptor positive (HR+)/HER2- early BC. For advanced stage HR+/HER2- BC, the MONALEESA-2 study shows >1y OS benefit when adding the CDK4/6 inhibitor ribociclib to letrozole as first-line treatment. Finally, in triple negative breast cancer (TNBC), the phase III BrighTNess study showed that addition of carboplatin to neoadjuvant chemotherapy provides long term EFS benefit. In metastatic TNBC, OS data of KEYNOTE-355 further support the use of first-line pembrolizumab plus chemotherapy in advanced PD-L1+ TNBC.

(BELG J MED ONCOL 2021;15(8):390–7)

The value of population-based databases to evaluate long-term patient outcomes: A multicentric research project in older patients with cancer

SUMMARY

The use of population-based data is a relatively accessible and cost-effective approach to study long-term outcomes in oncology. Also in older patients with cancer, longer-term outcome studies are limited and population-based data could help address this gap. Under the lead of UZ Leuven and the Belgian Cancer Registry (BCR), a national study was initiated to explore the association between the general health status of older patients with cancer as assessed by geriatric screening and assessment, and long-term outcomes as captured by population-based data. To this extent, data previously gathered within the context of a multicentre clinical study will be linked with three population-based databases: cancer registration data from BCR, healthcare reimbursement data from InterMutualistic Agency and hospital discharge data from Technical Cell. The major advantage of these population-based data is their longitudinal nature, which allows to follow a (sub)population across several years. The downside is their lack of clinical information. One way to partially overcome this limitation is to supplement population-based data with primary study data to investigate more clinically relevant outcomes. Although often scientifically interesting and appealing, coupling with population-based data demands intensive administrative efforts including an authorisation demand at the Information Security Committee. During the whole process, special attention should be given to privacyrelated aspects of the use and linkage of these data to ensure confidentiality.

BELG J MED ONCOL 2021;15(7):362-6)

Geriatric syndromes in oncology: what does the oncologist need to know?

SUMMARY

A ‘Geriatric Syndrome’ is characterised by its multifactorial origin. A combination of impairments leads to one specific condition that is typical for frail older patients. The rising incidence of cancer among older adults makes it interesting for the oncologist to understand common geriatric syndromes. The following geriatric syndromes are presented in this article:

Delirium: In patients with cancer, the prevalence of delirium is high. In end-stage malignant disease a prevalence near 90% has been reported. The pathophysiology is characterised by an equilibrium between predisposing and precipitating factors. The more predisposing factors, the less precipitating factors are required to develop delirium, and vice versa. Delirium is often underdiagnosed, although it leads to increased morbidity and mortality. Screening tools, such as the Confusion Assessment Method or the 4 ’A’s Test, could help the oncologist to discover delirium. Prevention and non-pharmacological therapy are the cornerstone of the approach. Pharmacological therapy is only appropriate when non-pharmacological therapy is not successful or if delirium could harm the patient.

Cognitive decline: In Belgium, the prevalence of dementia is estimated at 7.4% in adults aged 65 and over. Apart from dementia, cognitive decline in oncologic patients could also be provoked by cancer or its treatment. Cognitive decline is prognostic for overall survival in older patients with cancer. The Mini-Cog is an easy screening tool for cognitive decline, but more extensive testing, e.g. by means of a Mini Mental State Examination, can also be applied. Referral to a memory clinic should be considered, taking into account oncological diagnosis and prognosis.

Urinary incontinence: About 15 to 35% of patients older than 60 years have urinary incontinence. Urinary incontinence is associated with falls and fractures, pressure ulcers, and urinary infection. It has an emotional impact, affects quality of life and is associated with higher depression rates. In predisposed patients, precipitating factors could trigger incontinence. Prevention is of high importance and is primarily aimed at treating the precipitating factors. Pharmacological treatment blocking muscarinic receptors is associated with important side effects.

Functional decline: One third of patients receiving chemotherapy suffer from functional decline. Functional decline is prognostic for overall survival. Baseline functional assessment before initiation of treatment is important. The oncologist has to define predisposing and precipitating factors and to estimate the risk of functional decline. A multidisciplinary approach with physiotherapists, occupational therapists, nurses and social workers is warranted to achieve optimal rehabilitation.

Falls: Thirty percent of patients older than 65 years have fall incidents. Ten percent of falls lead to residual injuries. Cancer and its treatment increase the risk of falling. Bone metastases or cancer therapy can lead to more severe injuries. Falls are often preventable. Therefore, risk stratification and formulation of a multifactorial fall prevention plan by a multidisciplinary team is warranted.

(BELG J MED ONCOL 2021;15(6):270-7)

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)