H. Wildiers MD, PhD

Highlights in HER2-positive breast Cancer

In this article, some highlights on human epidermal growth factor 2 (HER2)-positive breast cancer presented during SABCS 2024 are discussed. In the early setting, several studies investigated neoadjuvant chemotherapy de-escalation strategies. Furthermore, the role of margetuximab in early breast cancer (EBC) was investigated in the phase II MARGOT trial. In the metastatic setting, the addition of palbociclib to endocrine and anti-HER2 therapy was evaluated in the PATINA trial including patients with hormone receptor (HR)-positive HER2-positive metastatic breast cancer (MBC). Finally, the final results of the PHILA trial were presented.

Highlights in HR-positive breast cancer

With respect to hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, a post hoc analysis of the TAILORx trial was presented during SABCS 2024, in which the potential benefit of adding adjuvant anthracyclines to a taxane-containing regimen was evaluated according to genomic risk using Oncotype DX. In addition, in early breast cancer (EBC), nab-paclitaxel was compared to solvent-based (sb)-paclitaxel in the chemotherapy cohort of the WSG-ADAPT HR+/HER2- trial. Also, additional analyses related to the NATALEE trial were presented, including the effect of adjuvant ribociclib dose reduction on efficacy, and assessment of the benefit of ribociclib plus non-steroidal aromatase inhibitors (NSAIs) on distant disease-free survival (dDFS) across several subgroups. In the metastatic setting, SABCS 2024 featured the results of the phase III EMBER trial, which evaluated the efficacy and safety of imlunestrant as monotherapy or combined with abemaciclib in patients with endocrine-resistant oestrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC); they either progressed during adjuvant or first-line endocrine therapy (ET) and prior cyclin dependent kinase 4 or 6 inhibitor (CDK4/6i) was allowed. Moreover, the PADMA trial evaluated the use of palbociclib plus ET vs mono-chemotherapy in women with high-risk, previously untreated, HR-positive, HER2-negative MBC. Finally, an exploratory post hoc analysis of the DESTINY-Breast06 trial assessed the efficacy of trastuzumab deruxtecan (T-DXd) according to pace of progression on prior endocrine-based therapy.

Highlights in breast cancer

SUMMARY

At ESMO 2024, updated results of the KEYNOTE-522 study showed for the first time overall survival (OS) benefit when adding pembrolizumab to neoadjuvant chemotherapy in patients with early-stage triplenegative breast cancer (TNBC). In addition, real-world evidence indicated that oestrogen receptor (ER)-low human epidermal growth factor receptor 2 (HER2)-negative disease treated with the neoadjuvant KEYNOTE-522 regimen achieved very high pathological complete response (pCR) rates and should preferably be treated as TNBC. Updated results from the NATALEE trial further reinforced the efficacy of combining a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor with endocrine therapy in patients with early-stage hormone receptor (HR)-positive breast cancer at risk of recurrence. Furthermore, preliminary evidence showed promising activity in patients with luminal B-like breast cancer treated with preoperative radiotherapy (RT) plus immuno-chemotherapy. Additionally, the HypoG-01 trial supports the use of hypofractionated RT (40 Gy/15 fractions in three weeks) to irradiate loco-regional nodes in patients with early-stage breast cancer. In the metastatic setting, the addition of capivasertib to first-line paclitaxel did not significantly improve survival in patients with TNBC. In addition, first-line treatment with CDK4/6 inhibitors and endocrine therapy confirmed efficacy for patients with HR-positive HER2-negative breast cancer with aggressive disease criteria compared to upfront chemotherapy. Moreover, in patients with HR-positive breast cancer, a large proportion of patients currently categorised as having tumours with an immunohistochemical (IHC) score of 0 at local testing, are HER2-low (IHC 1 or 2+) or ultralow (IHC >0 and <1) at retesting and can also benefit from trastuzumab deruxtecan (T-DXd). Finally, substantial and durable intracranial clinical activity was seen in patients with HER2-positive breast cancer with stable and active brain metastases treated with T-DXd.

(BELG J MED ONCOL 2024;18(8):294–302)

Long-term outcomes in older patients with cancer and the association with geriatric screening and assessment results

SUMMARY

Oncology care is tumour-centric by tradition, but especially in older patients, a more holistic approach is needed that takes into account each aspect of the patient’s health status and not just the tumour. Identifying areas of vulnerability with geriatric screening (GS) and/or geriatric assessment (GA) is crucial in providing patient-oriented and multidisciplinary care that is tailored to the patient’s general health status. The results of GS/GA allow the treating physician to apply clinical judgment based on an estimate of biological age to optimise cancer treatment decisions. The use of GS/GA is, however, not yet widespread in Belgian oncology practice so further evidence on what GS/GA results can contribute, particularly regarding long-term outcomes, was needed to further stimulate the systematic implementation. This study specifically aimed to explore the association between the GS (with Geriatric 8 or G8) / GA and long-term outcomes using linked clinical and population-based data from a cohort of older patients with cancer. It was demonstrated that older patients with an abnormal G8 score at cancer diagnosis had a significantly lower 10-year overall survival compared to patients with a normal G8 score. Furthermore, patients with an abnormal baseline G8 score displayed higher healthcare utilisation across primary care, hospital care, and residential care in the three years after cancer diagnosis. In deceased patients with an abnormal baseline G8 score, functional and cognitive impairment identified with GA at cancer diagnosis was associated with less specialised palliative care use in the last three months of life.

(BELG J MED ONCOL 2024;18(4):160–3)

Highlights in breast cancer

SUMMARY

At ESMO 2023, updated results of monarchE and NATALEE further reinforced the efficacy and safety of combining a CDK4/6 inhibitor with endocrine therapy (ET) in patients with early-stage hormone receptor positive (HR+) breast cancer (BC). In addition to this, the CheckMate 7FL and KEYNOTE-756 studies demonstrated a potential clinical benefit of adding an immune checkpoint inhibitor to neoadjuvant chemotherapy and adjuvant ET in this setting. In early-stage triple negative breast cancer (TNBC), updated results of the KEYNOTE-522 study confirmed the benefit of perioperative pembrolizumab, while the NeoTRiP trial, assessing the addition of atezolizumab to neoadjuvant chemotherapy, did not show a significant benefit in event-free survival (EFS). In metastatic disease, promising results were obtained with new selective oestrogen receptor degraders (SERD) and antibody-drug conjugates (ADC). In addition, results of a real-world study indicate that patients with HER2-/ER-low disease should preferably be treated as TNBC.

(Belg J Med Oncol 2023;17(8):304–12)

Highlights in breast cancer

The 2023 ASCO meeting again featured several ground-breaking presentations in the field of breast cancer (BC). Early-stage highlights include the long-awaited data of the NATALEE trial assessing adjuvant ribociclib in combination with endocrine therapy (ET) and the PHERGain trial exploring chemotherapy de-escalation using 18F-FDF PET/CT metabolic response assessment. Other studies discussed new molecular biomarkers for recurrence and response, and the impact of ET timing intake on outcomes. Finally, flibanserin was shown to be effective in countering sexual dysfunction in BC patients receiving adjuvant ET. In the metastatic setting, the SONIA trial questioned the universal use of CDK4/6 inhibitors in the first line treatment of patients with hormone-receptor (HR) positive metastatic BC. Furthermore, a pooled analysis of the DESTINY-Breast01, -02, and -03 trials reaffirmed trastuzumab deruxtecan as an effective treatment option for patients across all age subgroups in HER2-positive BC. Finally, a less toxic capecitabine regimen emerged as an alternative to standard treatment in metastatic BC. These results, along with other important findings, are summarised in this report. We would like to acknowledge Prof. Hans Wildiers and Prof. Patrick Neven (University Hospitals Leuven) for their help in selecting the abstracts and adding a clinical interpretation to this overview.

(BELG J MED ONCOL 2021;15(5):193–201)

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)