H. Wildiers MD, PhD

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)

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)