PHARMACOTHERAPY

Immunotherapy for advanced endometrial carcinoma: Time for a paradigm shift?

SUMMARY

Over the past decade, immune checkpoint inhibitors (ICI) emerged as a new therapeutic pillar across a broad range of cancer types. An important characteristic of patients responding to ICI-based therapy consists of a high mutational burden in the tumours. In line with this, patients with microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) endometrial cancer (EC) proved to be particularly sensitive to ICI, leading to the approval of anti-PD-1 antibodies for patients with MSI-H/dMMR ≥2nd line recurrent setting. Responses to single-agent ICI have also been reported in a small proportion of patients with microsatellite stable (MSS) EC. However, a high unmet need remains for these patients. More recently, several phase III randomised controlled trials showed that adding an ICI to standard chemotherapy significantly delays the disease progression in patients with primary advanced or recurrent MSI-H/dMMR EC, but also, to a lesser extent, in MMR proficient (p)/MSS EC. This article will briefly review the available clinical trial data with ICI-based therapies in EC and will assess how this treatment modality could be integrated into the Belgian treatment paradigm for these patients.

(BELG J MED ONCOL 2024;18(2):49–59)

Head and neck cancer: The role of cisplatin

SUMMARY

Cisplatin has been the backbone of the treatment of patients with squamous cell carcinoma of the head and neck, both in recurrent/metastatic settings and in patients with locoregional disease. In patients with recurrent/metastatic disease and a combined positivity score (CPS) ≥20, cisplatin can be replaced by pembrolizumab. In patients with locoregional disease and treated with definitive chemoradiation or in the adjuvant setting, the 3-weekly high-dose cisplatin can be replaced by the weekly 40 mg/m² cisplatin regimen.

(Belg J Med Oncol 2023;17(2):52–7)

What are the treatment options for metastatic castration-resistant prostate cancer anno 2023?

SUMMARY

Patients developing metastatic castration-resistant prostate cancer are in most instances pre-treated with androgen deprivation treatment and a newer androgen receptor-targeting agent in the metastatic castration-sensitive setting.

In this article, I discuss the first- and second-line treatment options in this patient population.

(BELG J MED ONCOL 2023;17(1):15–8)

The benefit of anticancer drugs

SUMMARY

New anticancer drugs are continuously developed and show statistically significant differences compared to the standard treatment. However, their clinical impact is not always shown. In this review, two systems to evaluate the meaningful clinical benefit are discussed: the ESMO-MCBS, developed by ESMO, and the ASCO value framework, proposed by ASCO. Both systems evaluate clinical meaningful effects of new anticancer drugs based on available clinical research, and grade them according to the system they developed. Whereas the ESMO-MCBS is a tool directed to guide development and health care system professionals, the ASCO value framework is a tool to help the medical oncologist and the patient to make an informed decision in relation to the value of a new treatment, including costs.

(BELG J MED ONCOL 2022;16(7):355–9)

Vascular malformations: Repurposing the role of anti-cancer targeted molecular inhibitors

SUMMARY

Vascular malformations are rare diseases that result from anomalies in the angiogenesis process. They are subdivided into capillary, lymphatic, venous, arteriovenous, and mixed malformations, according to the type of affected vessels. Until a few years ago, therapeutic options were limited to sclerotherapy and/or surgery, but these treatments are rarely curative or not feasible. Most vascular malformations are caused by inherited or somatic mutations in various genes. These mutations are similar to oncogenic mutations detected in cancer, leading to hyperactivity of important signalling pathways, including MAPK and PI3K/AKT/mTOR cascades. This article highlights the role of targeted molecular inhibitors as therapies for vascular anomalies via repurposing of anticancer drugs.

(BELG J MED ONCOL 2022;16(6):293–99)

Current treatment patterns of advanced hormone receptor-positive, HER2-negative breast cancer in Belgium

SUMMARY

Several treatment guidelines exist for hormone receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC), but various factors influence their local implementation. We performed a 3-round Delphi methodbased study in search of a consensus regarding HR+/HER2- aBC management in Belgian practice. Panel questionnaires included questions related to treatment patterns, drug-drug interactions (DDIs) and side-effect management (SEM). A consensus threshold of 75% was applied. The results were evaluated for concordance with the ABC5 guidelines. Treatment patterns in HR+/HER2- aBC reached moderate to high consensus among Belgian oncologists and showed high concordance with ABC5 guidelines. A CDK4/6 inhibitor is the preferred first-line treatment, combined with an aromatase inhibitor or with fulvestrant in the endocrine-sensitive and -resistant setting, respectively. Alpelisib-fulvestrant is the preferred second-line treatment in presence of a PIK3CA-activating mutation. Some practices regarding DDI and SEM needed further discussion before reaching consensus highlighting the need for additional training and incorporation of these topics in guidelines.

(BELG J MED ONCOL 2022;16(4):176–86)

Neoadjuvant therapy for resectable and borderline resectable pancreatic cancer: Is radiotherapy worthwhile?

SUMMARY

For resectable pancreatic cancer, (RPC) or borderline resectable pancreatic cancer (BRPC) the standard treatment is surgery followed by adjuvant chemotherapy. There is a worldwide ongoing discussion on the benefit of neoadjuvant treatment instead of adjuvant treatment for these patients. Interpretation and comparison of studies is hard because of a difference in patient selection between studies about these two strategies. Reporting by intention to treat and randomised clinical trials are essential.

In the first decade of the 21^st century, many studies and reviews suggested superiority of the neoadjuvant approach in RPC and BRPC for patients with resected pancreatic cancer. Several reviews also suggested an advantage by intention to treat. The first two randomised trials failed due to lack of accrual, and the third discontinued because of changed standard regimens. Since 2018, two randomised trials were published and one presented. A meta-analysis of these six RCTs, four of which with neoadjuvant chemoradiotherapy, and all with gemcitabine based regimens, revealed that with neoadjuvant treatment overall survival improved compared to upfront surgery for both RPC and BRPC. Since local control and pathological factors such as pN classification and R0 resection rate are invariably better after neoadjuvant treatment, radiotherapy probably plays an important role.

Currently, more effective treatments are available, in particular FOLFIRINOX and gemcitabine + nab-paclitaxel are considered the best available chemotherapeutic schedules and stereotactic body radiotherapy (SBRT) is superior to conventional radiotherapy. Future studies should investigate the role of FOLFIRINOX or gemcitabine plus nab-paclitaxel combined with SBRT.

BELG J MED ONCOL 2021;15(3):117-22