REVIEW ONCOLOGY

ALK-inhibitors in NSCLC: a tabulated review of randomised phase III trials

Three inhibitors ALK-inhibitors have been assessed in six randomised phase III trials in patients with advanced anaplastic lymphoma kinase (ALK) positive Non Small-Cell Lung Cancer (NSCLC). Patient and tumour characteristics, efficacy, and safety results are summarised in Tables 1, 2, and 3, respectively. Progression-free survival was the primary endpoint in all trials. In first-line, alectinib was superior to crizotonib, and both crizotinib and ceritinib were superior to pemetrexed plus platinum. Crizotinib and ceritinib were superior to pemetrexed or docetaxel in previously treated patients.
(BELG J MED ONCOL 2018;12(6):275–278)

Emerging concepts in urothelial cancer

Treatment for urothelial cancer has undergone rapid change. Cisplatin based chemotherapy should be given in the neo-adjuvant setting in muscle invasive bladder cancer and could play a role in trimodality therapy when combined with surgery and radiotherapy. Genetic profiling has differentiated several subtypes of urothelial cancer, mimicking progress seen in breast cancer. Of these subtypes, p53 like tumours are less likely to respond to neo-adjuvant chemotherapy. In metastatic urothelial cancer, systemic immunotherapy (checkpoint inhibitors) has shown promising results in first line and second line patients. In a phase III trial, pembrolizumab, an anti-PD1 (programmed cell death 1) antibody, showed a survival benefit in second line metastatic urothelial cancer and should be the new standard of care. In patients who are cisplatin ineligible checkpoint can be used in first line, but no phase III data are available.

(BELG J MED ONCOL 2018;12(5):212–217)

Immuno-oncology in transitional cell Carcinoma

Immunotherapy has been used in the treatment of localised, high-risk transitional cell carcinoma. Bacillus of Calmette-Guérin therapy is a standard treatment for patients with non-invasive transitional cell carcinoma with bad prognostic factors (high-grade pTa; carcinoma in situ) and early stage invasive bladder cancer (pT1) after transurethral resection of the bladder. Recently, based on phase II trials, atezolizumab, an inhibitor of PD-L1, and nivolumab, an inhibitor of PD1, have been registered for the treatment of patients with metastatic transitional cell carcinoma progressing after a platinum-based chemotherapy for metastatic disease. Pembrolizumab, a monoclonal antibody against programmed death receptor-1 was registered based on a phase III trial in this setting resulting in a survival benefit compared to second-line chemotherapy. Predictive markers are being explored for a better patient selection for the treatment of transitional cell carcinoma.

(BELG J MED ONCOL 2018;12(5):218–222)

Targeting driver mutations in non-small-cell lung cancer, beyond the usual suspects (EGFR and ALK)

In the last decade, systemic treatment for non-small-cell lung cancer has undergone an unprecedented change because of new targeted therapies and the introduction of immunotherapy. Advances in the understanding of lung cancer biology have led to the discovery of several oncogenic driver genes and the development of drugs that target driver mutations, according to the strategy of ‘personalised therapy’. The bestknown alterations are epidermal growth factor mutations and anaplastic lymphoma kinase rearrangements, but the improvement in genomic technologies and the continuous research in this area have led to the identification of new druggable targets. This is a comprehensive overview focused on the development of targeted therapies and their mechanisms of action.

(BELG J MED ONCOL 2018;12(5):223–232)

Brain metastases: The evolving role of whole-brain radiotherapy

Over the last decade the use of whole-brain radiotherapy has decreased due to therapeutic advances, as well as in systemic treatment as in radiotherapy, but also due to a growing concern about neurocognitive failure in long-term survivors.

In patients with good prognostic factors (defined by recursive partitioning analysis or disease specific-graded prognostic assessment) and with limited brain metastases (excluding histologies s.a. SCLC, germ cell tumours, lymphomas and leukaemias), there is a trend to defer WBRT and only perform localised treatment (surgery, radiosurgery, stereotactic fractionated radiotherapy) with close follow up.

WBRT is still an option in better prognostic patients with higher intracranial tumour burden. When patients have a poor performance status, best supportive care is an equally valid option.

(BELG J MED ONCOL 2018:12(3):103–109)

The role of chemoradiotherapy in elderly patients with locoregionally advanced head and neck cancer

Paralleled by rising cancer burden, recent global demographic changes have been marked by a constantly growing number of people aged 65 or more. In the United States, presently 54% of malignant head and neck cancer cases occur in the geriatric population, and by 2030, this proportion is expected to attain 66%. Despite the obvious importance of addressing specific needs of elderly patients, these individuals have often been undertreated and refrained from geriatric assessment in clinical practices and underrepresented in prospective trials. Unfortunately, many health care professionals still believe that older patients cannot tolerate intensified treatment regimens. In this paper, we focused on concurrent chemoradiation as definitive or post-operative treatment in locoregionally advanced squamous cell carcinoma of the head and neck. Although confirmatory data from large randomised phase III trials conducted in the elderly are lacking, available evidence from meta-analyses of prospective trials and retrospective reviews of population-based cross-sectional registries indirectly support this approach, primarily in the definitive treatment setting. However, irrespective of calendar age, distinction between fit and frail senior patients is of paramount priority. In this respect, several geriatric screening tools have been developed for use by practicing physicians to help select which patients need a comprehensive geriatric assessment, who requires a specific examination only (e.g. focused on certain comorbid conditions, cognition, nutritional status, social support, or psychological state), and where no further testing is warranted.

(BELG J MED ONCOL 2018;12(3):110–117)

Brain metastases: Systemic treatment approach in 2017

This review proposes to go through reasonable systemic therapy options in brain metastases, notably immune checkpoint inhibitors and oncogen-driven targeted therapies. We deliberately focus on drugs currently available in Belgium in clinical practice. In the large majority of cases, clinical trials – in particular registration trials – exclude patients with brain metastases. Therefore we have to deal with small size non-randomised phase II trials or retrospective analysis with the known caveats of highly selected patients and numerous biases.

(BELG J MED ONCOL 2018:12(3):96–102)