BJMO - 2023, issue Special, november 2023
T. Feys MBA, MSc
The introduction of tyrosine kinase inhibitors (TKIs) that specifically target mutant EGFR marked the start of the personalized medicine revolution in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Nowadays, osimertinib has become the standard of care first line treatment in this setting. However, also with this third generation EGFR-TKI, patients will eventually relapse, underscoring the need for alternative treatment strategies that can prevent or delay treatment resistance. In this respect, several studies assessing first- and second-generation EGFR-TKIs indicated a benefit of combining these agents with chemotherapy in patients with EGFR-mutant NSCLC. More recently, data from the phase III FLAURA-2 study showed a statistically significant and clinically meaningful improvement in progression-free survival with the first line combination of osimertinib and platinum-pemetrexed over osimertinib monotherapy, with a manageable safety profile. This mini review provides an overview of the clinical data with EGFR-TKI plus chemotherapy combinations in the treatment of patients with previously untreated, advanced EGFR-mutant NSCLC, with particular attention for the FLAURA-2 data.
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J. Blokken PhD, PharmD
Cholangiocarcinoma (CCA) is the second most common primary liver cancer and accounts for approximately 10–15% of all primary liver cancers. CCA is subdivided into intrahepatic CCA (iCCA), arising from bile ductules proximal to the second-order bile ducts; perihilar CCA (pCCA), arising in the right and/or left hepatic duct and/or at their junction; and distal CCA (dCCA), arising from the epithelium distal to the insertion of the cystic duct. pCCA and dCCA are collectively referred to extrahepatic CCA (eCCA). For patients with early-stage CCA, the treatment usually consists of a surgical resection followed by adjuvant chemotherapy, while systemic chemotherapy is the standard first-line treatment for patients with advanced stage disease. However, given the fact that nearly 40% of patients with biliary tract cancer harbour genetic alterations which are potential targets for precision medicine, molecular analysis should be carried out before or during firstline therapy to evaluate options for second and higher lines of treatment as early as possible in advanced disease.1 This review aims to discuss the most promising therapeutic molecular targets for CCA and the targeted agents that are available in this setting.
Read moreBJMO - 2023, issue Special, november 2023
T. Feys MBA, MSc
KRAS is the most frequently mutated oncogene in human malignancies and is therefore often considered as the ‘holy grail’ of targeted cancer therapies. For many years, however, investigators failed to develop effective selective inhibitors of mutant KRAS. More recently, progress has been made with the development of specific inhibitors of KRASG12C. This mini-review will provide an overview of the clinical trial data with these KRASG12C inhibitors and will take a brief look at a number of other selective KRAS inhibitors.
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A. Enguita PhD, T. Feys MBA, MSc
Over the last decades, immune checkpoint inhibitors (ICI) and dual BRAF/MEK inhibition have transformed the treatment landscape for patients with advanced melanoma. However, the availability of two effective treatment strategies for patients with BRAF-mutant advanced melanoma brings about the question of the optimal treatment sequence for patients. This article summarizes the currently available evidence on the efficacy and safety of sequential immunotherapy with targeted therapy in this setting.
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