T. Feys MBA, MSc

Sustained survival benefit with tremelimumab and durvalumab as first line treatment for patients with advanced hepatocellular carcinoma: 4-year data from the phase III HIMALAYA trial

Combining EGFR-TKIs and chemotherapy in patients with advanced non-small cell lung cancer: time for a new standard of care?

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.

KRAS mutations: finally a druggable target in cancer?

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 KRAS^G12C. This mini-review will provide an overview of the clinical trial data with these KRAS^G12C inhibitors and will take a brief look at a number of other selective KRAS inhibitors.

Optimising outcomes in BRAF-mutant melanoma: sequencing or combining?

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.

Journal Scan

In this section of the BJMO, we aim to provide a snapshot of pivotal studies published in recent issues of the most important international journals focusing on oncology. Importantly, the selection of the studies discussed here is the sole responsibility of the publisher and was not influenced by third parties. Do you miss an important study, or did you read a hidden jewel that deserves to be shared with your colleagues? Please, let us know (editor@bjmo.be) and we will make sure to include it in the journal scan section of the next BJMO issue.

(BELG J MED ONCOL 2023;17(6):239–44)

Highlights in lung cancer

SUMMARY

The most important lung cancer news at ASCO 2023 came from the ADAURA trial, showing a significant overall survival (OS) benefit from adjuvant osimertinib in patients with early-stage EGFR-mutant non-small cell lung cancer (NSCLC). Also in the early-stage setting, three different studies showed the clinical potential of using immunotherapy in the (neo)adjuvant treatment of non-oncogene-driven NSCLC patients. In the advanced setting, KEYNOTE-789 did not show a benefit with the addition of pembrolizumab to chemotherapy in EGFR-mutant advanced NSCLC patients progressing on first-line anti-EGFR TKI therapy. In the same setting, two new EGFR TKIs (BLU-945 and sunvozertinib) yielded promising results. Finally, retrospective data brought further insights into the optimal treatment duration of immunotherapy and on the use of chemoimmunotherapy in older NSCLC patients.

(Belg J Med Oncol 2023;17(5):183–6)

Reflex testing for mutations in patients with early-stage non-small cell lung cancer: practical implications from ADAURA

SUMMARY

Targeted therapies against activating EGFR mutations stood at the cradle of the personalised treatment revolution for patients with advanced non-small cell lung cancer (NSCLC). Since then, molecular testing for EGFR mutations and many other oncogenic drivers has become part of the routine diagnostic work-up for patients with advanced NSCLC. Recently, the phase III ADAURA trial showed that the EGFR TKI osimertinib also induces a significant overall survival benefit in the adjuvant treatment of patients with early-stage NSCLC, instigating a new wave in this personalised treatment revolution. Based on these results, routine EGFR mutation testing should be expanded to also include early-stage NSCLC patients. In this, a reflex testing strategy is preferred as it reduces turnaround times and standardises the ordering of biomarker tests to ensure that more patients are being tested.