T. Feys MBA, MSc

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.

Highlights in melanoma

SUMMARY

At ASCO 2023, updated distant metastasis-free survival data from KEYNOTE-716 trial provided additional support for the use of adjuvant pembrolizumab in Stage IIB/IIC melanoma. While a biomarker analysis of the CheckMate 76K study provides some insights into biomarkers that correlate with a greater benefit from adjuvant nivolumab, these factors unfortunately do not allow a selection of the most suitable patients for this therapy in daily practice. In addition to this, promising data were generated with a new immune-oncology strategy combining a personalised therapeutic RNA vaccine and pembrolizumab in patients with stage III melanoma. Finally, a two-year update of the RELATIVITY-047 trial confirmed the benefit of nivolumab plus relatlimab over nivolumab alone in patients with previously untreated, unresectable, or metastatic melanoma.

(Belg J Med Oncol 2023;17(5):89–92)

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)