SPECIAL

Immunotherapy for ovarian cancer: a challenging endeavor

BJMO - 2022, issue Immuno-Oncology Special, december 2022

T. Feys MBA, MSc

Ovarian cancer (OC) remains to be one of the most common gynecological malignancies and is characterized by a high mortality and a poor prognosis. Cytoreductive surgery and chemotherapy remain the backbone of the OC treatment, but despite this strategy most women will experience disease recurrence. For these patients there is a large unmet need for more effective therapies. Despite the compelling evidence for the fact that OC is an immunogenic tumor, studies evaluating immune checkpoint inhibitors have yielded largely disappointing results. Several therapeutic strategies are currently being studied to boost response rates to anti-PD1/PD-L1, including the addition of chemotherapy, anti-angiogenic agents, PARP inhibitors, or other immune checkpoint inhibitors. In addition to this, other immunotherapeutic approaches such as adoptive T-cell therapy, vaccines and therapeutic targeting of myeloid immune checkpoints such as the “don’t eat me” signal CD47 are also being investigated in OC. While several of these options are promising, large controlled randomized studies are still needed to implement new immunotherapeutic options into clinical practice.

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Immune checkpoint inhibition for pancreatic cancer: is there light at the end of the tunnel?

BJMO - 2022, issue Immuno-Oncology Special, december 2022

T. Feys MBA, MSc

Pancreatic adenocarcinoma (PDAC) continues to be one of the most lethal cancers. In recent years, immunotherapy using immune checkpoint inhibitors (ICIs) resulted in dramatic clinical benefits in many solid tumor types. However, PDAC patients are yet to experience the potential benefits of this treatment strategy. This article will provide a brief overview of the available data obtained with ICI-based treatments in patients with advanced PDAC. These studies illustrate that PDACs are inherently immune-cold tumors who are largely refractory to ICI-based therapy in clinical trials. Understanding and overcoming the current failures of immunotherapy through elucidating resistance mechanisms and developing novel therapeutic approaches are essential to harness the potential durable benefits of immune-modulating therapy in this setting.

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The evolving role of immunotherapy in the treatment paradigm for patients with small-cell lung cancer

BJMO - 2022, issue Immuno-Oncology Special, december 2022

T. Feys MBA, MSc

Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases and is characterized by an aggressive disease course and a particularly poor prognosis. For decades, the best available systemic therapy for patients with extensive-stage (ES) SCLC consisted of platinum-etoposide chemotherapy. In recent years, however, extensive-stage (ES) SCLC has become the second thoracic malignancy in which immune checkpoint inhibition (ICI) proved to prolong the survival of patients. In fact, the phase III CASPIAN and IMpower133 studies showed that the addition of respectively durvalumab and atezolizumab to chemotherapy significantly prolongs the overall survival (OS) of patients with ES-SCLC. The results of these studies quickly established chemo-immunotherapy as the preferred initial treatment for these patients. Nevertheless, the benefit provided by ICI remains to be limited to a proportion of patients and most patients eventually relapse. Therefore, innovative treatment strategies and ICI-based combinations are currently under investigation to further improve the prognosis of patients with ES-SCLC. In addition, studies are looking into the potential of ICI in patients with limited stage (LS) disease.

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Immunotherapy for non-metastatic non-small-cell lung cancer: available data and future perspectives

BJMO - 2022, issue Immuno-Oncology Special, december 2022

T. Feys MBA, MSc

Over the last decade, immune checkpoint inhibition (ICI) has dramatically changed the treatment landscape for patients with metastatic non-small-cell lung cancer (NSCLC). The success of ICI-based therapy in the metastatic setting fed the interest to also evaluate the potential of immunotherapy in earlier NSCLC disease stages. This article will provide a brief overview of the available, practice-changing data with ICI-based therapy in the neoadjuvant and adjuvant treatment for patients with early-stage NSCLC. Recently, these data led to the EMA approval of atezolizumab as monotherapy in the adjuvant treatment of selected early-stage NSCLC patients. In addition, EMA approval is currently also being sought for the combination of nivolumab and chemotherapy as neoadjuvant therapy for patients with resectable NSCLC. In addition to the results in the (neo)adjuvant setting, this article will also address the clinical basis for ICI-based therapy in unresectable,locally-advanced NSCLC.

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The KRAS oncogene: a long and winding road to druggability

BJMO - 2022, issue Targeted Therapy Special, november 2022

J. Blokken PhD, PharmD, T. Feys MBA, MSc

The Kirsten rat sarcoma viral oncogene homolog (KRAS) is mutated in about a quarter of all human cancers and is at the centre of several pathways involved in tumorigenesis. As such, novel therapeutic strategies that can target this oncoprotein are potentially extremely valuable. However, since its discovery as on oncogene, almost four decades have gone by without any major breakthrough in the therapeutic targeting of mutant KRAS. In recent years, however, we are finally witnessing a paradigm shift with the discovery of druggable pockets on KRAS and the clinical activity of covalent KRASG12C inhibitors such as sotorasib and adagrasib.

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Antibody-drug conjugates in the treatment of advanced breast cancer

BJMO - 2022, issue Targeted Therapy Special, november 2022

T. Feys MBA, MSc

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. In 2013, the human epidermal growth factor receptor 2 (HER2)-targeted ADC ado-trastuzumab emtansine (T-DM1) entered the treatment arsenal for patients with metastatic breast cancer (BC), making it the first ADC to be approved for the treatment of a solid tumor. The pace of ADC development for solid tumors has since increased dramatically, with currently more than 100 ADCs being investigated in clinical trials. Specifically in breast cancer, there are now 3 EMA-approved ADCs: T-DM1, trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG). This article will briefly touch upon the key components and mode of action of ADCs after which the clinical experience with the EMA-approved ADCs in breast cancer will be discussed.

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Rapid PCR testing as adjunct to next-generation sequencing for the detection of alterations in patients with non-small-cell lung cancer

BJMO - 2022, issue Targeted Therapy Special, november 2022

T. Feys MBA, MSc

Next-generation sequencing (NGS) is increasingly replacing single gene assays in the screening for therapeutic biomarkers in patients with NSCLC. While NGS has the clear advantage that it can detect all targetable oncogenic driver alterations simultaneously, this technique does come with the risk for a longer turnaround time, in part as a result of the centralized way in which this testing is often organized. However, with a delayed test result, you risk that some patients with a high disease burden miss the opportunity to be treated with a specific targeted therapy, or even die before the NGS result comes in. To mitigate this risk, it may be interesting to adopt a rapid PCR-based testing strategy for selected oncogenic driver mutations in parallel to broad NGS testing.

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