Articles

Immune checkpoint inhibitor therapy and COVID-19: What do we know so far?

BJMO - 2020, issue Special, december 2020

T. Rawson MSc, Tom Feys MBA, MSc

The ongoing coronavirus pandemic has a direct impact on all medical specialities, and oncology is definitely no exception to this. In any case, COVID-19 represents a significant clinical threat to patients with cancer. In fact, recent data show that Belgian cancer patients who were admitted to secondary care with a COVID-19 infection, were 34% more likely to die within 30 days of admission, compared to COVID-19 patients without an active solid tumour.1 It is well-established that almost all therapeutic modalities used in cancer patients directly interact with the immune system. In this light, concerns have been raised on the potential impact of anticancer therapy on the course of a COVID-19 infection. These concerns were most pronounced in relation to the role of immunomodulatory drugs, such as immune checkpoint inhibitors (ICI) in COVID-19 infected patients. These agents directly bind to lymphocytes and subsequently exhibit pleiotropic effects on the activity of a patient’s immune system. As such, it is no surprise that there is great interest in the potential interaction between ICI therapies and the course of a COVID-19 infection.

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Immunotherapy for the treatment of triple-negative breast cancer

BJMO - 2020, issue Special, december 2020

J. Blokken PhD, PharmD, Tom Feys MBA, MSc, K. Punie MD

While immune checkpoint inhibitors (ICIs) demonstrated a convincing efficacy with durable responses in many cancer types, the single agent efficacy of ICIs in patients with advanced triple-negative breast cancer (TNBC) proved to be low. In a successful attempt to boost this clinical activity, ICIs were subsequently combined with chemotherapy in patients with metastatic TNBC. Following the positive results in the metastatic setting, ICIs are now also under evaluation in combination with neoadjuvant chemotherapy in patients with early TNBC. This review provides an overview of the results obtained with ICI in TNBC, from the disappointing results with ICI monotherapy, over the emerging data with ICI-chemotherapy combinations in the neoadjuvant setting to the pivotal, practice-changing results obtained with atezolizumab and atezolizumab in combination with chemotherapy in metastatic TNBC patients.

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The emerging role of immunotherapy in small-cell lung cancer

BJMO - 2020, issue Special, december 2020

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

In contrast to the impressive improvements that were made in the treatment of patients with non-small cell lung cancer, the treatment for patients with small-cell lung cancer (SCLC) remained largely unchanged during the past three decades. More recently, however, immune checkpoint inhibitors have been gaining momentum in this setting. In Belgium, patients with extensive stage (ES) SCLC now have the choice between two effective treatment regimens combining an immune checkpoint inhibitor with chemotherapy. In addition to this, several other immunotherapy-based therapies are being scrutinised in clinical trials with ES SCLC patients.

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Synergism between CTLA-4 and PD-(L)1 inhibition: the nivolumab-ipilimumab story

BJMO - 2020, issue Special, december 2020

J. Blokken PhD, PharmD, Tom Feys MBA, MSc, P. Coulie MD, PhD

In recent years, the approval of anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1) antibodies have led to significant improvements in disease outcomes for various cancers. Despite their long-term durable efficacy, the responses to immune checkpoint blockade are limited to a minority of patients. In an attempt to overcome this, the combination of CTLA-4 and PD-1 inhibitors is gaining momentum as a rational approach to improve outcomes.1 This review describes the mechanism of action of both nivolumab and ipilimumab and discusses how the combined use of both drugs leads to potential synergism. The final part of the article assesses the extent to which this theoretical synergism is translated into a clinical benefit for cancer patients.

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Immunotherapy as frontline treatment for advanced hepatocellular cancer

BJMO - 2020, issue Special, december 2020

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

For more than a decade, systemic treatment of advanced hepatocellular carcinoma (HCC) remained limited to the use of the tyrosine kinase inhibitor sorafenib, with lenvatinib being a non-inferior alternative to this standard of care. Recently, however, results of the phase III IMbrave 150 trial, demonstrated that the combination of atezolizumab and bevacizumab is associated with a significantly better progression-free and overall survival than sorafenib in the frontline treatment of patients with advanced HCC. This finding will have a dramatic impact on the treatment paradigm for these patients. In addition to atezolizumab-bevacizumab, several other immunotherapy-based treatment regimens are being evaluated in the treatment of advanced HCC.

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Highlights in gynaecological cancers

BJMO - volume 14, issue 8, december 2020

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

In this overview, the key highlights from ESMO 2020 with respect to gynaecological cancers will be discussed. In advanced endometrial cancers, data were presented on the use of letrozole in combination with palbociclib. In addition, to this, promising clinical efficacy was seen for the antibody-drug conjugate tisotumab vedotin in the treatment of patient with recurrent or metastatic cervical cancer. Also in cervical cancer, a study was presented on the optimal management of cervical cancer patients with intraoperatively detected positive pelvic lymph nodes. In ovarian cancers, several updates were presented of pivotal trials evaluating PARP inhibitors. In addition, results if the phase III INOVATYON trial indicate that platinum-based regimens should remain the standard of care for patients with recurrent ovarian cancer who experienced disease progression within six-twelve months after their last line of platinum-based therapy. Finally, results were presented of the IMagyn050 trial assessing the efficacy and safety of bevacizumab in combination with atezolizumab in the treatment of patients newly diagnosed stage III-IV ovarian cancer.

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Highlights in melanoma

BJMO - volume 14, issue 8, december 2020

J. Blokken PhD, PharmD, Tom Feys MBA, MSc, B. Neyns MD, PhD

At ESMO 2020, most attention in the melanoma field went to studies addressing the benefit of immunotherapy, alone or in combination with other drugs. First of all, updates on the use of immunotherapy in the adjuvant setting were provided for the Keynote-054 and the CheckMate 238 trials. In the advanced melanoma setting, several studies investigating combinations of immunotherapy with targeted agents will be addressed. In addition to this, the ILLUMINATE-204 trial investigates the potential of combining immunotherapy with intratumoral therapy. Similarly, a second study describes the value of local therapy in the treatment of solitary melanoma after progression upon checkpoint inhibitors. Finally, vaccination strategies with an IDO/ PD-L1 peptide vaccine and adjuvant dendritic cell vaccination will be discussed.

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