Articles

Integrating immunotherapy in the treatment paradigm for early-stage non-small cell lung cancer

BJMO - 2021, issue BJMO IO Special, december 2021

T. Feys MSc, MBA

Immune checkpoint inhibition (ICI) marked the start of a new era in the treatment of advanced non-small cell lung cancer (NSCLC), inducing a durable response in a substantial proportion of patients. The success of ICI in the advanced setting spurred interest to also examine the potential of this treatment modality in patients with early-stage NSCLC. The first success story in this respect came from the phase III PACIFIC trial, establishing consolidation therapy with durvalumab after chemoradiation as the new standard of care for patients with inoperable, locally advanced NSCLC. More recently, ICI also yielded promising results in patients with resectable NSCLC. In fact, the IMpower010 trial showed that adjuvant atezolizumab after 4-cycles of platinumbased chemotherapy significantly improves the disease-free survival (DFS) compared to best supportive care in patients with stage II-IIIA NSCLC. In addition to this, other studies suggest that neoadjuvant treatment with ICI might result in substantial major pathologic response and pathologic complete response rates, and high rates of R0 resection without a significant delay in the time to surgery.

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Highlights in gynaecological oncology

BJMO - volume 15, issue 8, december 2021

A. Enguita PhD, T. Feys MSc, MBA

The 2021 annual ESMO meeting featured several presentations with the potential to shift the standard of care in gynaecological cancers. In cervical cancer, Keynote-826 identified pembrolizumab + chemotherapy (with or without bevacizumab) as a potential new standard of care for patients with persistent, recurrent, or metastatic cervical cancer. In addition, also the antibody drug conjugate tisotumab vedotin showed encouraging and durable anti-tumour activity in this setting. In the field of the ovarian cancer, PARP inhibition again walked away with most of the attention, but also the glucocorticoid receptor modulator relacorilant and combination therapy with the immune checkpoint inhibitor atezolizumab and bevacizumab yielded interesting data. Also for patients with advanced endometrial cancer, ESMO 2021 proved to be of interest, with important updates on the use of pembrolizumab in this setting.

(BELG J MED ONCOL 2021;15(8):428–35)

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Highlights in respiratory oncology

BJMO - volume 15, issue 8, december 2021

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

At this year’s ESMO meeting, much of the attention in the field of lung cancer went to early-stage nonsmall cell lung cancer (NSCLC) with interesting results from the Lung Art, COAST, GEMSTONE-301 and IMpower010 trials. For metastatic NSCLC, immunotherapy again walked away with much of the attention. In addition to this, several studies investigated the potential of combining anti-EGFR and anti-angiogenic agents, while others investigated novel targeted agents, including trastuzumab deruxtecan, poziotinib, plinabulin and datopotamab deruxtecan. Finally, we will highlight the most interesting results in other thoracic malignancies, including malignant pleural mesothelioma, extensive-stage small cell lung cancer, thymoma and thymic carcinoma.

(BELG J MED ONCOL 2021;15(8):406–14)

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Highlights in breast cancer

BJMO - volume 15, issue 8, december 2021

A.M. Dekker MSc, T. Feys MSc, MBA, K. Punie MD, H. Wildiers MD, PhD

At this year’s annual meeting of the European Society of Medical Oncology (ESMO) experts shared some game-changing data for the treatment of breast cancer (BC). In advanced HER2+ metastatic breast cancer m(BC), the DESTINY-Breast03 trial performed a head-to-head comparison of T-DM1 and trastuzumab deruxtecan (T-Dxd) following initial treatment with trastuzumab and a taxane, showing a major PFS benefit for T-DXd without major toxicity issues, establishing T-DXd as the new standard of care in this setting. In luminal breast cancer, the final analysis of the GIM-4 study supports the use of 7 years instead of 5 years adjuvant endocrine therapy in postmenopausal patients with hormone receptor positive (HR+)/HER2- early BC. For advanced stage HR+/HER2- BC, the MONALEESA-2 study shows >1y OS benefit when adding the CDK4/6 inhibitor ribociclib to letrozole as first-line treatment. Finally, in triple negative breast cancer (TNBC), the phase III BrighTNess study showed that addition of carboplatin to neoadjuvant chemotherapy provides long term EFS benefit. In metastatic TNBC, OS data of KEYNOTE-355 further support the use of first-line pembrolizumab plus chemotherapy in advanced PD-L1+ TNBC.

(BELG J MED ONCOL 2021;15(8):390–7)

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The role of HER2-targeted therapy in metastatic gastrointestinal cancer: gastric cancer (and beyond)

BJMO - 2021, issue Special, november 2021

T. Feys MSc, MBA

Molecular targeted therapy of cancer has long been the focus of clinicians, with the human epidermal growth factor receptor-2 (HER2) signalling pathway being one of the most popular targets. However, in contrast to the plethora of anti-HER2 agents that have entered the breast cancer treatment paradigm, trastuzumab remains the only anti-HER2 drug that is approved for the first-line treatment of HER2 positive advanced gastric cancer. Recently, however, promising data are emerging with new anti-HER2 agents, including antibody-drug-conjugates (ADC) and bispecific antigens. In addition, also the combination of anti-HER2 therapy with immune checkpoint inhibition holds lots of promise for the treatment of HER2-positive stomach cancer. Despite being standard of care in the treatment of HER2-positive gastric cancer, the role of HER2 as a therapeutic target is far less established in other gastrointestinal malignancies. However, promising data with the ADC trastuzumab-deruxtecan are emerging in colorectal cancer and also in biliary tract cancer phase I studies start to point towards a potential role for HER2 targeting.

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Targeted therapy making its move in early-stage EGFR-mutant NSCLC

BJMO - 2021, issue Special, november 2021

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

Approximately 25% of patients with non-small cell lung cancer (NSCLC) are being diagnosed in an early stage of the disease. Even though these patients are eligible for radical surgery, the five-year survival rates for fully resected early-stage NSCLC remains disappointing. In fact, for patients who receive adjuvant chemotherapy after surgery, recurrence rates are high, with approximately half of patients suffering from disease relapse. The design of molecularly oriented studies and the availability of novel potent and less toxic targeted agents paved the way for the evaluation of these drugs in the (neo)adjuvant setting for patients with early-stage NSCLC harbouring oncogenic driver mutations. Here we summarise the results obtained with EGFR-targeted drugs in early-stage NSCLC.

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Treatment sequencing in patients with advanced, BRAF-mutant melanoma

BJMO - 2021, issue Special, november 2021

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

Over the last decade, the introduction of immune checkpoint inhibitors and targeted agents inhibiting BRAF, and MEK signal transduction pathways revolutionised the treatment paradigm for patients with metastatic melanoma. However, to date there is still no consensus on the optimal treatment sequence in BRAF-mutant metastatic melanoma. In the absence of prospective, randomised data, the treatment choice in clinical practice is mainly driven by patient characteristics. More recently, clinical trials are assessing the optimal treatment sequence of targeted therapy and immunotherapy, while other studies are looking into the potential of combining both treatment modalities in first-line.

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