BJMO - volume 12, issue 9, february 2018
P. Szturz MD , J.B. Vermorken MD, PhD
Squamous cell carcinoma of the head and neck (SCCHN) has recently expanded the growing range of oncologic diseases successfully treated with immune-modulating agents. With the origins dating back to the nineteenth century, the concept of immunotherapy was repeatedly revisited and refined but also rejected and criticized. Currently, its armamentarium comprises tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating antibodies. Among these approaches it has been the latter one drawing major attention from healthcare professionals. Nivolumab and pembrolizumab are monoclonal immunoglobulins directed against programmed cell death protein-1 (PD-1), an immune-checkpoint negatively regulating T-cells. In second-line recurrent and/or metastatic SCCHN, two phase III studies demonstrated meaningful clinical benefit achieved by these drugs, dubbed checkpoint inhibitors, compared with standard monotherapy (methotrexate, docetaxel, or cetuximab). In the CheckMate-141 trial, nivolumab significantly improved median overall survival (OS) from 5.1 to 7.5 months. A similar benefit achieved by pembrolizumab in KEYNOTE-040 fell short of statistical significance (8.4 vs. 6.9 months), probably due to post-study immune-checkpoint therapy leading to a better-than-expected survival in the control arm. However, the classical outcome measures do not fully capture the exceptional activity of these agents. Apart from low frequency of severe adverse events (13% vs. 35% with standard therapy), these antibodies can induce durable tumour responses and retain activity even after several previous chemotherapy lines. With their advent in first-line palliative regimens and protocols for locally advanced disease, further progress is expected. Reliable predictive biomarkers are urgently needed, and several candidates are being evaluated. Among them, tumour mutational burden and gut microbiota offer an innovative approach to biomarker-enrichment strategies.
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C. Boeckx PhD, E. Smits PhD, J. Jacobs PhD
Nowadays, PD-L1/PD-1 immune checkpoint inhibitors have become a key part of the clinical management of cancer. Improving our understanding of anti-cancer immune response, which is influenced by a complex set of tumour, host and environment factors, will further broaden the clinical applicability of these treatments. In this review, we discuss several approaches to evaluate the tumour microenvironment (TME) in clinical practice as well as a view on future predictive biomarkers for cancer immunotherapy.
Read moreBJMO - volume 12, issue 9, february 2018
V. Geldhof MD, PhD, K. Punie MD, H. Wildiers MD, PhD
Triple negative breast cancers pose an important challenge both for patients and their clinicians due to their aggressive disease course, poor long-term survival and lack of effective systemic treatment options. Recent scientific advances show that the adaptive immune system harbors the intrinsic capacity to eradicate cancer, generally through mechanisms that involve cytotoxic T-cells. Immune checkpoint inhibition boosts the host-anti-tumor response in many solid tumors, including breast cancer. However, cancer cells acquire ways to evade immunosurveillance and intra-tumoral T-cells are often functionally impaired, resulting in overt clinical cancer. Interestingly, the efficacy of immune checkpoint inhibition appears to correlate with tumor immunogenicity and the tumor mutational burden. Triple negative breast cancer has the highest tumor mutational burden of all breast cancer subtypes and therefore is believed to be the most immunogenic subtype. For this reason, clinical trials to date mainly focus on this specific subtype. Here, we review the accumulating evidence for immune checkpoint blockade in triple negative breast cancer.
Read moreBJMO - volume 12, issue 9, february 2018
S. Aspeslagh , V. Kruse MD, PhD, E. De Langhe , P. Jacques , O. Malaise , D. Elewaut , B. Lauwerys , R. Wittoek , Y. Piette , B. Neyns MD, PhD
Immunotherapy has become a standard of care for patients with many different advanced solid tumors. However, boosting the immune system can induce immune related side effects, referred to as “immune-related adverse events” (irAEs). Because oncologists are not always familiar with these inflammatory autoimmune syndromes, the BSMO immunotaskforce has launched the immunomanager website which summarizes the treatment options for the most frequent irAEs including endocrine (e.g. hypo- and hyperthyroidism), digestive (e.g. colitis), pneumological (e.g. pneumonitis), dermatological and other types of irAEs. In the near future, the BSMO immunotaskforce plans to review these recommendations with Belgian organ specialists and their associations. We believe that through collaborations between organ specialists and oncologists we will be able to establish better recommendations, resulting in a better outcome for cancer patients who develop an irAE during immunotherapy.
Read moreBJMO - volume 12, issue 9, february 2018
S. De Keukeleire MSc, V. Kruse MD, PhD, S. Rottey MD, PhD
Immune checkpoint inhibition (ICI) has been acknowledged as a breakthrough treatment in multiple advanced cancer types. This is also the case in metastatic Merkel Cell Carcinoma (MCC), a disease that is historically associated with a poor prognosis. Recently, several randomized trials demonstrated superior results of ICI compared to chemotherapeutic agents in patients with metastatic MCC, with less toxicity, an increased overall survival (OS), and more durable responses. Therefore, ICI is now generally considered as a new standard treatment option in this setting.
Read moreBJMO - volume 12, issue 9, february 2018
Tom Feys MBA, MSc
The progress that has been made in the last decades in the treatment of stage IV non-small cell lung cancer (NSCLC) has overall not been translated in the curative setting of stage I to III disease. In fact, the list of failed clinical trials aimed at improving the cure rates in this setting is long. The recent successes with immune checkpoint inhibition in stage IV NSCLC formed the basis to also study these agents in the curative setting. The first clinical trials to yield results in this setting evaluate immune checkpoint inhibition as consolidation treatment following chemoradiotherapy in locally advanced, unresectable NSCLC. The PACIFIC trial demonstrated that consolidation therapy with PD-L1 inhibitor durvalumab significantly prolongs both the progression-free (PFS) and overall survival (OS) compared to placebo in patients with disease control after chemoradiotherapy for stage III unresectable NSCLC. These findings have recently led to the EMA indication of durvalumab as a treatment of locally advanced, unresectable NSCLC patients whose tumors express PD-L1 on ≥1% of tumor cells and whose disease has not progressed following platinum-based chemoradiation therapy. In addition to this, recent phase II data show that consolidation pembrolizumab following concurrent chemoradiotherapy substantially prolongs the time to metastasis or death in patients with inoperable stage III NSCLC. Finally, the phase II ETOP NICOLAS trial demonstrated that the addition of nivolumab to concurrent chemoradiotherapy is safe and tolerable in stage III NSCLC with promising efficacy signals. Together all these data support the further exploration of immune checkpoint inhibition in the curative NSCLC setting. Several trials are currently ongoing, including studies on the potential of adjuvant immune checkpoint inhibition in stage II and IIIA disease and trials in the pre-operative setting.
Read moreBJMO - volume 11, issue 9, february 2017
E. Seront MD, PhD, J.P. Machiels MD, PhD
Immunotherapy harnesses the immune system to recognize and destroy cancer cells. This review focuses on the different agents that are currently approved in genitourinary cancers and highlights promising therapeutic strategies in this field. The clinical data generated in advanced urological cancer, advanced renal cell carcinoma (RCC) and metastatic prostate cancer will be discussed
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