BJMO - 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
Read moreBJMO - volume 11, issue 9, february 2017
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 to 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 successes with immune checkpoint inhibition in stage IV NSCLC formed the basis to also study these agents in the curative NSCLC setting. Several studies are underway evaluating the potential of adjuvant immune checkpoint inhibition in stage II and IIIA disease and promising data have also been generated in the pre-operative setting. In addition to that, immune checkpoint inhibition is also being studied as consolidation treatment following chemoradiotherapy in locally advanced, unresectable NSCLC. The PACIFIC trial forms the first of these studies to yield results and showed that the PD-L1 inhibitor durvalumab significantly prolongs the progression-free survival (PFS) compared to placebo in patients with locally advanced, unresectable stage III NSCLC. More mature (overall survival, OS) results of this study are eagerly awaited as are the results of the other clinical studies evaluating immune checkpoint inhibitors in the curative NSCLC setting.
Read moreBJMO - volume 11, issue 9, february 2017
D. Gullentops , E. Wauters MD, PhD, J. Vansteenkiste MD, PhD
Since its start in 2009, immunotherapy with immune checkpoint inhibitors has become a hot topic in respiratory oncology. Randomized controlled trials have proven the superiority of immune checkpoint inhibitor therapy versus standard chemotherapy in advanced non-small cell lung cancer (NSCLC). PD-L1 immunohistochemistry (IHC) is so far the most commonly implemented predictive biomarker in the selection of optimal candidates for immunotherapy. Immunotherapy with pembrolizumab is approved in first-line for advanced NSCLC with a PD-L1 expression on >50% of tumor cells, and after at least one prior chemotherapy regimen in case of PD-L1 expression of >1%. Treatment with nivolumab or with atezolizumab is approved for advanced NSCLC after prior chemotherapy, irrespective of the PD-L1 status. Since PD-L1 expression does not always correlate with treatment efficacy, other biomarkers are under investigation. Tumor mutational burden (which correlates clinically with smoking status) and CD8 tumor-infiltrating lymphocytes are associated with increased responsiveness to PD-L1 inhibition, and thus are other promising predictive biomarkers. NSCLC with molecular drivers on the contrary is preferably treated with tyrosine kinase inhibitors (TKIs) rather than immunotherapy due to lower response rates, even in case of high PD-L1 expression. Immunotherapy and other therapeutic modalities (chemotherapy, radiotherapy, TKIs) might work in synergy. The results of the first prospective trials with combination therapy were recently published, and many others are to be expected.
Read moreBJMO - volume 11, issue 9, february 2017
B. Neyns MD, PhD, G. Awada MD, A. Rogiers MD
Over the past 10 years, several effective new therapies have been developed for patients with advanced melanoma. Since 2010, the primary endpoint of every major phase III trial in this setting has been met, revolutionizing the treatment options and survival for patients with unresectable advanced melanoma. With increasing numbers of patients experiencing durable remissions with these agents, even without continuing therapy, the issue of melanoma survival care becomes of relevance to more patients than ever before.
Read moreBJMO - volume 11, issue 9, february 2017
L. Brochez MD, PhD, I. Chevolet MD, PhD, A. Meireson , V. Kruse MD, PhD
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. This manuscript reviews the currently available data on the role of IDO in cancer and the current results obtained with IDO inhibition in clinical trials in humans. Preliminary results with IDO inhibitors, usually combined with other anti-cancer drugs, seem encouraging. Further studies are needed to clarify the conditions in which IDO inhibitors can be of value as an anti-cancer strategy. In addition, further research should address whether the expression of IDO in tissue or blood can be a marker to select patients who can benefit most from IDO inhibition.
Read moreBJMO - volume 10, issue 3, october 2016
Tom Feys MBA, MSc
The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoints are negative regulators of the T-cell immune function. Inhibition of these targets, resulting in an increased activation of the immune system, has led to new immunotherapies for melanoma, non–small cell lung cancer, and other cancers. To set the stage for the impressive clinical data that have been produced with these agents, this introductory article will describe the similarities and differences of both pathways and will touch upon the implications of their inhibition.
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