BJMO - volume 10, issue 3, october 2016
P. Germonpré , J. Lamont
Cancer immunotherapy consists of a number of approaches that aim to utilize the power of the immune system to combat the cancer by producing activated tumour-specific cytoxic T-cells (CTL) that are able to eradicate the antigen-bearing tumor cells. Cancer immunotherapies can be divided in (i) active immunotherapies aiming to mount an immune response to one or more tumour-associated antigens (i.e. cancer vaccines), (ii) passive immunotherapies relying on the administration of exogenously produced tumor antigen-specific lymphocytes or antibodies and (iii) immunomodulatory approaches that try to amplify the anticancer immune response by blocking the down-regulation of the adaptive immune system (i.e. checkpoint inhibitors). This brief overview will focus on those cancer immunotherapies for which survival data in lung cancer are available from large randomized controlled trials.
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J-F. Baurain MD, PhD
Cutaneous melanoma has long been one of the most aggressive forms of cancer, with limited treatment options and a very dismal prognosis. However, in recent years new strategies for treating melanoma have been introduced that significantly improve the outlook for patients with this challenging disease. One of the most important advances has been the development of immunotherapy. The better understanding of the role of the immunological system in tumor control has paved the way for strategies to enhance the immune response against cancer cells. Monoclonal antibodies (mAbs) against the immune checkpoints cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have demonstrated high activity in melanoma and other tumors. This has marked a new era in the treatment of metastatic melanoma and much research is now ongoing with other checkpoint inhibitors and investigating combinations of agents targeting different immune checkpoints.
Read moreBJMO - volume 10, issue 3, october 2016
Tom Feys MBA, MSc
The past years brought early reports suggesting that immune checkpoint inhibitors targeting PD-1 and PD-L1 are effective across a range of different cancer types, beyond melanoma and lung cancer. A particularly encouraging finding was that immunotherapy was effective against many tumors that were resistant to traditional treatments.
Read moreBJMO - volume 10, issue 3, october 2016
B. Neyns MD, PhD
The initial use of immune checkpoint blockade was mainly limited to a fraction of physicians involved in the treatment of malignant melanoma. With the proof of principle and efficacy established in this disease process, these agents were being extensively investigated in other malignancies including lung cancer, renal cell carcinoma, gastric cancer, bladder cancer, ovarian cancer, and hematologic malignancies. Early results from some of these investigations are extremely encouraging and will likely lead to more indications in addition to the approved indications for the treatment of malignant melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma. It is therefore essential that the oncology community is aware of immune-related adverse events (irAEs), to recognize them in a timely fashion and be well-versed with their management. To discuss the specific toxicity profile associated with these agents, we consulted Prof. Dr. Bart Neyns, melanoma specialist at the UZ Brussel, with a vast experience in the use of immune-checkpoint inhibitors.
Read moreBJMO - volume 10, issue 3, october 2016
P. Specenier MD, PhD
Cancer immunology is living its Golden Age.1,2 The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab (Yervoy®) has been approved for the treatment of advanced melanoma by FDA and EMA, and, at a dose of 10 mg/kg, for the adjuvant treatment of stage III melanoma by FDA.3,4 The inhibitors of the programmed cell-death protein 1 (PD-1) nivolumab and/or pembrolizumab have been approved by FDA and/or EMA, or have received a positive CHMP opinion for the treatment of advanced melanoma, advanced non-small cell lung cancer (NSCLC), and metastatic renal cell carcinoma.3,4 The anti-PDL1 inhibitor atezolizumab is under accelerated FDA review for advanced urothelial carcinoma which had disease progression after platinum-based chemotherapy, and prolongs survival in second line NSCLC patients.5,6 Nivolumab prolongs survival as second line treatment in Squamous Cell Carcinoma of the Head and Neck (SCCHN).7 Over 450 trials with atezolizumab, pembrolizumab, or nivolumab are registered at clinicaltrials.gov.8 More than 40 randomized phase III trial are planned or recruiting patients with NSCLC, advanced small cell lung cancer, multiple myeloma, Hodgkin lymphoma, SCCHN, gastric or gastroesophageal junction adenocarcinoma, esophageal carcinoma, hepatocellular carcinoma, urothelial cancer, triple negative breast cancer, colorectal cancer, glioblastoma, and renal cell carcinoma. All these phase III trials are planned to be completed by the end of 2020.8
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