Several interesting research developments in immunotherapy for cancer treatment were discussed at this year’s European Multidisciplinary Cancer Congress, (EMCC 2011) formerly known as the joint Congress of the European Cancer Organization and the European Society for Medical Oncology (ECCO-ESMO), in Stockholm.
The past 20 years of laboratory work has improved knowledge on the interaction of malignant tumours and the immune system. This has resulted in better strategies to utilise the immune system in the treatment of cancer. The development of novel immunotherapies has particularly benefited melanoma patients but has the potential to significantly impact the survival of patients with other tumour histotypes such as lung, prostate and kidney cancers.
The treatment of cancer by immunotherapy aims to maintain the immune response against the tumour cells by the manipulation of signalling pathways involved with T cell proliferation.
New data from the first clinical trial in nearly 40 years to demonstrate a significant improvement in overall and prolonged survival in the first-line treatment of advanced melanoma has highlighted the superiority of a new monoclonal antibody that inhibits the cytotoxic T lymphocyte antigen-4 (CTLA-4). The Phase III clinical trial revealed that treatment with ipilimumab (Yervoy) in combination with dacarbazine resulted in a 28% survival benefit compared to dacarbazine alone (median overall survival [OS] 11.2 months vs 9.1 months, hazard ratio [HR] 0.716, p=0.0009).
Treatment with the anti-programmed death (PD)-1 human monoclonal antibody (similar to CTLA-4), which is a negatively regulating molecule expressed on the surface of activated T cells, has resulted in tumour regression without significant toxicities in melanoma patients in a Phase I study. It is viewed as an interesting and promising approach, as with ipilimumab, for use in combination therapy for melanoma.
Combination of immunomodulation agents, both with each other and with traditional chemotherapy, is a key consideration in the management of many advanced cancer patients. However, understanding the mechanisms behind these treatments and how they may complement each other is crucial.
“There is the potential to combine CTLA-4-based immune therapy with targeted therapies such as inhibitors of the mutated BRAF protein – however, such strategies should be approached with caution.”
Melanoma metastasizes frequently to the brain, and brain metastases generally drive the prognosis of melanoma patients. Temozolomide and fotemustine are preferentially used in melanoma patients with brain metastases in the United States and in Europe, respectively, with modest clinical activity. However, the results obtained with either agent are still limited, and efforts are needed to improve the outcome of these patients who are generally excluded from clinical trials. The Phase II Italian study (NIBIT-M1 trial) combining ipilimumab and fotemustine in patients with metastatic melanoma who had brain metastasis has shown promising results. If the effectiveness of this new approach is confirmed, this could offer an exciting evolution on how to manage brain metastases in patients with melanoma.
Targeted novel immunomodulating agents, while still in the early development phase, appear to be making headway in using the body’s immune system to battle various cancers and hold the potential to improve patient outcomes in the near future.