OncoBone recently published a new review article in the Journal ‘Frontiers in Immunology’. The publication ‘Insights into immuno-oncology drug development landscape with focus on bone metastasis’ was a collaboration with Bioseeker Group and the publication was made possible by using their 1stOncology database for searching novel immunotherapies with effects on bone metastases. The publication summarizes key data of 24 emerging immunotherapies currently evaluated in clinical trials with potential efficacy on bone metastasis.
Bone metastases are an unmet medical need
Metastases are the main cause of cancer-related deaths and bone is among the major sites of metastasis in many cancers such as breast, prostate, lung, renal, colon and bladder cancer and melanoma. Breast and prostate cancer patients are most affected by bone metastases and about 70-90% of advanced stage patients develop bone metastases at end-stage disease. Notably, when bone metastases are observed, the 5-year survival rate drops to 5% as there are no effective treatments available. Bone metastases are incurable and induce severe skeletal-related effects such as pathological fractures, spinal cord compression, bone pain and decreased quality of life.
Immunotherapy development for bone metastasis
Despite the success of immunotherapies in oncology, no immunotherapies are approved for bone metastasis and no clear benefit has been observed with approved immunotherapies in treatment of bone metastatic disease.Bone is a highly immunosuppressed microenvironment, which may explain why immunotherapies have not produced promising effects on bone metastatic patients. We have recently established a novel osteoimmuno-oncology (OIO) concept that refers to interactions between cancer, bone and immune cells. It is essential to understand these interactions in order to develop effective and safe therapies for cancer patients with bone metastases. The OIO concept is supported by years of research on the role of interactions between cancer, bone and immune cells, and also by observations in patients treated with different immunotherapies who developed skeletal-related adverse events (SRAEs) such as resorptive bone lesions, spinal cord compression and even fractures. Therefore, development of novel therapies with confirmed efficacy on bone metastasis and without causing SRAEs should be prioritized especially for bone metastatic patients who already have compromised bone health.
Data search in 1stOncology
The review summarizes current immuno-oncology drug development landscape for bone metastatic breast and prostate cancer. Using 1stOncology, a comprehensive oncology-focused drug development database that contains detailed scientific, clinical and commercial drug information on almost 20,000 oncology drugs and 1,877 targets and covers more than 21,000 interventional clinical trials in 391 indications, we identified drugs with preclinical or clinical data available in the context of bone metastasis.
As a conclusion of the database search we identified and evaluated 24 therapies in development that are described in more detail in the review.
Summary of the main findings
- Bone metastasis drug development is variable, including different treatment modalities, treatment routines, inclusion and exclusion criteria for patients and follow-up of tumor response
- The treatments that we evaluated to be most promising are related to targets with close connection to tumors growing in bone metastatic microenvironment, and their clinical evaluation followed outcomes in bone metastatic patients
- We also identified cases where a therapy showed promising efficacy on breast cancer bone metastasis but no effects in prostate cancer bone metastasis, demonstrating the difference between tumor types
- Only a few of the identified therapies were tested, or had published data available, in appropriate preclinical bone metastasis models to support the decision to move forward to clinical trials including patients with bone metastases
- Guidance on how to study and evaluate effects of therapies on bone metastases in clinical trials should be established to provide more concrete guidance on how to evaluate anti-cancer effects on bone metastasis by utilizing imaging and biomarker strategies
- Publication strategies of drug development companies heavily depend on intellectual property rights. Therefore, studies are often published during later development phases and different data sources and databases are important tools to follow real-time drug development
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