Immunotherapies are one of the most effective strategies available for the treatment of cancer. However, the combinations of different immunotherapies and combinations of immunotherapies with the conventional therapeutic methods have now taken over cancer treatment by generating a more robust anti-cancer response as compared to monotherapies. Some drug combinations have been given approval by the FDA and EMA, but a huge number of these are still in clinical trials. Based on the bulky number of these clinical trials, it is expected that in the coming years, more drug combinations will be given approval by the drug regulatory agencies and form a large chunk of all cancer treatment methods According to Neeraj Chawla, Research Head at Kuick Research, currently more than 450 antibodies combinations are under clinical investigation and around 65 combinations are commercially available in market with market opportunity of USD 60 Billion.
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Combination therapies are comparatively better than singular therapies because they attack cancer tumors by inhibiting many pathways at once, preventing the cancer cells from becoming tolerant or resistant to the treatment. There are commercially available drugs in the market today; therefore, there are an endless number of possibilities available for making potential combinations for cancer treatment. One of the most recent combinations to be given approval was Lynparza in combination with abiraterone and prednisolone and prednisone by the EMA. The combinations were demonstrated to increase progression free survival in in male adults with metastatic castration-resistant prostate cancer (mCRPC). The combination of the drugs has been suggested for specifically those patients who have shown no response to chemotherapy, making the combination therapy one of the final treatment approaches for these patients.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended a combination of Imfinzi (durvalumab) and Imjudo (tremelimumab), together forming the STRIDE regimen, for the treatment of advanced liver and lung cancers. This was backed with the results of the phase 3 HIMALAYA trial conducted by AstraZeneca wherein the overall survival rate of the patients was increase by huge folds when compared to monotherapy with the two drugs. In addition, the combination was also granted priority review by the US FDA last year for the treatment of patients with unresectable hepatocellular carcinoma (HCC) based on the same phase 3 HIMALAYA trial.
Combination therapies have been gaining a lot attention recently, with many drug candidates undergoing clinical trials to investigate their combinations with other drugs parallel to their monotherapies. For examples, ADG126 developed by Adagene, is undergoing a global phase 1 clinical trial for treatment of advanced/metastatic solid tumors. However, the company also announced clinical trial collaboration with Roche last month to evaluate the triple combination of ADG126 with Roche’s Tecentriq (atezolizumab) and Avastin (bevacizumab).. Triple combination of drugs for cancer therapy has been suggested as the next step to dual drug combinations, and has shown improved results in trials and offer effective long term results. Though using more drugs in a cocktail increases the chances of developing adverse effects, they can be managed through other routes, thus maximizing the benefits of the treatment.
Other therapy techniques, such as CAR-T treatments, have also been used as agents in combination therapies in addition to drugs. The development of CAR-T cell therapy, which has shown promise in the treatment of hematological malignancies and is currently being used to treat solid tumors, has transformed the way that cancer is treated. The idea of employing CAR-T treatments as a combining agent has received support from numerous clinical trials. By altering the tumor microenvironment, improving the CAR structure, connecting the CAR-T cells to the tumor cells, potentially targeting multiple antigens, avoiding tumor-immune escape mechanisms, and reducing the toxic effects of CAR-T cell therapy, these combinatorial treatment approaches increase the safety and efficacy of CAR-T cells.
Combination treatment with drugs and therapies is not an emerging idea; but as researchers learned about the mechanisms of action of different treatment modalities, the combinations of these started getting more attention. In the last few decades, a number of cocktails of drugs have been approved by the FDA and EMA and the combinations of drugs with chemotherapy and radiation have also improved the quality of the treatment and the patient’s life after treatment. As more drugs enter the pipeline, more combinations of drugs and therapies are expected to enter clinical trials and get the green light from regulatory bodies.
