Pitfalls of Current Osteosarcoma Treatment Approaches

Osteosarcomas are rare, yet are the leading cause of deaths due to cancer in the pediatric population. It is a high-grade malignancy of mesenchymal origins. They are the most frequent forms of primary bone tumors and account for approximately 20% of all the bone tumors. With the incident population of less than 2500 in the 7MM (the US, EU5 (the UK, Germany, France, Italy, and Spain), and Japan)in 2017, the rarity of Osteosarcomas makes its management quite bone-breaking. 

Surgery has played an integral role in managing Osteosarcoma. Looking back, 40 years or so, the other name for osteosarcoma meant amputation. That was the time when the only option for solving the problem of progression of Osteosarcoma was limb amputation. Not to miss the psychological trauma and fear of the disease that the patients would have had to go through invading their mental peace and harmony besides the physical pain.  

However, the scientific community, while leveraging technological innovation, has worked tremendously for the betterment of humankind. The Osteosarcoma treatment market landscape has shifted dramatically with the advancements in medical science. With a combination of surgery, radiation therapy, and chemotherapy, the last decades have witnessed the treatment outcomes for Osteosarcoma trekking from limb removal to limb salvage. Although, there are side effects associated with radiation including moist desquamation, edema, ulceration, and skin necrosis as early effects, and alopecia, bone resorption, bone necrosis, tumor induction, bone fibrosis, and pathologic fracture as late effects. However, an increased survival rate of the patients by up to 80% in localized tumors is worth mentioning. (Wittig JC, et.al.). 

The prognosis, however, in the metastatic Osteosarcoma to date remains poor.  Osteosarcomas have a notorious history of penetrating distant organs, and here the cocktail of surgeries, and chemos fail to do magic. Approximately, 50% of the Osteosarcoma patients’ tumor advances to synchronous or metachronous metastatic lung disease. (F. Chen, et. al.). Lung metastases are in particular associated with poor prognosis. The present treatment landscape for metastatic Osteosarcoma offers the same treatment modalities as that of a localized one. Complete surgical resection followed by the same chemotherapeutic agents. 

Osteosarcoma Treatment Market: Multimodal Approaches

At present, the available chemotherapeutic drugs in the Osteosarcoma treatment market involve cisplatin (DDP), doxorubicin, ifosfamide (IFO), and high-dose methotrexate (MTX) with leucovorin calcium rescue (HDMTX). For improved and better outcomes, a combination of two or more drugs is used, since a single-agent treatment is often regarded inadequate as the first-line treatment of Osteosarcoma. Three-to-four cycles of chemotherapy are prescribed pre-operatively and the same is given in adjuvant with surgery. However, if the tumor relapses or recur, the second-line treatment looks quite disappointing and offers nothing special. 

In addition to these, the Osteosarcoma treatment market homes other approved medications. Approved in 2008, Fusilev (Spectrum Pharmaceutical) is recommended to dampen the aftereffects of high-dose methotrexate therapy. However, the drug lost its market exclusivity and had to compete with its generic versions, one of which was launched in the US by Hikma Pharmaceuticals and the other by Sagent Pharmaceuticals. However, Spectrum Pharmaceuticals put the brave face on and to safeguard the legacy of Fusilev, brought in the market another folate analog, Khapzory, but with a touch of sodium in it. Then, in the Osteosarcoma treatment market, after undergoing surgery and in combination with chemotherapies, Takeda advises going for Mepact, an immunomodulator it acquired from IDM Pharm. However, Mepact is available commercially in countries other than the USA due to the concerns of safety the US FDA raised. Even so, the access to Mepact in the US can be gained through In the US the  FDA’s compassionate use and personal importation programs.

Although the Osteosarcoma treatment market has witnessed a lot of improvements in the last many decades, there still remains a lot to cover. There are a lot of unmet needs in the market that continues to widen the treatment gap; Multi-drug-resistance is one of the significant ones. Resistance to chemotherapies is one of the major reasons behind the failure of the current multi-modal treatment approach.  The adjuvant chemotherapies, beyond doubt, have benefitted considerably, however, consolidated chemotherapy or higher doses of prevailing chemotherapies are unable to outwit cancer. Further, the percentage of patients experiencing metastasis and relapse is significantly high. There is a major dearth of effective therapies that have the potential to halt the tumor progression to distant organs, cause minimal toxicities, and provide results in the long-term. 

To bridge these treatment gaps, many pharma, and biotech companies in the Osteosarcoma treatment market including Eisai Limited, Bayer, Exelixis, Nektar Therapeutics, Y-mAbs Therapeutics, GlaxoSmithKline, Novartis, Aadi Bioscience, Eleison Pharmaceuticals,  Aurora biopharma,  BioAtla, Iovance Biotherapeutics,  Bristol-Myers Squibb, Cellestia Biotech, among others are developing novel therapeutic strategies. The companies are exploring a diverse range of therapeutic candidates ranging from IL-2 pathway agonists, multi-kinase inhibitors, monoclonal antibodies, immunotherapies, and several others. 

In a nutshell, there is a call for heightened research and development to gain a clearer biological understanding of the Osteosarcoma and its metastatic potential. As important it is to understand the nature of the tumor, equally important are the efforts to prioritize the development of therapies that target the tumor, shrink their size, and halt their progression. At the same time, there is a requirement for imaging modalities that help in overt the metastases of the tumors. Also, there is stands a major risk of failure of the promising candidate in early-stage trials in the later stages. Thus, it is important to note which therapies in the pipeline are effective enough to prevent metastasis as well as relapse of Osteosarcoma.