An update on emerging drugs in osteosarcoma: towards tailored therapies?

ABSTRACT

Introduction: Current treatment of conventional and non-conventional high-grade osteosarcoma (HGOS) is based on the surgical removal of primary tumor and, when possible, of metastases and local reccurrence, together with systemic pre- and post-operative chemotherapy with drugs that have been used since decades.

Areas covered: This review is intended to summarize the new agents and therapeutic strategies that are under clinical evaluation in HGOS, with the aim to increase the cure probability of this highly malignant bone tumor, which has not significantly improved during the last 30–40 years. The list of drugs, compounds and treatment modalities presented and discussed here has been generated by considering only those that are included in presently ongoing and recruiting clinical trials, or which have been completed in the last 2 years with reported results, on the basis of the information obtained from different and continuously updated databases.

Expert opinion: Despite HGOS is a rare tumor, several clinical trials are presently evaluating different treatment strategies, which may hopefully positively impact on the outcome of patients who experience unfavorable prognosis when treated with conventional therapies.

Trial registration: ClinicalTrials.gov identifier: NCT01459484.

Trial registration: ClinicalTrials.gov identifier: NCT01669369.

Trial registration: ClinicalTrials.gov identifier: NCT00134030.

Trial registration: ClinicalTrials.gov identifier: NCT00180908.

Trial registration: ClinicalTrials.gov identifier: NCT00470223.

Trial registration: ClinicalTrials.gov identifier: NCT01532687.

Trial registration: ClinicalTrials.gov identifier: NCT02357810.

Trial registration: ClinicalTrials.gov identifier: NCT03163381.

Trial registration: ClinicalTrials.gov identifier: NCT02432274.

Trial registration: ClinicalTrials.gov identifier: NCT02048371.

Trial registration: ClinicalTrials.gov identifier: NCT02389244.

Trial registration: ClinicalTrials.gov identifier: NCT02243605.

Trial registration: ClinicalTrials.gov identifier: NCT02867592.

Trial registration: ClinicalTrials.gov identifier: NCT03210714.

Trial registration: ClinicalTrials.gov identifier: NCT03526250.

Trial registration: ClinicalTrials.gov identifier: NCT03213678.

Trial registration: ClinicalTrials.gov identifier: NCT03718091.

Trial registration: ClinicalTrials.gov identifier: NCT03233204.

Trial registration: ClinicalTrials.gov identifier: NCT03698994.

Trial registration: ClinicalTrials.gov identifier: NCT03220035.

Trial registration: ClinicalTrials.gov identifier: NCT03220035.

Trial registration: ClinicalTrials.gov identifier: NCT02689336.

Trial registration: ClinicalTrials.gov identifier: NCT03678883.

Trial registration: ClinicalTrials.gov identifier: NCT01962103.

Trial registration: ClinicalTrials.gov identifier: NCT02945800.

Trial registration: ClinicalTrials.gov identifier: NCT01669369.

Trial registration: ClinicalTrials.gov identifier: NCT03598595.

Trial registration: ClinicalTrials.gov identifier: NCT02644460.

Trial registration: ClinicalTrials.gov identifier: NCT02517918.

Trial registration: ClinicalTrials.gov identifier: NCT03002805.

Trial registration: ClinicalTrials.gov identifier: NCT02013336.

Trial registration: ClinicalTrials.gov identifier: NCT02536183.

Trial registration: ClinicalTrials.gov identifier: NCT02557854.

Trial registration: ClinicalTrials.gov identifier: NCT02390843.

Trial registration: ClinicalTrials.gov identifier: NCT03643133.

Trial registration: ClinicalTrials.gov identifier: NCT03006848.

Trial registration: ClinicalTrials.gov identifier: NCT03676985.

Trial registration: ClinicalTrials.gov identifier: NCT03277924.

Trial registration: ClinicalTrials.gov identifier: NCT03190174.

Trial registration: ClinicalTrials.gov identifier: NCT02304458.

Trial registration: ClinicalTrials.gov identifier: NCT02406781.

Trial registration: ClinicalTrials.gov identifier: NCT02502786.

Trial registration: ClinicalTrials.gov identifier: NCT03860207.

Trial registration: ClinicalTrials.gov identifier: NCT03320330.

Trial registration: ClinicalTrials.gov identifier: NCT03610490.

Trial registration: ClinicalTrials.gov identifier: NCT02100891.

Trial registration: ClinicalTrials.gov identifier: NCT02508038.

Trial registration: ClinicalTrials.gov identifier: NCT03356782.

Trial registration: ClinicalTrials.gov identifier: NCT01953900.

Trial registration: ClinicalTrials.gov identifier: NCT03618381.

Trial registration: ClinicalTrials.gov identifier: NCT03462316.

Trial registration: ClinicalTrials.gov identifier: NCT02487979.

KEYWORDS:

• Osteosarcoma
• chemotherapy
• drug resistance
• pharmacogenomics
• biomarkers
• targeted drugs
• tailored therapy

Acknowledgements

The authors’ studies and findings cited in this manuscript were supported by grants from the Foundation AIRC for Cancer Research (funding from AIRC under IG 2018 - ID.21487 project - P.I. Serra Massimo) and Italian Ministery of Health (Project RF-2016-02361373). SL has been supported by a fellowship of the Associazione Onlus “Il Pensatore - Matteo Amitrano”.

Article highlights

• High-grade osteosarcoma (HGOS) is a highly malignant tumor arising in the bone that has to be considered as an orphan disease due to its rarity.

• HGOS overall survival and cure probabilities have not significantly improved during the last 30–40 years and, in particular, the prognosis is still poor for metastatic, refractory or relapsed patients.

• International cooperation is essential to perform clinical trials, which can recruit sufficient numbers of HGOS patients and provide reliable information on the clinical efficacy of each treatment strategy.

• During the last 10–15 years, the provided new insights into HGOS biology and on the interactions between tumor cells and microenvironment have identified potentially druggable targets and pathways, several of which are presently under clinical evaluation.

• Currently active clinical studies are mostly phase I/II trials, mainly recruiting metastatic, refractory and/or relapsed HGOS patients, which may hopefully indicate new agents and therapies to be further tested in phase III studies.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors were supported by grants from the Foundation AIRC for Cancer Research [funding from AIRC under IG 2018 - ID. 21487 project – P.I. Serra Massimo]; Italian Ministry of Health Project [RF-2016-02361373]. SL has been supported by a fellowship of the Associazione Onlus ‘Il Pensatore - Matteo Amitrano’.