Drs. Neal Bhatia and Ted Rosen
Part 2 of an 8-part series on the large number of new topical and systemic medications that have become available or moved closer to approval in the last 12 months.
You may never prescribe these products, but you should still know about them.
The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation this pathway has been shown in a variety of human cancers, including, basal cell carcinoma (BCC). Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and other transcription factors. Sonidegib (Odomzo®) is an oral, selective SMO inhibitor approved by the FDA in July of 2015 for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy. Approval of Odomzo was based on results from the BOLT trial which indicated an objective response rate of 58% for patients treated with 200 mg Odomzo. The most serious risks with Odomzo are embryo-fetal toxicity and musculoskeletal adverse reactions including rhabdomyolysis.
Soft tissue sarcomas (STSs) are a group of rare tumors that are often diagnosed after after metastases have developed. Doxorubicin either alone or in combination with ifosfamide has been used as first-line chemotherapy for advanced disease and high-dose ifosfamide, gemcitabine plus docetaxel, and dacarbazine have been employed for second-line treatment, albeit with little supporting evidence. Trabectedin (Yondelis®) is a synthetic, marine-derived alkylating agent derived from the Caribbean tunicate, Ecteinascidia turbinate and it was approved by the FDA for treatment of unresectable or metastatic liposarcoma and leiomyosarcoma in October of 2015. The efficacy of Yondelis for STSs was demonstrated by results from the TRUSTS trial and the most frequently reported grade 3/4 adverse events in this study were neutropenia and elevated hepatic transferases. Steroid pretreatment is effective for reducing hepatotoxicity with Yondelis, and steroids are now given routinely before administration of the drug. Further studies are ongoing to evaluate the efficacy and safety of combination therapy of Yondelis with other agents.