Soft-tissue sarcomas (STS) are an uncommon and diverse group of malignancies originating from mesenchymal precursors that are responsible for almost 20% of malignancies in pediatric and 1% of malignancies in adult patients.1 The multiple subtypes of STS make it difficult to diagnose and treat. The National Cancer Institute estimated a diagnosis of 12,310 new cases of STS in the US in 2016 and almost 5,000 deaths due to the disease.2
Until now, doxorubicin either alone or in combination has been the mainstay of therapy for STS. However, the survival of patients treated with this therapy for metastatic disease is only 12–16 months, while the 2-year survival rate is approximately 30%. Few available novel treatments combinations have demonstrated an ability to improve these outcomes. Soft tissue sarcomas therefore represent an unmet medical need.3
Tumor cell proliferation and migration in STS have been attributed to abnormal platelet-derived growth factor receptor (PDGFR) activity. Olaratumab, a recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody was designed to bind to and block PDGFRα, one of the two PDGFR isoforms, with high specificity.4
The U.S. Food and Drug Administration, granted expedited approval to olaratumab (LARTRUVOTM, Eli Lilly and Company) on October 19, 2016 for use in combination with doxorubicin for the treatment of patients with STS with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.5 It also received Fast Track, Orphan Drug, and Breakthrough Therapy designations from the FDA for this indication.6
The expedited approval was based on results of a randomized phase 2 trial comprising 133 patients with metastatic STS.2 Patients received either the combination of olaratumab with doxorubicin or doxorubicin alone. Parameters such as overall survival (OS) i.e., the length of time patients lived after treatment and progression free survival (PFS), i.e., the length of time tumors did not grow after treatment were measured in this trial. Patients receiving the combination of olaratumab and doxorubicin demonstrated a statistically significant improvement OS (median survival of 26.5 months) compared to those receiving doxorubicin alone (median survival of 14.7 months).2 Patients in the combination arm also showed a median PFS of 8.2 months compared to 4.4 months in the monotherapy arm. The objective response rate based on independent review was 18.2% for patients in the combination arm while it was 7.5% in the doxorubicin only arm.2
The most common side effects associated with olaratumab treatment were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy and headache.2
LARTRUVO, in combination with doxorubicin, is the first FDA-approved front-line therapy for STS in four decades.6 The sponsor, Eli Lilly and Company is conducting a larger phase 3 study—ANNOUNCE, to additionally explore the efficacy of olaratumab across the multiple subtypes of STS.2,6
Credits: Dr. Neha Mahadeshwar on behalf of Borderless Access
Copyright © 2016 BorderlessAccess
- Baheti AD, O’Malley RB, Kim S, et al. Soft-tissue sarcomas: an update for radiologists based on the revised 2013 World Health Organization classification. Am J Roentgenol. 2016;206(5):924-932.
- FDA grants accelerated approval to new treatment for advanced soft tissue sarcoma.
- Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388(10043):488-497.
- Poh A. Olaratumab approved for soft-tissue sarcoma. Cancer Discov. 2016;6(12):1297. Epub 2016 Nov 8.
- Lartruvo Prescribing Information.
- FDA Approves Lilly’s LARTRUVO™ (olaratumab) in Combination with Doxorubicin for Soft Tissue Sarcoma