The European Medicines Agency (EMA) has recommended that the marketing authorisation for olaratumab be revoked based on its completed assessment of the phase III ANNOUNCE trial. The EMA concluded that olaratumab combined with doxorubicin does not prolong the lives of patients with advanced or metastatic soft tissue sarcoma compared with doxorubicin alone and recommends that:
The marketing authorisation for olaratumab be revoked
No new patients should receive olaratumab
Doctors should consider other available treatment options for patients already on olaratumab.
Based on the available information, there are no safety concerns with the medicine.
In November 2016, olaratumab received conditional marketing authorisation approval (one of the EU’s early access routes for medicines that target serious, debilitating, life-threatening, or rare disease) for the treatment of advanced soft tissue sarcoma not amenable to curative treatment, in combination with doxorubicin. At the time of approval, data on the effects of the treatment were limited due to the small number of patients included in the main study supporting the application. The marketing authorisation of olaratumab was, therefore, approved on the proviso that additional data from the phase III ANNOUNCE trial confirmed the efficacy and safety of the medicine in patients with advanced or metastatic soft-tissue sarcoma. The study did not meet its primary efficacy objective of prolonging survival (HR: 1.05; median 20.4 vs. 19.7 months for olaratumab plus doxorubicin compared with doxorubicin, respectively). Nor did olaratumab plus doxorubicin prolong progression-free survival (HR: 1.23; median 5.4 vs 6.8 months months for olaratumab plus doxorubicin compared with doxorubicin, respectively).See Management: approach
Sarcoma is a group of rare solid tumours of connective tissue. More than 50 different histological subtypes are known.
Most commonly, it presents as a soft-tissue swelling, which may or may not be painful. Differential diagnoses that should be considered are lymphoma, metastatic carcinoma, and benign lesions such as lipoma and neuroma.
Some sarcomas are associated with specific gene mutations, in particular chromosomal translocations.
Diagnosis is made by biopsy, which should have a sufficient amount of tissue for accurate pathological diagnosis.
Pathology should be reviewed by an expert pathologist who has experience in sarcoma histology. Diagnostic laboratory methods may include immunohistochemistry, cytogenetics, and molecular genetic testing.
Treatment is based on stage and histological subtype, with only some subtypes being chemotherapy-sensitive.
Sarcoma is a group of rare solid tumours originating in mesenchymal (connective tissue) cells and accounting for 1% of all adult malignancies. They can be divided into 2 broad categories: sarcoma of soft tissues (including fat, muscle, nerve and nerve sheath, blood vessels, and other connective tissue) and sarcoma of bone. More than 50 different histological subtypes of sarcoma of soft tissues are known.
Assistant Professor of Clinical Medicine
USC Norris Comprehensive Cancer Center
JSH declares that he has no competing interests.
USC Norris Comprehensive Cancer Center
SS declares that she has no competing interests.
Sarcoma Oncology Center
SPC declares that he has no competing interests.
Dr Swati Sikaria, Dr James S. Hu, and Dr Sant P. Chawla would like to gratefully acknowledge Dr Jonathan C. Trent, Dr Saira Hassan, and Dr David Thomas, previous contributors to this monograph. JCT and SH each declare that they have no competing interests. DT has received research support from Pfizer, Amgen, and Novartis.
Department of Surgical Sciences
Professor and Chairman
University of Udine
AF declares that he has no competing interests.
Professor of Musculoskeletal Pathology
Institute of Orthopaedics and Musculoskeletal Science
University College London
AF declares that she has no competing interests.
Memorial Sloan-Kettering Cancer Center
RM declares that he has no competing interests.
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