Last reviewed:September 2019
Last updated:February  2019
09 May 2019

EMA recommends withdrawal of olaratumab for the treatment of soft- tissue sarcoma

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.[39] 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

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • mass
  • upper/lower gastrointestinal bleed
  • rash
  • purplish macular-papular lesions
  • dysfunctional uterine bleeding
  • increased abdominal girth
  • hx of HIV infection
  • features of acute abdomen
  • neuropathic pain

Other diagnostic factors

  • weight loss
  • fatigue
  • anorexia
  • abdominal bloating, discomfort, pain
  • unilateral extremity swelling

Risk factors

  • genetically inherited syndromes
  • radiation
  • human herpesvirus-8 (HHV-8) infection
  • congenital disorders
  • lymphoedema
  • hx of exposure to chemical carcinogens

Diagnostic investigations

1st investigations to order

  • CT scan of primary tumour
  • MRI of primary tumour
  • CT scan chest
  • HIV test
Full details

Investigations to consider

  • ultrasound of primary tumour
  • chest x-ray
  • positive emission tomography scan
  • endoscopy
  • biopsy for histology
  • FBC
  • urea
  • creatinine
  • LFTs
  • echocardiogram or multi-gated acquisition (MUGA) scan
  • genetic testing
Full details

Treatment algorithm

Contributors

Assistant Professor of Clinical Medicine

USC Norris Comprehensive Cancer Center

Los Angeles

CA

Disclosures

JSH declares that he has no competing interests.

Fellow

USC Norris Comprehensive Cancer Center

Los Angeles

CA

Disclosures

SS declares that she has no competing interests.

Director

Sarcoma Oncology Center

Santa Monica

CA

Disclosures

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.

Peer reviewersVIEW ALL

Director

Department of Surgical Sciences

Professor and Chairman

ENT Clinic

University of Udine

Udine

Italy

Disclosures

AF declares that he has no competing interests.

Professor of Musculoskeletal Pathology

Institute of Orthopaedics and Musculoskeletal Science

University College London

Stanmore

UK

Disclosures

AF declares that she has no competing interests.

Medical Oncologist

Memorial Sloan-Kettering Cancer Center

New York

NY

Disclosures

RM declares that he has no competing interests.

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