eUpdate – Soft tissue and Visceral Sarcomas: ESMO–EURACAN Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up

Published: 22 March 2019. Authors: ESMO Guidelines Committee

Note: Other eUpdates may have been published for these guidelines. All currently valid eUpdates can be accessed from the page displaying the full guidelines on this topic

Clinical Practice Guidelines

This update refers to Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Casali PG, Abecassis N, Bauer S et al. Ann Oncol 2018 ;29 (Suppl 4): iv51-iv67.

Section

Management of advanced/metastatic disease

Text update

Recently, a relatively small phase II study tested the combination of doxorubicin with an antibody directed against platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, and showed a statistically significant higher OS in comparison with doxorubicin alone, though with a lower and non-statistically significant benefit in PFS and response rate [28]. Olaratumab is available in some countries, and the results of a subsequent phase III trial (whose accrual is already completed) are awaited so that the drug can be administered more widely in Europe [II, Cb, see note b in Table 2; ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.1 score: 4]. The mechanisms for the added value of the combination of doxorubicin with a PDGFRA inhibitor are not fully understood.

Is replaced with:

Recently, a relatively small phase II study tested the combination of doxorubicin with an antibody directed against platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, and showed a statistically significant higher OS in comparison with doxorubicin alone, though with a lower and non-statistically significant benefit in PFS and response rate [28]. In view of the recent communication of the  failure of the ANNOUNCE (NCT02451943) phase III trial to confirm a survival advantage of olaratumab in first-line treatment  of advanced soft tissue sarcoma (Press Release on Jan 18, 2019 – referenced below), ESMO and EURACAN have to remove this agent from the list of  options in the Clinical Practice Guidelines of advanced soft tissue and visceral sarcomas, until further information or additional results from clinical research are available. The ESMO-MCBS score calculated on the basis of the initial randomised phase II study must also be modified: it is not possible to recalculate the new ESMO-MCBS of olaratumab in the absence of the formal publication of the study report.

For patients already on olaratumab treatment resulting in patient benefit, the attending physician may opt to continue or not.

Section

Table 2. Summary of Recommendations, Management of advanced/metastatic disease

Text update

• The combination of doxorubicin with an anti-PDGFRA agent, olaratumab, is option [II, Cb; ESMO-MCBS v1.1 score: 4]

Is removed from the list of options.

bThe experts noted that no GoR described the accurate situation in terms of scientific evidence. Indeed, GoR B is ‘Strong or moderate evidence for efficacy but with a limited clinical benefit, generally recommended’, while GoR C is ‘Insufficient evidence for efficacy or benefit does not outweigh the risk or the disadvantages (adverse events, costs, . . .), optional’. In the present question, the experts observed that ‘Moderate evidence for efficacy but with a major clinical benefit’ would have been a better description of the scientific evidence at this stage, while waiting for the results of the completed phase III trial.

Is removed from the footnotes.

Section

Table 3. ESMO-MCBS table for olaratumab and eribulin in soft tissue and visceral sarcomasa

Text update

New title Table 3. ESMO-MCBS table for eribulin in soft tissue and visceral sarcomasa

The first row of the table ‘Olaratumab with doxorubicin’

Is removed from the table.

Background text describing the reasons for update and data

In view of the recent  communication of the  failure of the ANNOUNCE (NCT02451943)  phase III trial to confirm  a survival advantage of olaratumab in first-line treatment  of advanced soft tissue  sarcoma (Press Release on Jan 18, 2019), the ESMO and EURACAN have to remove  this agent from the list of  options in the  Clinical Practice Guidelines of advanced soft tissue and visceral sarcomas, until further information or additional results from clinical  research. The MCBS score calculated on the basis of the initial randomised phase II study must also be modified: it is not possible to recalculate the new MCBS of olaratumab in the absence of the formal publication of the study report.

Recommendation

The ESMO and EURACAN have to remove this agent from the list of options in the Clinical Practice Guidelines of advanced soft tissue and visceral sarcomas.

In the absence of a formal available peer reviewed publication, it is not possible to attribute a definitive level of evidence (LoE) or grade of recommendation (GoR). However, according to the European Medicines Agency (EMA) Press Release [1], it can be proposed that the LoE is 1 and GoR E for the use of olaratumab in combination with doxorubicin in advanced soft tissue sarcoma until further information.

Because this is a major change compared to the previous recommendation, it is important for the Guidelines Committee to share this new recommendation with the scientific and medical community.

References

  1. https://www.ema.europa.eu/documents/press-release/no-new-patients-should-start-treatment-lartruvo-after-study-shows-cancer-medicine-does-not-prolong_en.pdf (20 February 2019, date last accessed)