Carfilzomib combinations in ENDEAVOR and FORTE

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Published: 23 Jun 2017
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Prof Katja Weisel - University of Tübingen, Tübingen, Germany

Dr Weisel speaks with ecancer at EHA 2017 about the ENDEAVOR trial, a head to head comparison of bortezomib or carfilzomib with dexamethasone in relapsed/refractory multiple myeloma.

Based on results from this trial, NICE gave its recommendation of carfilzomib and dexamethasone in this indication, given its extension of overall survival.

In the FORTE trial, also being reported at the conference, carfilzomib and dexamethasone was combined further with cyclophosphamide, which Dr Weisel considers against novel monotherapies.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

Here also at the EHA the ENDEAVOR trial is presented. The ENDEAVOR trial is one of the very rare trials performing a head-to-head comparison. The ENDEAVOR trial compared bortezomib dexamethasone versus carfilzomib dexamethasone in patients with relapsed multiple myeloma after having had one, two, three prior treatment lines. The primary analysis showed that the carfilzomib treatment showed a highly significant benefit in progression free survival compared to the bortezomib treatment so that the proteasome inhibitor of the second generation was significantly more effective regarding the primary endpoint.

More importantly now with a longer follow-up here the data presented that carfilzomib dexamethasone has also an overall survival benefit when compared to bortezomib dexamethasone so that we now see that relapsed and refractory multiple myeloma patients have an overall survival benefit when they are treated with carfilzomib/Dex versus bortezomib/Dex. So that this proteasome inhibitor of the new generation in this indication is better regarding both PFS and OS.

Then it’s carfilzomib, dexamethasone and cyclophosphamide in the FORTE trial, is that right?

There are also data with this combination. This is a very interesting combination also for patients for first line treatment and we have to see how it stands in comparison to the upcoming standard of combining proteasome inhibitor, IMiD and dexamethasone and even probably monoclonal antibodies in first line treatment. But it’s a very interesting alternative where we see encouraging data.

Is there anything else you’d like to add? Any final summary?

The proteasome inhibitors per se are still standard of care in many situations and we see that when we have more and more the use of IMiDs in front line and we generate more and more IMiD refractory patients probably in front line, in the relapsed setting we need pure proteasome inhibitory treatment or base treatments for our patients developing an IMiD refractoriness. Carfilzomib in combination with dexamethasone is here a very, very important treatment. The daratumumab bortezomib dexamethasone combination is also a treatment with very good results. But the conclusion of both trials, CASTOR and ENDEAVOR, is that bortezomib dexamethasone alone is not any more a standard in relapsed multiple myeloma.