Asco preview – Jevtana fails to beat docetaxel in prostate cancer
Sanofi is going into Asco braced for the painful disclosure of a failed head-to-head study that it had hoped could revive the fortunes of its tired flagship oncology drug Jevtana. The Firstana phase III trial was designed to show overall survival superiority against docetaxel but has failed to do so, and the data suggest that the two drugs are equally effective.
These results might have been part of the motivation for Sanofi’s recent bid for Medivation, since its need to find another product to rebuild an oncology franchise around must be increasingly pressing. Sanofi’s best hope for reviving the fortunes of Jevtana will now come from the co-operative group-sponsored Peace II study that aims to position the drug as adjuvant to radiotherapy in localised disease, but does not read out until 2018. (For a background on cancer topics emerging at Asco see our free report.)
The finding that Jevtana is the equal of docetaxel will offer little consolation in commercial terms, since docetaxel – which Sanofi itself originated – is now generic. And in scientific terms it is also unsurprising, since the two drugs are chemically related.
Jevtana is approved for second-line post-docetaxel use in metastatic castration-resistant prostate cancer (mCRPC), and there it seems likely to remain. In recent years it has been marginalised by the introduction of other agents such as the androgen receptor blockers Xtandi and Zytiga, and Bayer’s Xofigo.
No Jevtana Stampede
Further complicating the picture is the finding from the academic study Stampede, presented at Asco last year, which established that docetaxel given earlier to men who are still hormone sensitive conferred a 10-month survival advantage. This level of benefit was much greater than that available when docetaxel is used in mCRPC, its traditional setting.
Since then prostate cancer patients have increasingly had docetaxel initiated when they are still hormone sensitive. And, although Firstana showed equivalence in mCRPC, it seems unlikely Jevtana would be used in preference to docetaxel in any other prostate cancer setting.
The Asco abstract shows first-line Jevtana and docetaxel to be equivalent numerically for OS and PFS, with only tumour response superior for the higher of the two doses of Jevtana. As if that were not enough, another phase III study of Jevtana to be presented at Asco has shown non-inferiority for the lower 20mg/m
The increasingly dynamic treatment landscape in prostate cancer could shift markedly if one or more of a number of competitor studies read out positively. Almost all of these studies seek to position their sponsor’s products earlier in the treatment hierarchy and thus in the course of the disease. EP Vantage’s review of the currently ongoing phase III studies is shown in the table below; ordered, as far as possible, by disease stage.
|Phase III studies in prostate cancer|
|Docetaxel + LHRH agonist||Various||750||surgery +/-||neo-adjuvant||NCT00430183|
|Prostatak||Advantagene||711||vs placebo||localised, adjuvant to RT||NCT01436968|
|Jevtana + ADT||Sanofi||1,048||vs placebo||localised, adjuvant to RT||NCT01952223 (Peace 2)|
|Xtandi||Astellas/ Medivation||800||vs ADT||localised, adjuvant to RT||NCT02446444|
|Apalutamide||J&J||1,500||vs bicalutamide||localised, adjuvant to RT||NCT02531516|
|Xtandi||Astellas/ Medivation||1,860||Leuprolide +/-||Non-metastatic HSPC||NCT02319837|
|Zytiga||J&J||1,209||ADT +/-||mHSPC, hormone naive||NCT01715285|
|Zytiga||J&J||916||ADT +/- RT +/-||mHSPC, hormone naive||NCT01957436 (Peace 1)|
|Apalutamide||J&J||1,200||vs placebo||chemo/AR inhibitor-naive, non-metastatic CRPC||NCT01946204 (Spartan)|
|BAY1841788||Bayer||1,500||vs placebo||chemo/AR inhibitor-naive, non-metastatic CRPC||NCT02200614|
|Xtandi||Astellas/ Medivation||1,560||vs placebo||chemo/AR inhibitor-naive, non-metastatic CRPC||NCT02003924|
|Galeterone||Tokai||148||vs Xtandi||chemo/AR inhibitor-naive mCRPC, AR-V7 variant||NCT02438007|
|Jevtana||Sanofi||174||vs docetaxel||chemo-naive mCRPC||NCT02044354|
|Prostvac||Bavarian Nordic/BMS||1,298||+/- GM-CSF vs placebo||chemo-naive mCRPC||NCT01322490|
|Zytiga||J&J||313||vs placebo||chemo-naive mCRPC||NCT01591122|
|Xofigo||Bayer||800||Zytiga +/-||chemo-naive mCRPC||NCT02043678|
|DCCVAC||Sotio||1,170||docetaxel +/-||chemo-naive mCRPC||NCT02111577|
|Xtandi||Astellas/ Medivation||650||docetaxel +/-||post-Xtandi, chemo-naive mCRPC||NCT02288247|
|Apalutamide||J&J||960||Zytiga +/-||chemo-naive, mCRPC||NCT02257736|
|Xofigo||Bayer||560||Xtandi +/-||chemo-naive, mCRPC||NCT02194842|
|Zytiga||J&J||1,224||Xtandi +/-||chemo-naive mCRPC||NCT01949337|
|Masitinib||AB Science||581||docetaxel or gemcitabine +/-||2nd-line mCRPC||2013-000809-23|
As can be seen, the investigator-sponsored Peace I study, which is due to read out this year, has the potential to move Zytiga into the metastatic androgen deprivation therapy (ADT)-naive, hormone-sensitive stage.
J&J itself is conducting a similar study in this setting that reads out in 2018, but its focus seems to be on the follow-up molecule apalutamide. Its Spartan phase III study of this agent reads out this year in chemo/AR inhibitor-naive, non-metastatic CRPC.
When it comes to new study results in prostate cancer with practice-changing potential, the abstracts suggest that this year’s Asco will to be light compared to last year, but there is still much scope for discussion around the position of existing therapies in the treatment landscape.
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