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 pressingSanofi’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/m2 dose to the approved 25mg/m2 dose.

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
Agent Company  Enrolment Design  Setting Trial ID
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)
Xtandi Astellas/ Medivation 1,100 ADT+/-  mHSPC NCT02677896
Apalutamide J&J 1,000 ADT +/- mHSPC  NCT02489318
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.

Download our free Asco backgrounder highlighting recent oncology breakthroughs, setbacks and approaching data points.

The author will be reporting live from Asco, which begins on June 3. To contact the writer of this story email Robin Davison at [email protected] or follow @RobinDavison2 on Twitter

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