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BLADDR2019 - case 4

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Your case challenge related to data presented at ASCO

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You answered: A
A) Test tumour for FGFR gene alterations - B) Start enfortumab vedotin (within trial) - C) Start chemotherapy with vinflunine or taxane
 

What would Ignacio Duran do? 

This patient has advanced UCa and progressive disease after chemotherapy and immunotherapy.

The three proposed options could be valid. Each option deserves further explanation.

Fibroblast growth factor receptor (FGFR) gene alterations are common in urothelial carcinoma and may be associated with lower responses to immunotherapy. On the other hand, data presented by Siefker-Radtke at ASCO 2018 and updated recently at ASCO 2019 revealed that patients with pre-specified FGFR gene alterations, presented significant responses to erdafitinib with confirmed ORR of 40% (3% complete response, 37% partial response) [Park SH et al. J Clin Oncol 2019;37: abs 4543]. Furthermore, when analysing only patients who progressed on prior immunotherapy, the confirmed ORR raised to 59%. These data led to recent FDA approval of erdafitinib. Therefore my first action would be to test Fabienne’s tumour for an FGFR gene alteration and if present, try to get her treated with this compound (in Europe this would be in a clinical trial).

At the recent ASCO meeting, Dr. Petrylak presented the results of a phase II study with enfortumab vedotin (EV) [Petrylak DP et al. J Clin Oncol 2019;37:abs LBA4505]. This compound is an antibody-drug conjugate. It binds to a protein universally expressed in UCa (NECTIN-4) and then internalises a cytotoxic compound attached to it. The results are very solid and revealed remarkable activity of EV in a cohort of patients who had progressed on immunotherapy. I would try to get Fabienne exposed to EV via a clinical trial with this compound.

There still is a role for chemotherapy in patients like Fabienne [Gómez De Liaño A and Duran I. Ther Adv Urol 2018;10:455-80], but these are exciting times in which alternatives for chemotherapy are becoming available and should be prioritised when available. If Fabienne’s tumour does not harbour FGFR mutations and we do not have access to an EV trial, chemotherapy with vinflunine would be my preferred option with a close follow up. If disease progression would occur on this treatment, data of new compounds such as the Bruton Kinase Inhibitor (ibrutinib) have been presented at ASCO 2019 with promising activity in this context [Castellano D et al. J Clin Oncol 2019;37:abs 4522].

I hope you can join us in Paris for BLADDR 2019 on 25-26th October to further discuss these data.  
 


What would Igancio Duran do?

This patient has advanced UCa and progressive disease after chemotherapy and immunotherapy.

The three proposed options could be valid. Each option deserves further explanation.

Fibroblast growth factor receptor (FGFR) gene alterations are common in urothelial carcinoma and may be associated with lower responses to immunotherapy. On the other hand, data presented by Siefker-Radtke at ASCO 2018 and updated recently at ASCO 2019 revealed that patients with pre-specified FGFR gene alterations, presented significant responses to erdafitinib with confirmed ORR of 40% (3% complete response, 37% partial response) [Park SH et al. J Clin Oncol 2019;37: abs 4543]. Furthermore, when analysing only patients who progressed on prior immunotherapy, the confirmed ORR raised to 59%. These data led to recent FDA approval of erdafitinib. Therefore my first action would be to test Fabienne’s tumour for an FGFR gene alteration and if present, try to get her treated with this compound (in Europe this would be in a clinical trial).

At the recent ASCO meeting, Dr. Petrylak presented the results of a phase II study with enfortumab vedotin (EV) [Petrylak DP et al. J Clin Oncol 2019;37:abs LBA4505]. This compound is an antibody-drug conjugate. It binds to a protein universally expressed in UCa (NECTIN-4) and then internalises a cytotoxic compound attached to it. The results are very solid and revealed remarkable activity of EV in a cohort of patients who had progressed on immunotherapy. I would try to get Fabienne exposed to EV via a clinical trial with this compound.

There still is a role for chemotherapy in patients like Fabienne [Gómez De Liaño A and Duran I. Ther Adv Urol 2018;10:455-80], but these are exciting times in which alternatives for chemotherapy are becoming available and should be prioritised when available. If Fabienne’s tumour does not harbour FGFR mutations and we do not have access to an EV trial, chemotherapy with vinflunine would be my preferred option with a close follow up. If disease progression would occur on this treatment, data of new compounds such as the Bruton Kinase Inhibitor (ibrutinib) have been presented at ASCO 2019 with promising activity in this context [Castellano D et al. J Clin Oncol 2019;37:abs 4522].

I hope you can join us in Paris for BLADDR 2019 on 25-26th October to further discuss these data.    

Do you have an interesting case of your own?

Up to 3 case reports will be selected by the scientific committee for discussion in the official programme of BLADDR 2019.
 

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