A Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Cancer

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dc.contributor.authorZhang, Jingsongen
dc.contributor.authorGallaher, Jillen
dc.contributor.authorCunningham, Jessica J.en
dc.contributor.authorChoi, Jung W.en
dc.contributor.authorIonescu, Filipen
dc.contributor.authorChatwal, Monica S.en
dc.contributor.authorJain, Rohiten
dc.contributor.authorKim, Youngchulen
dc.contributor.authorWang, Liangen
dc.contributor.authorBrown, Joel S.en
dc.contributor.authorAnderson, Alexander R.en
dc.contributor.authorGatenby, Robert A.en
dc.date.accessioned2023-04-26T17:46:07Zen
dc.date.available2023-04-26T17:46:07Zen
dc.date.issued2022-11en
dc.description.abstractSimple Summary Despite early utilization of new hormonal agents (NHA, i.e., abiraterone, enzalutamide and apalutamide) for combined androgen deprivation therapy (ADT) for metastatic prostate cancer, increasingly more men are dying from this disease. While continued development of new drugs is needed, we propose that improved survival of metastatic prostate cancer can be obtained through evolutionarily informed treatment strategies that adjust patient-specific-dosing to their current and past Prostate Specific Antigen (PSA) levels. Compared to the conventional treat-until-progression paradigm, our previous study in metastatic castration resistant prostate cancer (NCT02415621) showed that an on-and-off abiraterone therapy adapted to an individual's PSA response dynamics provided better cancer control with less drug usage. Here, we report the feasibility of applying this strategy to newly diagnosed metastatic prostate cancer. On-and-off ADTs with luteinizing hormone releasing hormone (LHRH) analog, an NHA, or in combination were based on individual's testosterone and PSA levels. The current study represents the foundation for future efforts to validate our adaptive therapy in randomized controlled studies for metastatic prostate cancer. Background: We hypothesize that cancer survival can be improved through adapting treatment strategies to cancer evolutionary dynamics and conducted a phase 1b study in metastatic castration sensitive prostate cancer (mCSPC). Methods: Men with asymptomatic mCSPC were enrolled and proceeded with a treatment break after achieving > 75% PSA decline with LHRH analog plus an NHA. ADT was restarted at the time of PSA or radiographic progression and held again after achieving >50% PSA decline. This on-off cycling of ADT continued until on treatment imaging progression. Results: At data cut off in August 2022, only 2 of the 16 evaluable patients were off study due to imaging progression at 28 months from first dose of LHRH analog for mCSPC. Two additional patients showed PSA progression at 12.4 and 20.5 months and remain on trial. Since none of the 16 patients developed imaging progression at 12 months, the study succeeded in its primary objective of feasibility. The secondary endpoints of median time to PSA progression and median time to radiographic progression have not been reached at a median follow up of 26 months. Conclusions: It is feasible to use an individual's PSA response and testosterone levels to guide intermittent ADT in mCSPC.en
dc.description.notesThe funding support from Moffitt Cancer Center, clinical trial innovation award.en
dc.description.sponsorshipMoffitt Cancer Center, clinical trial innovation awarden
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3390/cancers14215225en
dc.identifier.eissn2072-6694en
dc.identifier.issue21en
dc.identifier.other5225en
dc.identifier.pmid36358643en
dc.identifier.urihttp://hdl.handle.net/10919/114803en
dc.identifier.volume14en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectadaptive therapyen
dc.subjectprostate canceren
dc.subjectandrogen deprivation therapyen
dc.subjectabirateroneen
dc.subjectenzalutamideen
dc.subjectapalutamideen
dc.titleA Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Canceren
dc.title.serialCancersen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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