Potential Value of Rapid Prostate-Specific Antigen Decline in Identifying Primary Resistance to Abiraterone Acetate and Enzalutamide

Caffo, Orazio; Veccia, Antonello; Maines, Francesca; Bonetta, Alberto; Spizzo, Gilbert; Galligioni, Enzo

doi:10.2217/fon.14.24

Cited by 25 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, PSA could be a valid clinical marker to minimize patient exposure to ineffective therapy. Other retrospective studies based on clinical experience such as the Caffo et al one (Caffo et al, 2014 ), aimed at identifying factors predicting primary resistance to new-generation hormonal agents. In this study, the role of these parameters was clearly demonstrated only in the cumulative analysis of patient treated with ENZ while in the AA group was not confirmed.…”

Section: Discussionmentioning

confidence: 99%

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background: Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting.Patients and Methods: We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics.Results: We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6–6.5) and the median OS was 17.1 months (8.8–25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12–0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06–0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days.Conclusion: A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

show abstract

Section: Discussionmentioning

confidence: 99%

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several studies have reported strength of PSA decline and its predictive value for OS, although certain results were controversial [ 9 – 11 ]. Recently, Caffo et al reported the PSA kinetics of AA and enzalutamide responders and demonstrated different trends with regard to PSA kinetics between the drugs in chemotherapy-treated mCRPC patients [ 12 ]. However, patient number was limited, and PSA kinetics of chemotherapy-naïve mCRPC patients was not reported.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the Prostate Cancer Clinical Trial Working Group (PCWG2) advises to ignore early PSA changes to avoid detecting continuing rise of PSA level and increasing in size before it regress [ 8 ]. However, some researchers reported early PSA decline, and its predictive value was possibly different by patient backgrounds and treatment [ 12 , 14 , 15 ]. In addition, the clinical practice in Japan, most of mCRPC patients are primary followed by monthly PSA testing, so, there is a potential of over use of early response as predictive factor for efficacy regardless the PCWG2 criteria.…”

Section: Introductionmentioning

confidence: 99%

Association of early PSA decline and time to PSA progression in abiraterone acetate-treated metastatic castration-resistant prostate cancer; a post-hoc analysis of Japanese phase 2 trials

Nakayama¹,

Kobayashi²,

Takahara³

et al. 2016

BMC Urol

View full text Add to dashboard Cite

BackgroundPrevious studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA.MethodsWe used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP.ResultsPSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan–Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201.ConclusionsOur results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy.Trial registrationThe original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201, registered 20 December 2012 and JNJ-212082-JPN-202, registered 30January 2013.

show abstract

“…In addition, differences in the use of tumour imaging methods are evident; while some patients received bone and/or CT scans multiple times during treatment, others did not receive a CT scan at all, and most decisions were based on the rise of PSA. However, this marker has its limitations [29], although, it has been shown that patients who do not achieve a ≥50% reduction in PSA levels within the first treatment month may have primary resistance to AA or E [30].…”

Section: Discussionmentioning

confidence: 99%

The third line of treatment for metastatic prostate cancer patients: Option or strategy?

Roviello

Petrioli

Laera

et al. 2015

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

Potential Value of Rapid Prostate-Specific Antigen Decline in Identifying Primary Resistance to Abiraterone Acetate and Enzalutamide

Cited by 25 publications

References 26 publications

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

Association of early PSA decline and time to PSA progression in abiraterone acetate-treated metastatic castration-resistant prostate cancer; a post-hoc analysis of Japanese phase 2 trials

The third line of treatment for metastatic prostate cancer patients: Option or strategy?

Contact Info

Product

Resources

About