Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Abstract

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

Treatment-Refractory, Castration-Resistant Prostate Cancer With Liver Metastasis: A Promising Modality of Therapy

“…Despite medication development in the past decade, mCRPC remains deadly with limited therapeutic options [ 5 , 6 ]. The majority of approved anticancer drugs for PC, including enzalutamide, abiraterone/prednisone, docetaxel, and cabazitaxel, do not have a durable impact in the setting of established metastatic liver disease due to acquired therapeutic resistance [ 7 ].…”

Radium‐223 dichloride treatment in metastatic castration‐resistant prostate cancer in Finland: A real‐world evidence multicenter study

“…The quality of life was also reported to be better in the radium‐223 group compared to placebo in ALSYMPCA trial. 15 Interestingly, a recent post hoc analysis of the phase III Proselica trial 28 analyzed pain progression at the initiation of cabazitaxel treatment and found that the pain progression was associated with aggressive disease and shorter survival time compared to the radiological or PSA progression (12.0 vs. 16.8 vs. 18.4 months, respectively, p < 0.001). Pain response could be a potential indicator of the clinical benefit from radium‐223 and a marker of the aggressive course of mCRPC.…”

Outcomes of treatment choices in poor prognosis prostate cancer: not against all odds

“…4,5,[7][8][9][10] Not losing the window of opportunity, especially in patients with poor prognostic features, is of great importance. 11,12 In the study of Annala et al 85 patients were eligible for crossover but only 55 patients (58%) actually received the alternative treatment, mostly due to frailty after the previous treatment. 6 In the CARD study, 22% of patients who progressed in the ARPI arm subsequently received palliative radiotherapy and 36% received no subsequent therapy at all, suggesting >50% of those who progressed may have missed the window of opportunity for receiving the more effective treatment.…”