Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer

The Unanticipated Real-World Clinical Experience

Darren M. C. Poon; Kuen Chan; S. H. Lee; T. W. Chan; Henry Sze; Eric K. C. Lee; Daisy Lam; Michelle F. T. Chan

Disclosures

BMC Urol. 2016;16(12) 

In This Article

Results

Characteristics of Patients

Hundred and ten patients were reviewed, of whom 58 were chemo-naïve and 52 were post-chemo. Table 1 summarizes the characteristics of the patient cohort. The median follow-up duration was 7.5 (range, 1.0–24.6) and 11.43 (range, 1.2–30.2) months for chemo-naïve and post-chemo group respectively. Visceral diseases (non-nodal soft tissue metastases) were present in 4 (6.9 %) chemo-naïve and 8 (15.4 %) post-chemo patients. About 30 % of patients were symptomatic prior the initiation of AA.

Clinical Efficacy

PSA Response. The proportion of patients with PSA response (in about half of patients), PSA flare (about 30 % of patients), and eventual response after PSA flare (about two-thirds of patients with flare) were similar between the chemo-naïve and post-chemo groups (Table 2). All of the PSA response was present within the first 3 months of AA.

Duration of AA Treatment and Post-AA Treatment. The median duration of AA treatment was 6.8 (range, 0.6–21.5) and 7.1 (0.5–25.0) months for chemo-naïve and post-chemo group respectively, with 27 chemo-naïve, and 13 post-chemo patients still under treatment at the time of last follow-up. Disease progression was the major reason of treatment discontinuation (Table 2). Continuation of AA treatment beyond disease progression and post-AA treatments were observed in 13/18 and 7/11 chemo-naïve/post-chemo group respectively.

Overall Survival and Progression-free Survival. The median OS was 18.1 (95 % confidence interval (CI): 9.9–25) and 15.5 (95 % CI: 13.8–23.6) months for chemo-naïve and post-chemo group respectively (Fig. 1) whereas their respective median PFS was 6.7 (95 % CI: 4.5–14.7) and 6.4 (95 % CI: 5.4–8.3) months (Fig. 2). Chemo-naïve patients with visceral disease had significantly inferior OS and PFS than those without (OS, 2.8 vs 18.0 months, p = 0.0007, HR: 6.907, 95 % CI: 1.81–25.36; PFS, 2.8 vs 6.8 months, p = 0.0088, HR: 1.79, 95 % CI: 0.73–4.42). In contrast, the differences in OS and PFS were not significant between patients with or without visceral disease in the post-chemo group (Fig. 3).

Figure 1.

The overall survival for mCRPC patients with (post-chemo) or without prior chemotherapy (chemo-naïve) treated with AA

Figure 2.

The progression-free survival for mCRPC patients with (post-chemo) or without prior chemotherapy (chemo-naïve) treated with AA

Figure 3.

The overall survival for a chemo-naïve and b post-chemo mCRPC patients with or without visceral disease, and the progression-free survival for c chemo-naïve and d post-chemo mCRPC patients with or without visceral disease

Pain Control. Improvement in pain control was observed in more than half of the patients (Table 2).

Adverse Events

Table 3 shows the treatment-related toxicities in patients treated with AA. In chemo-naïve group, hypokalemia (3.4 %), hypertension (6.9 %) and peripheral edema (5.2 %) were the commonest grade 3 complications, whereas hypertension (5.8 %), hypokalemia (3.8 %) and elevation of liver enzymes (1.9 %) were the commonest grade 3 toxicities in post-chemo group. There was no grade 4 toxicity or treatment-related death among them.

Univariate and Multivariate Analysis

Chemo-naïve Group. In univariate analysis, 6 variables, including the presence of visceral disease (HR 6.907, 95 % CI 1.881–25.357, p = 0.0007), were significantly determinants of the OS (Table 4). In multivariate analysis, presence of visceral disease (HR 4.8, 95 % CI 1.026–22.465, p = 0.0015), presence of PSA response (HR 0.104, 95 % CI 0.025–0.387, p = 0.0001), short (<10 months) response to prior ADT (HR 2.656, 95 % CI 1.061–6.648, p = 0.0336), ECOG 2 or above (HR 4.907, 95 % CI 1.648–14.612, p = 0.0001), and low hemoglobin level (HR 2.696, 95 % CI 0.912–7.7971, p = 0.0409) were determinants of OS. Presence of PSA response (HR 0.186, 95 % CI 0.079–0.439, p < 0.0001) and presence of visceral disease (HR 5.891, 95 % CI 1.43–24.267, p = 0.0126) were determinants of PFS.

Post-chemo Group. In multivariate analysis, presence of PSA response (HR 0.213, 95 % CI 0.076–0.592, p = 0.0001), Gleason score of ≥ 8 (HR 2.658, 95 % CI 1.13–6.251, p = 0.0186) and PSA-DT of < 2 months (HR 3.006, 95 % CI 1.278–7.07, p = 0.0289) were determinants of OS, while presence of PSA response (HR 0.403, 95 % CI 0.203–0.797, p = 0.0007) was a determinant of PFS (Table 5).

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