Degarelix Therapy for Prostate Cancer in a Real-world Setting

Experience From the German IQUO (Association for Uro-Oncological Quality Assurance) Firmagon Registry

Götz Geiges; Thomas Harms; Gerald Rodemer; Ralf Eckert; Frank König; Rolf Eichenauer; Jörg Schroder

Disclosures

BMC Urol. 2015;15(122) 

In This Article

Results

Patients

A total of 1,010 patients received degarelix and were included. Baseline demographic and disease characteristics of the registry population are summarized in Table 2. Around two-thirds of patients had localized (n = 469) or locally advanced (n = 201) disease (340 had metastatic disease) and almost half had a Gleason score of 8–10. A total of 542 patients had received prior HT, predominantly LHRH agonists (53.7 %); of these, 455 had received prior LHRH analogue therapy (LHRH agonists or GnRH antagonists). Baseline PSA (median 14.27 ng/ml) was ≥20 ng/ml in 43.6 % of patients.

At the time of this report, a total of 401, 158 and 44 patients had received degarelix for 12, 24 and 36 months, respectively; only two patients had received treatment for 48 months, reflecting entry to the register over time, at the time of this analysis.

Reasons for discontinuation of degarelix in patients with documented answers (n = 479) included change in therapy (30.7 %), patient request/others (22.8 %), death (14.2 %), PSA progression (14.4 %), clinical progression (7.5 %), adverse event (6.1 %) or lost to follow-up (4.4 %).

Tumour Response

After 1 year of treatment, among patients with a documented response (n = 221), 19.9 % (n = 44) had complete remission, 19.5 % (n = 43) partial remission, 27.6 % (n = 61) objective stabilization and 21.7 % (n = 48) objective progression; 11.3 % (n = 25) were not evaluable. After 24 months (n = 80), these values were 18.8 % (n = 15), 22.5 % (n = 18), 25.0 % (n = 20), 22.5 % (n = 18) and 11.3 % (n = 9), respectively. After 36 months, (n = 23), these values were 34.8 % (n = 8), 17.4 % (n = 4), 21.7 % (n = 5), 26.1 % (n = 6) and 0 % (n = 0), respectively. Patient responses over time are summarized in Fig. 1 .

Figure 1.

Patient response to treatment over time

Overall Survival

In total, 212 of 1,010 patients died and 51 were lost to follow-up. The median OS (all patients) had not yet been reached; the 75th percentile value (i.e. where 25 % of patients had reached event) was 148.9 weeks. While the median OS had also not yet been reached in patients with or without prior HT, the 75th percentile value was longer for those without prior HT (176.4 weeks) compared with those with prior HT (131.7 weeks). A Cox regression analysis showed patients who received prior HT (n = 542) had a 58 % increased mortality risk (hazard ratio 1.58, 95 % CI 1.20–2.09) compared with patients who had not received prior HT (n = 468) (p = 0.001).

Similarly, median OS had not been reached in patients with or without prior LHRH analogue therapy (LHRH agonist/GnRH antagonist), however, the 75th percentile value was shorter (123.1 weeks) in those who received prior LHRH analogues compared with those who had not (167.4 weeks).

PSA PFS

Of the 1,010 patients in this study, 200 (20 %) experienced PSA progression, 137 patients died, 41 were lost to follow-up and 632 were alive and PSA progression-free. Median PSA PFS was not yet reached; the 75th percentile value for PSA PFS was 59.6 weeks.

Of the 340 patients with metastatic disease, 91 (27 %) experienced PSA progression. Median time to PSA progression (PSA PFS) was 141.4 weeks (75th percentile value 32.4 weeks).

In patients who received prior LHRH analogue therapy (n = 455), median time to PSA progression was shorter (209 weeks [75th percentile value 30.4 weeks]) than in those who had not received prior LHRH analogues (n = 555) where median PSA PFS was not reached (75th percentile value 88.4 weeks). Also, a greater proportion of patients who received prior LHRH analogue therapy (25.05 %; n = 114) experienced PSA progression compared with those who had not (15.5 %, n = 86).

PSA

Overall, degarelix produced a rapid and profound PSA reduction, sustained for up to 36 months (Fig. 2a). A similar PSA profile was observed in patients with baseline metastatic disease (Fig. 2b). PSA suppression was greater and more rapid, and maintenance of PSA suppression more effective, in patients who had not received prior HT compared with those who had received prior HT (Fig. 2c–d).

Figure 2.

Percentage change in median PSA over time in (a) all patients; b patients with metastatic disease at baseline; c patients with prior hormonal therapy; and (d) patients with no prior hormonal therapy

Overall, PSA reduction to ≤ 4 ng/ml was achieved in 65 % of patients at 12 months and 71 % of patients at 24 months (Fig. 3a). These values were lower in patients with metastatic disease (41 % and 63 %, respectively) and patients with baseline PSA ≥20 ng/ml (41 % and 44 %, respectively); (Fig. 3b–c).

Figure 3.

Percentage of patients with PSA ≤ 4 ng/ml over time for (a) all patients; b patients with metastatic disease at baseline; and (c) patients with baseline PSA ≥20 ng/ml

Testosterone

Overall, degarelix produced a rapid and profound reduction in testosterone (an optional measurement), falling to 0.19 ng/mL after 1 month (n = 217). Testosterone suppression <20 ng/mL was sustained for the first 24 months in the all-patient group (median testosterone 0.13 ng/mL at 24 months [n = 18]). Testosterone was also suppressed in patients with baseline metastatic disease: median testosterone level was 0.2 ng/mL after 1 month (n = 92) and 0.13 ng/mL at 12 months (n = 20).

S-ALP

Changes in S-ALP (an optional measurement) over time for patients with metastatic disease (n = 70 at 0 months and n = 11 at 12 months) and those without prior HT (n = 53 at 0 months and n = 11 at 12 months) are summarized in Fig. 4. In the metastatic cohort, S-ALP was suppressed after 6–12 months of treatment. S-ALP suppression was observed after 1 month in patients with no prior HT and this was maintained for up to 12 months.

Figure 4.

Percentage change in median serum alkaline phosphatase over time in (a) patients with metastatic disease at baseline and (b) patients with no prior hormonal therapy

Prostate Volume

Mean prostate volume decreased from 36.83 ml at baseline (n = 85 patients) to 30.32 ml (n = 25) after 3 months and to 26.38 ml after 6 months (n = 16).

Tolerability

The most frequent adverse events recorded in patients included hot flushes (12.9 %), injection site erythema (8.5 %), fatigue (5.2 %) and pain (4.2 %). Adverse events experienced by patients at the first and last data points during degarelix therapy are summarized in Table 3. Apart from a slight increase in the incidence of hot flushes, there were no significant changes in frequency of adverse events between the first and last data points.

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