Abiraterone vs docetaxel in Asian mHSPC patients: What’s the difference?

A real-world analysis of 574 Asian patients with metastatic hormone-sensitive prostate cancer (mHSPC) demonstrated a significantly longer progression-free survival (PFS) and similar overall survival (OS) with abiraterone plus androgen deprivation therapy (ADT) vs docetaxel plus ADT.

Both abiraterone acetate plus ADT and docetaxel plus ADT are current treatment options for mHSPC. In Hong Kong, docetaxel and abiraterone were approved for use in mHSPC patients in 2015 and 2019, respectively.

Data on 574 mHSPC patients who began treatment with docetaxel or abiraterone in addition to ADT between 2015 and 2021 were collected from all seven public oncology centers in Hong Kong. [Clin Genitourin Cancer 2024;doi:10.1016/j.clgc.2023.07.012] “To our knowledge, the present study is the largest real-world comparative analysis of mHSPC patients receiving abiraterone or docetaxel in combination with ADT,” wrote the researchers from the Chinese University of Hong Kong (CUHK).

Of the 574 patients, 73.0 percent received docetaxel and 27.0 percent received abiraterone. The standard dose for docetaxel was 75 mg/m² of body surface area for ≤6 cycles, but >6 cycles could be given if tolerated. Abiraterone was given at 1,000 mg daily with prednisolone 5 mg, until disease progression or unacceptable toxicity.

The median age was higher in the abiraterone vs docetaxel group (72.5 years vs 66.3 years). In patients who received abiraterone, 11.6 percent had an Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥2, vs 5.5 percent in the docetaxel group.

Efficacy

The median follow-up period was 23.8 months and 17.3 months in the docetaxel and abiraterone groups, respectively. At the data cut-off, 73.0 percent and 33.5 percent of patients in the docetaxel and abiraterone groups, respectively, experienced disease progression or died. Median PFS was 15.1 months in the docetaxel group vs not reached (NR) in the abiraterone group (p<0.001).

Subsequent therapies were more commonly used in the docetaxel group (64.2 percent) than in the abiraterone group (23.9 percent). “This may be attributable to fewer abiraterone-treated patients experiencing progression. Another possible explanation is that patients who received abiraterone were older, making the switch to other subsequent therapies [eg, chemotherapy] even more challenging,” suggested the researchers.

Despite the comparatively inferior baseline features and lower rate of subsequent therapies, OS with abiraterone was found to be similar to that with docetaxel (median OS, NR vs 66.3 months; p=0.58). “In the docetaxel arm, additional treatment beyond 6 cycles did not affect median OS,” noted the researchers.

PSA kinetics

A ≥90 percent decline in prostate-specific antigen (PSA) level (PSA90) was achieved at 3 months by 74.0 percent of patients on abiraterone vs 26.2 percent of patients on docetaxel (p<0.001). This difference in PSA90 between the two groups was maintained at 6 months, with 82.0 percent and 34.6 percent of patients in the abiraterone and docetaxel arms achieving PSA90, respectively (p<0.001).

For the entire cohort, patients who achieved PSA90 at 3 months had longer median PFS (27.1 months vs 14.5 months; p<0.001) and median OS (NR vs 58.5 months; p<0.001) than those who did not. This association between PSA90 at 3 months and improved survival outcomes was observed separately in both the docetaxel and abiraterone groups.

Similarly, patients who achieved an undetectable PSA nadir (<0.1 ng/mL) had longer PFS and OS than those who did not (≥0.1 ng/mL) (PFS, 53.6 months vs 13.2 months; p<0.001; OS, NR vs 48.4 months; p<0.001). This association was significant (p<0.001) in both the docetaxel and abiraterone groups.

“Failure to achieve PSA90 at 3 months and failure to achieve an undetectable PSA nadir were significantly associated with unfavourable survival, and may be useful prognostic indicators for early treatment intensification,” suggested the researchers.

Toxicity

Febrile neutropenia (FN), which is a potentially life-threatening condition, occurred in 12.2 percent of patients in the docetaxel group vs no patients in the abiraterone group. Pre-emptive use of granulocyte-colony stimulating factor (GCSF) was reported in 39.1 percent of patients treated with docetaxel. The rate of FN was lower in patients who received primary GCSF (9.1 percent) than those who did not (14.1 percent).

“Since the use of primary GCSF can effectively reduce FN incidence in mHSPC and metastatic castration-resistant prostate cancer patients treated with docetaxel, pre-emptive use of GCSF is highly recommended,” advised the researchers. [Asia Pac J Clin Oncol 2021;17:39-47]

A higher rate of any-grade anaemia was also observed in the docetaxel vs abiraterone group (95.5 percent vs 70.3 percent). Any-grade neuropathy occurred in 23.9 percent of docetaxel-treated patients vs no patients in the abiraterone group. “These reflect the suboptimal tolerance to chemotherapy in Asian prostate cancer patients. Because of the elevated risk of chemotherapy-related toxicities among Asian populations, use of abiraterone over chemotherapy is encouraged in some Asian countries,” noted the researchers. [Cancers (Basel) 2022:14:407; Asia Pac J Clin Oncol 2022;18:686-695]

Any-grade hypertension was more common in the abiraterone than docetaxel group (61.9 percent vs 17.4 percent), as was any-grade hypokalaemia (21.3 percent vs 5.7 percent) and grade ≥3 alanine transaminase (ALT) increase (1.9 percent vs 0.2 percent). Discontinuation due to toxicity occurred more commonly with docetaxel than with abiraterone treatment (3.6 vs 0.6 percent).

“For Asian mHSPC patients, upfront abiraterone plus ADT may be preferred over docetaxel plus ADT for the longer PFS and lower risk of chemotherapy-related toxicities,” concluded the researchers.