Prof. Lei Wang: Comparison of first-line treatment regimens for metastatic hormone-sensitive prostate cancer—update and review

On January 8, the "2022 Beijing Urological Cancer Youth Forum" was successfully held by the Youth Committee of the Urology and Male Genital Oncology Committee of the Beijing Anti-Cancer Association and the Beijing Medical Award Foundation
.

Prof.
Lei Wang from Shougang Hospital of Peking University interpreted the update of the research related to the first-line treatment of metastatic hormone-sensitive prostate cancer (mHSPC), and reviewed and analyzed the previous research data
.

The medical pulse is organized as follows for the readers
.

Updated Study Interpretation ARCHES is a double-blind, placebo-controlled Phase III clinical study designed to evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy (ADT) in patients with mHSPC
.

At ESMO 2021, the ARCHES study announced final overall survival (OS) results
.

The results showed that at a median follow-up of 44.
6 months, compared with placebo+ADT, enzalutamide+ADT could significantly improve OS and reduce the risk of death by 34% in the ITT population (HR=0.
66, P<0.
001)
.

The 48-month OS rates were 71% and 57% in the enzalutamide+ADT group and the placebo+ADT group, respectively
.

The TITAN study is similar to the ARCHES design, and the final results of the 2021 TITAN study will be published in the journal JCO
.

The results showed that compared with placebo + ADT, apalutamide + ADT can significantly improve the OS of mHSPC patients, and the median OS of apalutamide group and placebo group was not reached and 39.
8 months, respectively (HR=0.
52, P < 0.
0001)
.

Previous research review and meta-analysis Based on the results of these two large-scale studies, Professor Wang reviewed and interpreted a meta-analysis that summarized the results of multiple previous studies
.

The GETUG-AFU15, CHAARTED, STAMPEDE study arm C was a first-line study of docetaxel + ADT vs placebo in mHSPC
.

The GETUG-AFU15 study from France in 2004 showed that docetaxel did not benefit the general population, but docetaxel could benefit OS in high-risk groups
.

In 2006, the CHAARTED study from the United States established the status of docetaxel in the treatment of mHSPC.
This study first proposed the concepts of high tumor burden and low tumor burden
.

Two studies of abiraterone in mHSPC include the LATITUDE and STAMPEDE study arm
G.

The LATITUDE study mainly enrolled high-risk patients, and the high tumor burden population accounted for 80% (based on the CHAARTED study definition)
.

The STAMPEDE study arm G showed good OS results for abiraterone in both the total population and the high-risk population (55%)
.

The ENZAMET, ARCHES, TITAN studies are about novel androgen receptor antagonists for the treatment of mHSPC
.

At the beginning of the design of these studies, docetaxel has entered the first-line treatment of mHSPC.
Therefore, a certain proportion of patients in each study have received docetaxel treatment at the time of enrollment
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In addition, the unique design of the ENZAMET study was that approximately 44.
7% allowed continued (concurrent) use of docetaxel chemotherapy at or after enrollment
.

A later analysis suggested that this may have affected the results of enzalutamide
.

The ARCHES and TITAN studies are global studies with broader enrollment
.

Radiation + ADT studies have two related studies: STAMPEDE-radio and HORRAD studies
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STAMPEDE-radio suggests that radiotherapy + ADT can improve the OS benefit of patients with low tumor burden, while the general population and patients with high tumor burden have no obvious OS benefit
.

Results from the HORRAD study (high tumor/low tumor burden as defined by the investigator) were similar to the STAMPEDE-radio study
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The pooled analysis showed that in terms of OS benefit, the pooled HR of GETUG-AFU15, CHAARTED, STAMPEDE study arm C was 0.
79; LATITUDE and STAMPEDE study arm G pooled HR was 0.
64; ENZAMET, ARCHES, TITAN study pooled HR was 0.
66, while this Statistical analysis of several studies excluding docetaxel-treated patients found a pooled HR of 0.
60 for the three studies; pooled HR for the STAMPEDE-radio and HORRAD studies was 0.
92
.

Concomitant or prior docetaxel treatment may attenuate the efficacy of newer endocrine therapies, the study found
.

As shown, the HR was 0.
60 for patients who received novel endocrine therapy without prior docetaxel, and the pooled HR for novel endocrine therapy was 0.
88 for patients previously treated with docetaxel
.

Prof.
Lei Wang conducted a meta-analysis of ENZAMET, ARCHES, TITAN and SEAMPED-radio studies (excluding patients who received docetaxel in the past)
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The efficacy of ADT, docetaxel + ADT, abiraterone + ADT, novel endocrine therapy + ADT and radiotherapy + ADT in various populations was mainly evaluated
.

In the total population of the meta-analysis of the 4 studies, compared with ADT, the HRs of docetaxel+ADT, abiraterone+ADT, novel endocrine therapy+ADT, and radiotherapy+ADT were 0.
79, 0.
64, 0.
61, and 0.
92, respectively.
Endocrine therapy is the best; in the high tumor burden population, the HRs of these four therapies are 0.
73, 0.
61, 0.
68, and 1.
1, respectively, and abiraterone is the best; in the low tumor burden population, the HRs of these four therapies are 0.
91, respectively , 0.
68, 0.
53, 0.
68, the new endocrine therapy is the best
.

Among patients with visceral metastases, the HRs of docetaxel + ADT, abiraterone + ADT, and new endocrine therapy + ADT were 0.
53, 0.
58, and 0.
95, respectively, and docetaxel was the best
.

The safety analysis of the two studies published in JAMA ONCOLOGY and JU showed similar results, suggesting that both apalutamide and enzalutamide have better safety profiles in terms of serious adverse events
.

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