Table of Contents

• Overview of the Apalutamide trials
• Trial types, phases, and study size
• Conditions and patient groups being studied
• Treatment plans and study comparisons
• Main endpoints and what they mean
• Selected trials in more detail
• What patients may want to know

Overview of the Apalutamide trials

Clinical trials with Apalutamide are focused on prostate cancer in many stages, from high-risk localized disease to advanced metastatic disease.^[1] The studies are testing whether Apalutamide can improve cancer control, delay progression, and support better outcomes when used alone or with other treatments.^[1][2]

Across the trial list, Apalutamide is studied in men after radical prostatectomy, in men with recurrent disease, and in men with hormone-sensitive or castration-resistant disease.^{[1][2] Some studies also include special imaging groups, such as PSMA PET-positive patients, or patients with a poor PSA response after starting treatment.[3][4]}

Trial types, phases, and study size

Most of the trials are interventional, which means the study team gives a treatment and then measures the results.^[1] The set includes both Phase 2 and Phase 3 studies, with Phase 2 trials usually looking at early signs of benefit and Phase 3 trials comparing larger treatment groups.^[1][2]

The enrollment numbers vary a lot, from small studies with 20 or 41 participants to large studies with more than 1,900 participants.^{[5][6] This wide range shows that Apalutamide is being tested in both focused pilot studies and large confirmatory trials.[5][6]}

Conditions and patient groups being studied

Several trials study high-risk localized or locally advanced prostate cancer, which means the cancer is still near the prostate but has features that make it more likely to return or spread.^{[7][6] Other trials focus on disease that has come back after surgery, including biochemical relapse, where PSA rises even before scans show clear spread.[8][9]}

Advanced disease is also a major focus, including metastatic hormone-sensitive prostate cancer, metastatic hormone-naïve prostate cancer, and castration-resistant prostate cancer.^{[2][10][11] Some studies look at low-volume or low-burden metastatic disease, meaning the cancer has spread but the amount of spread is limited.[4][12]}

A few trials use imaging or other response rules to choose patients, such as PSMA PET-positive disease or a PSA level below 0.2 ng/mL after initial treatment.^{[3][4][13] This means the studies are not only asking whether Apalutamide works, but also which patients may benefit most from it.[3][13]}

Treatment plans and study comparisons

Apalutamide is often tested with androgen deprivation therapy (ADT), which lowers male hormones that can feed prostate cancer growth.^{[1][14] In some trials, it is compared with placebo, and in others it is compared with standard hormone treatment, radiotherapy, surgery-related treatment, or other anti-androgen drugs.[2][7][6]}

Several studies also test treatment combinations, such as Apalutamide plus radiotherapy, Apalutamide plus ADT, or Apalutamide with surgery-related care before or after radical prostatectomy.^{[8][9][13] One study looks at intermittent treatment, where hormonal therapy may be stopped and restarted later, instead of being given continuously.[4][4]}

Some trials do not study Apalutamide alone, but include it among several treatment choices for prostate cancer, allowing comparison with other agents such as enzalutamide, abiraterone, or darolutamide.^{[10][11][15] This helps researchers see whether Apalutamide fits best in a particular treatment strategy.[10][15]}

Main endpoints and what they mean

The main study goals, called endpoints, are different from trial to trial, but many focus on how long the cancer stays controlled.^{[1][2] Common endpoints include radiographic progression-free survival, metastasis-free survival, progression-free survival, event-free survival, and overall survival.[1][2][7][6]}

Some studies measure PSA response, such as reaching PSA below 0.2 ng/mL or a confirmed PSA decline, because PSA is a blood marker used to follow prostate cancer.^{[3][4][12] Other studies measure quality of life, sexual function, hot flashes, operability before surgery, or treatment toxicity, which means side effects that are important enough to affect daily life or treatment plans.[1][4][9][16]}

A few trials use more specialized endpoints, such as pathological complete response after surgery, PSMA-PET metastatic progression-free survival, or disease control rate at a set time point.^{[6][13][17] These endpoints help show whether treatment is changing the cancer in a way that can be measured by scans, surgery results, or blood tests.[6][17]}

Selected trials in more detail

NCT04181203 studies Apalutamide with radiotherapy and hormone therapy after biochemical relapse following radical prostatectomy.^[9] The main endpoint is 5-year progression-free survival, so the trial asks whether this combination can keep the cancer controlled longer after surgery has already been done.^[9]

2023-506153-38-00 tests Apalutamide plus ADT before and after radical prostatectomy with pelvic lymph node dissection in high-risk localized or locally advanced disease.^[6] It measures pathological complete response and metastasis-free survival, which gives information about both surgery findings and longer-term cancer spread.^[6]

2022-502686-24-00 looks at intermittent ADT with Apalutamide monotherapy in metastatic castration-sensitive prostate cancer.^[4] It measures 18-month radiographic progression-free survival and hot flash burden, so it is studying both cancer control and a symptom that can affect comfort and daily life.^[4]

2023-508607-20-00 compares Apalutamide plus ADT with ADT alone in metastatic hormone-sensitive prostate cancer.^[10] Its main outcomes are radiographic progression-free survival and overall survival, which are key measures of whether the added treatment improves disease control and life length.^[10]

2023-505852-23-00 studies Apalutamide with radiotherapy and an LHRH agonist in high-risk recurrent prostate cancer after radical prostatectomy, using PSMA-PET metastatic progression-free survival as the main endpoint.^[13] This means the study is trying to see whether adding Apalutamide can delay spread seen on a sensitive scan or delay death.^[13]

NCT04295447 focuses on men with high-risk prostate cancer after radical prostatectomy and measures progression-free survival.^[8] This trial is asking whether adjuvant Apalutamide, meaning treatment given after surgery, can delay recurrence or spread compared with standard care.^[8]

2024-517901-97-00 studies ADT with Apalutamide and stereotactic radiotherapy in localized or locally advanced high-risk prostate cancer.^[16] The main endpoint is the 5-year biochemical control rate, and safety is also measured through gastrointestinal and genitourinary toxicity, which means bowel and urinary side effects.^[16]

What patients may want to know

People joining these studies are usually men with prostate cancer who meet specific disease and response criteria.^{[1][4][13] The exact rules differ by trial, so one study may accept men after surgery, while another may require metastatic disease or a PSMA PET-positive scan.[3][8][10]}

Many trials are trying to find out whether Apalutamide can improve the chance of staying free from progression, avoid metastases, or improve survival compared with current care.^{[2][6][10] Others are looking at whether shorter or intermittent treatment can work as well as continuous treatment while reducing treatment burden.[4][4]}

Because the studies use different designs, the results may answer different questions, but together they help show where Apalutamide may fit in prostate cancer care.^[1][15]