Phase 3 INDICATE Trial Evaluating the Use of Apalutamide in Patients with Biochemical Recurrence of Prostate Cancer

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Prostate cancer will be diagnosed in approximately 248,530 men in the United States in 2021.1 Localized prostate cancer treatment options include radical prostatectomy, cryotherapy, brachytherapy, radiation therapy, and surveillance.2 With radical prostatectomy, approximately 20% to 40% of patients will experience a biochemical recurrence (BCR) necessitating further treatment.2 The standard of care, salvage therapy, is radiation therapy of the prostate bed and pelvic lymph nodes along with short-term androgen deprivation therapy.2 BCR is diagnosed using serum prostate-specific antigen (PSA) levels posttreatment, with current guidelines defining BCR after radical prostatectomy as a PSA value of ≥0.2 ng/mL after an initial PSA value of ≥0.2 ng/mL taken 6 weeks after radical prostatectomy.3

At the 2021 American Society of Clinical Oncology annual meeting, Vapiwala and colleagues presented information on patient eligibility and trial methods on the Phase III Study of Local or Systemic Therapy Intensification Directed by PET in Prostate Cancer Patients with Post-Prostatectomy Biochemical Recurrence (INDICATE). The trial is evaluating the use of apalutamide with or without targeted radiation therapy and comparing this therapy to standard of care in patients with BCR after radical prostatectomy and investigating whether the use of apalutamide can prolong progression-free survival.4 The study’s primary end point is the time from enrollment to progression to symptomatic disease, radiographic progression on conventional imaging, or death.

A total of 804 patients who have BCR of prostate cancer after radical prostatectomy will be enrolled in the trial. BCR in this trial is defined as PSA >0.2 ng/mL if the participant is within 12 months of radical prostatectomy or a PSA >0.5 ng/mL. Along with this PSA level, the participant must not have metastases on conventional imaging and will be eligible for standard-of-care salvage therapy. Before trial enrollment, a baseline positron emission tomography (PET) will be performed to determine in which of the 2 study cohorts the patients will be placed. Cohort 1 will enroll 480 patients who are PET-negative, and cohort 2 will consist of 324 patients who are PET-positive for metastases outside of the pelvis. Patients in cohort 1 will be randomized to treatment with standard-of-care salvage therapy with or without apalutamide. The patients in cohort 1 will be randomized to 85% power to distinguish the 5-year progression-free survival rate of 90% for participants receiving apalutamide versus 80% in participants receiving standard-of-care salvage therapy only. Participants placed into cohort 2 will be randomized to standard-of-care salvage therapy and apalutamide with or without metastasis-directed radiation therapy to PET-positive lesions. As in cohort 1, these participants will be randomized with 85% power to distinguish the 5-year progression-free survival rate of 76.5% for participants receiving apalutamide versus 61.5% in the participants receiving standard-of-care salvage therapy only.

The secondary end points in this study are toxicity, overall survival and event-free survival, and PET progression.

References

  1. American Cancer Society. Key statistics for prostate cancer. Updated January 12, 2021. www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed September 20, 2021.
  2. Vapiwala N, Chen YH, Cho SY, et al. Phase III study of local or systemic therapy INtensification DIrected by PET in prostate CAncer patients with post-prostaTEctomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191. J Clin Oncol. 2021;39:15_suppl.
  3. McCormick BZ, Mahmoud AM, Williams SB, Davis JW. Biochemical recurrence after radical prostatectomy: current status of its use as a treatment endpoint and early management strategies. Indian J Urol. 2019;35:6-17.
  4. ClinicalTrials.gov. Treating prostate cancer that has come back after surgery with apalutamide and targeted radiation using PET/CT imaging (NCT04423211). Updated March 8, 2021. https://clinicaltrials.gov/ct2/show/NCT04423211. Accessed September 20, 2021.

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