The TITAN Trial in mCSPC


Ralph V. Boccia, MD: The phase 3 TITAN trial was conducted in men with castration-sensitive metastatic prostate cancer. Patients who were randomized to receive the old standard of care, which was androgen deprivation therapy [ADT], vs the experimental arm, which was androgen deprivation therapy plus apalutamide. This was a randomized double-blind trial. It was androgen deprivation therapy plus apalutamide vs androgen deprivation therapy plus placebo—a placebo-controlled trial.

Men were risk stratified based on their volume of disease, whether they had had prior therapy and whether they had received prior chemotherapy with docetaxel. Patients were then given either androgen deprivation therapy plus placebo or androgen deprivation therapy plus apalutamide, 240 mg once a day, which is the approved dosage that we use in clinic today. Patients were then monitored with radiographic scans and PSA [prostate-specific antigen].

The coprimary end points were overall survival and radiographic progression-free survival, to see how long patients went with therapy and no progression of their scans, whether bone or CT scans. The secondary end point was the time to needing chemotherapy—how long could patients be treated with endocrine therapy alone before they progressed, became castrate resistant, and required cytotoxic chemotherapy. Those were the end points we used in that clinical trial to determine efficacy and see whether this drug was worth introducing into clinic via the FDA-approval mechanism.

Responses were seen both in the primary end points as well as the secondary end points. This trial met its primary and secondary end points for overall survival. The risk of death was decreased by 33% in the patients treated with apalutamide plus ADT vs those patients treated with placebo plus ADT. That’s a hazard ratio of 0.67, a 33% reduction in the risk of death. The other coprimary end point was the radiographic progression-free survival, and this delayed by 51% progression on x-rays. Of those coprimary end points, it also met—as I just mentioned—its secondary end point, which was time to requiring chemotherapy. There was a 61% reduction in the risk of needing chemotherapy on the apalutamide-plus-ADT arm compared with the placebo-plus-ADT arm. It met all 3 of its primary and secondary end points.

Based on the data you just heard, the prognosis of patients with high-volume disease, most all of us would recommend that as soon as metastatic castration-sensitive disease is diagnosed, the patient ought to be put on combination therapy with apalutamide and androgen deprivation therapy, certainly supported by the TITAN trial or at least considered for it.

Transcript edited for clarity.

Case: A 66-Year-Old Male with Metastatic Castrate-Sensitive Prostate Cancer

Initial presentation

  • A 66-year-old man presented with mild intermitted back pain
  • PMH: DM; medically controlled; OTC analgesics for pain
  • FH: No known family history of cancer
  • PE: DRE revealed an enlarged prostate; otherwise unremarkable

Clinical Workup

  • PSA 70 ng/mL
  • Core needle biopsy with TRUS showed adenocarcinoma of prostate
    • Gleason score (4+4)
  • Bone scan revealed 4 spinal lesions (T8/T9, L1/L2) and 1 in the right femur
  • Chest/abdominal/pelvic CT scan was negative for distant metastases
  • Diagnosis: stage IV mCSPC
  • ECOG PS 1

Treatment and Follow-Up

  • He was started on ADT + apalutimide 240 mg qDay
  • At 2-month follow up: PSA 10 ng/mL
  • No new lesions on repeat imaging
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