The STARTAR Phase 2 Trial: Salvage RT Plus ADT/Apalutamide and Docetaxel

Androgen deprivation therapy (ADT) paired with salvage radiation therapy (RT) is known to improve survival for patients with prostate-specific antigen (PSA)-recurrent prostate cancer after radical prostatectomy (RP).

Knowing that docetaxel improves survival rates in patients with metastatic hormone-sensitive prostate cancer, Tian Zhang, MD, MHS, and colleagues evaluated a combination of salvage RT, ADT/apalutamide, and docetaxel in the STARTAR phase 2 trial. Results of the trial will be presented at the American Society of Clinical Oncology 2023 Annual Meeting.

The multicenter, investigator-initiated, phase 2 trial enrolled 39 patients with recurrent prostate cancer post-RP between March 2018 and February 2020. As of the December 2022 data cutoff, 54% of patients had Gleason 7 prostate cancer, while 46% of patients had Gleason 8 to 10 prostate cancer. The median follow-up was 36 months.

Patients were given ADT with apalutamide for 9 months and RT beginning week 8 (66-74 Gy to the prostate bed +/- pelvic lymph nodes over 6-8 weeks). Patients then completed 6 cycles of concurrent docetaxel (75 mg/m² q3 weeks). The primary end point was 36-month progression-free survival (PFS), defined as a composite of freedom from PSA >0.2 plus post-RT nadir with subsequent rise, clinical progression, other therapy start, or death, among patients with testosterone recovery (>100 ng/dL). Kaplan-Meier estimates for PFS were used to determine landmark 24-month and 36-month rates and were compared with PFS rates from prior trials using a binomial test.

Of all patients, 3% were lymph node-positive. The median PSA was 0.58 ng/mL (range, 0.21-3.40), and the median time from RP was 7.6 months (range, 2-98 months). A total of 37 patients (95%) completed at least 1 cycle of docetaxel, while 23 patients (62%) completed all 6 cycles. All patients achieved undetectable PSA nadirs. The PFS rates were 84% at 24 months and 72% at 36 months; 95% of patients recovered testosterone at 36 months. Compared with the 40% historical PFS rate and 53% PFS rate from the STREAM trial, the 72% 36-month PFS rate was statistically significantly improved (P<.001 and P=.013, respectively). Any-grade adverse events included hot flashes, fatigue, alopecia, dysgeusia, rash, and febrile neutropenia.

This initial phase 2 trial of ADT, apalutamide, salvage RT, and 6 docetaxel cycles for high-risk PSA recurrence improved the 3-year PFS rate to 72%. Future studies utilizing intensified systemic treatments in the nonmetastatic hormone-sensitive but high-risk salvage setting may be feasible, with fewer patients experiencing cancer progression over time.