Rhonda L Bitting1, Patrick Healy2, Daniel J George3, Monika Anand4, Sung Kim5, Tina Mayer5, Carol Winters4, Colleen Riggan4, Julia Rasmussen4, Rhonda Wilder4, Mark Stein5, Bart Frizzell1, Michael R Harrison3, Tian Zhang3, William R Lee6, Yuan Wu2, Bridget F Koontz6, Andrew J Armstrong7. 1. Comprehensive Cancer Center of Wake Forest University, Departments of Internal Medicine and Radiation Oncology, Winston-Salem NC USA. 2. Department of Biostatistics, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA. 3. Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Surgery, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Pharmacology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Cancer Biology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA. 4. Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham NC, USA. 5. Cancer Institute of New Jersey, Rutgers, NJ, USA. 6. Department of Radiation Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA. 7. Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Surgery, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Pharmacology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Cancer Biology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA. Electronic address: andrew.armstrong@duke.edu.
Abstract
BACKGROUND: Salvage external beam radiotherapy (RT) with androgen deprivation therapy (ADT) improves survival over RT in men with prostate cancer (PC) and rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP). OBJECTIVE: To investigate the safety and efficacy of enzalutamide concurrent with salvage RT and ADT. DESIGN, SETTING, AND PARTICIPANTS: This was a three-center prospective phase 2 single-arm trial (NCT02057939) of men with Gleason 7-10 PC and PSA recurrence within 4 yr of RP ranging from 0.2 to 4.0 ng/dl, no prior hormonal therapy, and no radiographic evidence of metastases. We enrolled 38 men; 37 completed therapy and were evaluable with testosterone recovery at 2 yr. INTERVENTION: Six months of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was improved 2-yr progression-free survival (PFS) over historical controls. Secondary objectives included 3-yr PFS, safety, and patient-reported quality of life (QOL). RESULTS AND LIMITATIONS: The primary endpoint of 2-yr PFS was 65% (95% confidence interval [CI]: 47, 78) versus 51% (95% CI: 33, 67) in a trial of men with similar eligibility treated with salvage RT and adjuvant docetaxel. The 3-yr PFS was 53%. Eleven (29%) men experienced G3 toxicities, and there were no G4-5 or unexpected toxicities. QOL data suggest modest worsening of bowel, bladder, and hormonal symptoms at 3 mo, with recovery by 24 mo in most men. CONCLUSIONS: Salvage RT with enzalutamide and ADT following RP for men with PSA recurrent high-risk PC is safe and demonstrates encouraging efficacy, warranting prospective controlled phase 3 trials of ADT with or without potent androgen receptor inhibition in this curative-intent setting. PATIENT SUMMARY: Addition of 6 mo of oral daily enzalutamide to standard salvage radiation and hormone therapy is safe and may improve prostate cancer remission rates at 2 and 3 yr.
BACKGROUND: Salvage external beam radiotherapy (RT) with androgen deprivation therapy (ADT) improves survival over RT in men with prostate cancer (PC) and rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP). OBJECTIVE: To investigate the safety and efficacy of enzalutamide concurrent with salvage RT and ADT. DESIGN, SETTING, AND PARTICIPANTS: This was a three-center prospective phase 2 single-arm trial (NCT02057939) of men with Gleason 7-10 PC and PSA recurrence within 4 yr of RP ranging from 0.2 to 4.0 ng/dl, no prior hormonal therapy, and no radiographic evidence of metastases. We enrolled 38 men; 37 completed therapy and were evaluable with testosterone recovery at 2 yr. INTERVENTION: Six months of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was improved 2-yr progression-free survival (PFS) over historical controls. Secondary objectives included 3-yr PFS, safety, and patient-reported quality of life (QOL). RESULTS AND LIMITATIONS: The primary endpoint of 2-yr PFS was 65% (95% confidence interval [CI]: 47, 78) versus 51% (95% CI: 33, 67) in a trial of men with similar eligibility treated with salvage RT and adjuvant docetaxel. The 3-yr PFS was 53%. Eleven (29%) men experienced G3 toxicities, and there were no G4-5 or unexpected toxicities. QOL data suggest modest worsening of bowel, bladder, and hormonal symptoms at 3 mo, with recovery by 24 mo in most men. CONCLUSIONS: Salvage RT with enzalutamide and ADT following RP for men with PSA recurrent high-risk PC is safe and demonstrates encouraging efficacy, warranting prospective controlled phase 3 trials of ADT with or without potent androgen receptor inhibition in this curative-intent setting. PATIENT SUMMARY: Addition of 6 mo of oral daily enzalutamide to standard salvage radiation and hormone therapy is safe and may improve prostate cancer remission rates at 2 and 3 yr.
Authors: Kevin Shee; Claire M de la Calle; Albert J Chang; Anthony C Wong; Felix Y Feng; Alexander R Gottschalk; Peter R Carroll; Hao G Nguyen Journal: Adv Radiat Oncol Date: 2022-03-12
Authors: Karen A Autio; Emmanuel S Antonarakis; Tina M Mayer; Daniel H Shevrin; Mark N Stein; Ulka N Vaishampayan; Michael J Morris; Susan F Slovin; Elisabeth I Heath; Scott T Tagawa; Dana E Rathkopf; Matthew I Milowsky; Michael R Harrison; Tomasz M Beer; Arjun V Balar; Andrew J Armstrong; Daniel J George; Channing J Paller; Arlyn Apollo; Daniel C Danila; Julie N Graff; Luke Nordquist; Erica S Dayan Cohn; Kin Tse; Nicole A Schreiber; Glenn Heller; Howard I Scher Journal: Eur Urol Open Sci Date: 2021-11-17