Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer

Pedro C Lara; Juan I Rodríguez-Melcón; Amalia Palacios-Eito; Antonio Lozano; Asunción Hervás-Morón; Elena Villafranca; Alfonso Gómez-Iturriaga; Gemma Sancho; Xavier Maldonado

doi:10.3389/fonc.2022.891886

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer

Front Oncol. 2022 Jul 14:12:891886. doi: 10.3389/fonc.2022.891886. eCollection 2022.

Authors

Pedro C Lara¹, Juan I Rodríguez-Melcón², Amalia Palacios-Eito³, Antonio Lozano⁴, Asunción Hervás-Morón⁵, Elena Villafranca⁶, Alfonso Gómez-Iturriaga⁷, Gemma Sancho⁸, Xavier Maldonado⁹

Affiliations

¹ Canarian Comprehensive Cancer Center, San Roque University Hospital, Fernando Pessoa Canarias University, Las Palmas, Spain.
² Radiation Oncology. Dr. Negrín University Hospital, Las Palmas, Spain.
³ Radiation Oncology, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain.
⁴ Radiation Oncology, Virgen de la Arriexaca University Hospital, Murcia, Spain.
⁵ Radiation Oncology, Ramon y Cajal University Hospital, Madrid, Spain.
⁶ Radiation Oncology, Navarra University Hospital, Pamplona, Spain.
⁷ Radiation Oncology, Cruces University Hospital, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
⁸ Radiation Oncology, San Creu I San Pau University Hospital, Barcelona, Spain.
⁹ Radiation Oncology, Vall d´Hebron University Hospital, Barcelona, Spain.

Abstract

Background: Intermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia.

Objective: This study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer.

Method: This trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8-12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes.

Results: Sixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs).

Conclusion: Enzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials.

Keywords: enzalutamide monotherapy; hypofractionated; intermediate risk; prostate cancer; radiotherapy.