Clinical outcomes of volume of disease on patients receiving enzalutamide versus abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer

Pier Vitale Nuzzo; Francesco Ravera; Calogero Saieva; Elisa Zanardi; Giuseppe Fotia; Andrea Malgeri; Sabrina Rossetti; Loana Bueno Valença; Thiago Martins Oliveira; Charles Vauchier; Ricardo Pereira Mestre; Mikol Modesti; Anna Patrikidou; Sandro Pignata; Giuseppe Procopio; Giuseppe Fornarini; Ugo De Giorgi; Antonio Russo; Edoardo Francini

doi:10.1177/17588359231156147

Clinical outcomes of volume of disease on patients receiving enzalutamide versus abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer

Ther Adv Med Oncol. 2023 Mar 3:15:17588359231156147. doi: 10.1177/17588359231156147. eCollection 2023.

Authors

Pier Vitale Nuzzo¹, Francesco Ravera^{1

2}, Calogero Saieva³, Elisa Zanardi⁴, Giuseppe Fotia⁵, Andrea Malgeri⁶, Sabrina Rossetti⁷, Loana Bueno Valença^{8

9}, Thiago Martins Oliveira^{8

9}, Charles Vauchier¹⁰, Ricardo Pereira Mestre¹¹, Mikol Modesti¹¹, Anna Patrikidou¹², Sandro Pignata⁷, Giuseppe Procopio¹³, Giuseppe Fornarini⁴, Ugo De Giorgi¹⁴, Antonio Russo¹⁵, Edoardo Francini¹⁶

Affiliations

¹ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
² Department of Internal Medicine, University of Genoa, Genova, Italy.
³ Cancer Risk Factors and Lifestyle Epidemiology Unit-ISPRO, Florence, Italy.
⁴ Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁵ Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
⁶ Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy.
⁷ Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
⁸ Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil.
⁹ Hospital Sao Rafael, Salvador, Brazil.
¹⁰ Thoracic Oncology Unit, Bichat-Claude Bernard Hospital, Paris, France.
¹¹ Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.
¹² Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France.
¹³ Oncology Unit, ASST Cremona, Cremona, CR, Italy.
¹⁴ Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST), Meldola, Italy.
¹⁵ Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
¹⁶ Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence 50134, Italy.

Abstract

Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients.

Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA versus Enza for mCRPC.

Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints.

Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1-62.2 months] versus AA (51.6 months; 95% CI, 42.6-60.6 months; p = 0.003). Consistently, those with LV receiving Enza showed increased rPFS (40.3 months; 95 CI, 25.0-55.7 months) than those having AA (22.0 months; 95% CI, 18.1-26.0 months; p = 0.004). No significant difference in OS or rPFS was observed in those with HV treated with AA versus Enza (p = 0.51 and p = 0.73, respectively). In multivariate analysis of patients with LV, treatment with Enza was independently associated with better prognosis than AA.

Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC.

Keywords: abiraterone acetate; enzalutamide; metastatic castration-resistant prostate cancer; overall survival; volume of disease.

Grants and funding

P50 CA211024/CA/NCI NIH HHS/United States