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.

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.

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

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.

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.

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.

Therapeutic advances in medical oncology. 2023 Mar 03*** epublish ***

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

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