Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study.

Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation.

These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models.

Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 [95% confidence interval: 0.53-0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40-1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33-1.44]; p = 0.32) and metachronous/low-volume (0.22 [0.09-0.55]; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease.

TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC.


European journal of cancer (Oxford, England : 1990). 2023 Aug 11 [Epub ahead of print]

Axel S Merseburger, Neeraj Agarwal, Amitabha Bhaumik, Florence Lefresne, Laurence I Karsh, Andrea J Pereira de Santana Gomes, Álvaro Juárez Soto, Robert W Given, Sabine D Brookman-May, Suneel D Mundle, Sharon A McCarthy, Hirotsugu Uemura, Simon Chowdhury, Kim N Chi, Anders Bjartell

University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Electronic address: ., Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Suite 5726, Salt Lake City, UT 84112, USA. Electronic address: ., Janssen Research & Development, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA. Electronic address: ., Janssen Research & Development, 1400 McKean Road, Spring House, PA 19477, USA. Electronic address: ., The Urology Center of Colorado, 2777 Mile High Stadium Circle, Denver, CO 80211, USA. Electronic address: ., Liga Norte Riograndense Contra O Cancer, Av Miguel Castro, 1355, Dix-Sept Rosado, Natal 59075-740, Brazil. Electronic address: ., Hospital Universitario de Jerez de la Frontera, Ronda de Circunvalación s/n, 11407 Jerez de la Frontera, Cádiz, Spain. Electronic address: ., Urology of Virginia, Eastern Virginia Medical School, 825 Fairfax Ave., Suite 310, Norfolk, VA 23507, USA. Electronic address: ., Janssen Research & Development, 1400 McKean Road, Spring House, PA 19477, USA; Ludwig-Maximilians-University, Geschwister-Scholl-Platz 1, D-80539 München, Germany. Electronic address: ., Janssen Research & Development, 700 US Highway 202 S, Raritan, NJ 08869, USA. Electronic address: ., Janssen Research & Development, 700 US Highway 202 S, Raritan, NJ 08869, USA. Electronic address: ., Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osakasayama, Osaka 589-8511, Japan. Electronic address: ., Guy's, King's, and St Thomas' Hospitals, Great Maze Pond, London SE1 9RT, UK; Sarah Cannon Research Institute, 93 Harley St, Marylebone, London W1G 6AD, UK. Electronic address: ., BC Cancer and Vancouver Prostate Centre, 600 West 10th Avenue, Vancouver V5Z 1L3, British Columbia, Canada. Electronic address: ., Skåne University Hospital, Lund University, Jan Waldenströms gata 5, plan 2, 20502 Malmö, Sweden. Electronic address: .