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

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

doi:10.1016/j.ejca.2023.113290

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

Eur J Cancer. 2023 Nov:193:113290. doi: 10.1016/j.ejca.2023.113290. Epub 2023 Aug 11.

Authors

Affiliations

¹ University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Electronic address: [email protected].
² Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Suite 5726, Salt Lake City, UT 84112, USA. Electronic address: [email protected].
³ Janssen Research & Development, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA. Electronic address: [email protected].
⁴ Janssen Research & Development, 1400 McKean Road, Spring House, PA 19477, USA. Electronic address: [email protected].
⁵ The Urology Center of Colorado, 2777 Mile High Stadium Circle, Denver, CO 80211, USA. Electronic address: [email protected].
⁶ Liga Norte Riograndense Contra O Cancer, Av Miguel Castro, 1355, Dix-Sept Rosado, Natal 59075-740, Brazil. Electronic address: [email protected].
⁷ Hospital Universitario de Jerez de la Frontera, Ronda de Circunvalación s/n, 11407 Jerez de la Frontera, Cádiz, Spain. Electronic address: [email protected].
⁸ Urology of Virginia, Eastern Virginia Medical School, 825 Fairfax Ave., Suite 310, Norfolk, VA 23507, USA. Electronic address: [email protected].
⁹ Janssen Research & Development, 1400 McKean Road, Spring House, PA 19477, USA; Ludwig-Maximilians-University, Geschwister-Scholl-Platz 1, D-80539 München, Germany. Electronic address: [email protected].
¹⁰ Janssen Research & Development, 700 US Highway 202 S, Raritan, NJ 08869, USA. Electronic address: [email protected].
¹¹ Janssen Research & Development, 700 US Highway 202 S, Raritan, NJ 08869, USA. Electronic address: [email protected].
¹² Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osakasayama, Osaka 589-8511, Japan. Electronic address: [email protected].
¹³ 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: [email protected].
¹⁴ BC Cancer and Vancouver Prostate Centre, 600 West 10th Avenue, Vancouver V5Z 1L3, British Columbia, Canada. Electronic address: [email protected].
¹⁵ Skåne University Hospital, Lund University, Jan Waldenströms gata 5, plan 2, 20502 Malmö, Sweden. Electronic address: [email protected].

PMID: 37708629
DOI: 10.1016/j.ejca.2023.113290

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Clinical trial registration: NCT02489318.

Keywords: High-volume; Low-volume; Metachronous; Oligometastatic; Polymetastatic; Synchronous; mCSPC.

Associated data

ClinicalTrials.gov/NCT02489318