Abstract 608P
Background
In TITAN study, the addition of APA to androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) for mCSPC patients (Chi, NEJM, 2019; Chi et al, J Clin Oncol 39(6_suppl): 11, 2021). As there can be regional differences in outcomes, this TITAN Asian subgroup analysis was conducted.
Methods
This was a post-hoc analysis of subjects recruited from Japan, China and South Korea. TITAN was a phase III randomised, double blinded study. mCSPC patients were assigned (1:1) to receive either APA (240mg daily) or placebo (PBO), in addition to ADT. The co-primary end points were rPFS and OS. Exploratory end points included time to castration resistance (TTCR) and time to PSA progression (TTPP).
Results
This subgroup analysis included 111 patients on APA and 110 patients on PBO group (median age 70 years). After the first analysis, 42.7% of patients in the PBO group crossed over to receive APA. In the final analysis of rPFS, APA group had a statistically significant longer rPFS compared to PBO group (Hazard ratio (HR) 0.511, 95% CI 0.305, 0.856; p=0.0094). In the final analysis of OS with a median follow-up duration of 42.5 months, there was a trend for improved OS in the APA group compared to PBO (HR 0.685, 95% CI 0.416,1.126; p=0.1335) that was consistent with the overall population (Table). TTCR and TTPP were significantly improved in APA versus PBO group (HR 0.309, 95% CI 0.206, 0.463; p<0.001); HR 0.213, 95% CI 0.131, 0.346; p<0.001, respectively). Frequency of treatment-emergent adverse events (TEAEs) was 96.4% with APA and 98.2% with PBO treatment. Skin rash incidence during apalutamide treatment (43.6%) was higher than on PBO (10.9%). Table: 608P
Key clinical findings
| Clinical outcomes | Asian cohort final analysis, APA VS PBO | P value | Global overall cohortfinal analysis, APA VS PBO | P value |
| OS (median) | NE vs NE, HR 0.685 | 0.1335 | NE vs 52.2 months, HR 0.65 | <0.0001 |
| rPFS (median)∗ | NE vs NE, HR 0.511 | 0.0094 | NE vs 22.1 months, HR 0.48 | <0.001 |
| Time to castration resistance (median) | NE vs 12.1 months, HR 0.309 | <0.001 | NE vs 11.4 months, HR 0.34 | <0.0001 |
| Time to PSA progression (median) | NE vs 12.91 months, HR 0.213 | <0.001 | NE vs 12.9 months, HR 0.27 | <0.0001 |
∗ From apalutamide phase III TITAN study interim analysis 1.
Conclusions
In this TITAN Asian subgroup analysis, efficacy and safety of APA were consistent with the overall global cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Johnson & Johnson Ptd. Ltd.
Funding
Janssen, pharmaceutical company of Johnson & Johnson Ptd. Ltd.
Disclosure
B.H. Chung: Non-Financial Interests, Institutional, Advisory Board: Janssen Korea; Non-Financial Interests, Institutional, Advisory Board: Astellas Korea; Non-Financial Interests, Institutional, Advisory Board: JW pharma Korea; Non-Financial Interests, Institutional, Advisory Board: Handok pharma Korea; Non-Financial Interests, Institutional, Advisory Board: Ipsen Korea; Non-Financial Interests, Institutional, Advisory Board: DK Pharma Korea; Non-Financial Interests, Institutional, Advisory Board: Takeda Korea; Non-Financial Interests, Institutional, Advisory Board: Hanall Pharma Korea; Non-Financial Interests, Institutional, Advisory Board: Amgen Korea. S.D. Brookman-May: Non-Financial Interests, Personal, Full or part-time Employment: Janssen, pharmaceutical company of Johnson & Johnson. S. McCarthy: Non-Financial Interests, Personal, Full or part-time Employment: Janssen, pharmaceutical company of Johnson & Johnson. A. Bhaumik: Non-Financial Interests, Personal, Full or part-time Employment: Janssen, pharmaceutical company of Johnson & Johnson. J. He: Non-Financial Interests, Personal, Full or part-time Employment: Janssen, pharmaceutical company of Johnson & Johnson. S.D. Mundle: Non-Financial Interests, Personal, Full or part-time Employment: Janssen, pharmaceutical company of Johnson & Johnson. N. Agarwal: Financial Interests, Personal, Advisory Role, Consultancy: Astellas; Financial Interests, Personal, Advisory Role, Consultancy: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy: Aveo; Financial Interests, Personal, Advisory Role, Consultancy: Bayer; Financial Interests, Personal, Advisory Role, Consultancy: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consultancy: Calithera; Financial Interests, Personal, Advisory Role, Consultancy: Clovis; Financial Interests, Personal, Advisory Role, Consultancy: Eisai; Financial Interests, Personal, Advisory Role, Consultancy: Eli Lilly; Financial Interests, Personal, Advisory Role, Consultancy: EMD Serono; Financial Interests, Personal, Advisory Role, Consultancy: Exelixis; Financial Interests, Personal, Advisory Role, Consultancy: Foundation Medicine; Financial Interests, Personal, Advisory Role, Consultancy: Genentech; Financial Interests, Personal, Advisory Role, Consultancy: Gilead; Financial Interests, Personal, Advisory Role, Consultancy: Merck; Financial Interests, Personal, Advisory Role, Consultancy: MEI Pharma; Financial Interests, Personal, Advisory Role, Consultancy: Nektar; Financial Interests, Personal, Advisory Role, Consultancy: Novartis; Financial Interests, Personal, Advisory Role, Consultancy: Pfizer; Financial Interests, Personal, Advisory Role, Consultancy: Pharmacyclics; Financial Interests, Personal, Advisory Role, Consultancy: Seattle Genetics. K.N. Chi: Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: AstraZeneca; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Bayer; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Astellas; Financial Interests, Personal, Advisory Role, Personal fees for consulting: Daiichi Sankyo; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Novartis; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Pfizer; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Point Biopharma; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Roche; Financial Interests, Personal, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Sanofi; Financial Interests, Personal, Advisory Role, Personal fees for consulting: Merck; Financial Interests, Personal, Advisory Role, Personal fees for consulting: Bristol-Myers Squibb. H. Uemura: Financial Interests, Personal, Advisory Role: Bayer, MSD, Janssen, Sanofi, BMS; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Ono pharm, Daiichisankyo, Astelas, Janssen, MSD, Sanofi, Takeda, Chugai; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Bayer, Tsiho, Astelas, Janssen, MSD, Takeda, Chugai, BMS, Ono pharm; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, BMS, Ono pharm, Janssen, MSD, Sanofi, Chugai. All other authors have declared no conflicts of interest.