Abstract 581P
Background
In TALAPRO-1, TALA showed promising antitumor activity and manageable toxicity. A secondary objective was change from baseline in pt reported pain, measured by the Brief Pain Inventory-Short Form (BPI-SF).
Methods
In this 1-arm phase II study, men with mCRPC and DNA Damage Repair alteration (DDRm) either directly or indirectly involved in homologous recombination repair (HRR) who had previously received taxane-based chemotherapy (CT) and progressed on ≥1 novel hormonal agent (NHT) (abiraterone and/or enzalutamide) received TALA (1mg/d). Pts completed the BPI-SF at baseline, every (q) 2 wks until wk 9, q4 wks until wk 25 and q12 wks until disease progression. A longitudinal mixed effects model estimated the mean overall change from baseline for pain burden (worst, severity, and interference). Kaplan-Meier method estimated time to deterioration (TTD) for worst pain, pain severity and time to 1st opioid use. TTD was defined as ≥ 2-point increase from baseline for 2 consecutive visits at least 4 wks apart without a decrease in WHO analgesic usage score.
Results
97 pts with a baseline and ≥ 1 post baseline assessment were included; 56 pts had BRCA1/2 alterations. Improvements in the overall change from baseline in pain burden were observed in both groups (Table). In the TTD analysis for worst pain, 84.0% of the all pt group and 82.9% of the BRCA1/2 subset had not deteriorated by month 12. In the TTD analysis for pain severity, 89.2% of the all pt group and 89.1% of the BRCA1/2 subset had not deteriorated by month 12. The probability of remaining opioid free at 12-months was 56.6% for the all pt group and 56.7% for the BRCA1/2 subset. Table: 581P
BPI-SF Estimated Overall Change from Baseline Scores (95% CI)*
| All pts N=97 | BRCA1/2 subset N=56 | |
| Worst pain | -1.08 (-1.52, -0.65) | -1.15 (-1.67, -0.62) |
| Severity | -0.67 (-0.99, -0.34) | -0.74 (-1.15, -0.32) |
| Interference | -0.74 (-1.12, -0.36) | -1.09 (-1.53, -0.66) |
| General activity | -0.96 (-1.38, -0.53) | -1.11 (-1.61, -0.61) |
| Mood | -0.57, (-0.94, -0.20) | -0.95 (-1.37, -0.53) |
| Walking ability | -0.86 (-1.29, -0.42) | -1.34 (-1.82, -0.87) |
| Normal walk | -0.92 (-1.42, -0.43) | -1.30 (-1.88, -0.71) |
| Relations | -0.17 (-0.57, 0.22) | -0.58, (-1.01, -0.16) |
| Sleep | -0.94 (-1.31, -0.58) | -1.20 (-1.60, -0.80) |
| Enjoyment of life | -0.91 (-1.36, -0.46) | -1.27 (-1.82, -0.72) |
*95% CI’s with negative lower and upper limits indicate improvements are significantly greater than zero.
Conclusions
TALA improved pain burden in men with mCRPC harboring HRR/DDRalt pretreated with taxanes and NHT. These findings, combined with the antitumor activity and tolerability, depict a favorable benefit-risk profile.
Clinical trial identification
NCT03148795.
Editorial acknowledgement
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
F. Saad: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Myovant. J.S. de Bono: Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Cellcentric; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Genentech Roche; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Harpoon; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Orion Pharma; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Sanofi Aventis; Financial Interests, Institutional, Research Grant: Sierra Oncology; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Vertex Pharmaceuticals; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bioxcel Therapeutics; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Cellcentric; Financial Interests, Personal, Advisory Role: Daiichi; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Genentech Roche; Financial Interests, Personal, Advisory Role: Genmab; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Harpoon; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Menarini Silicon Biosystems; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Orion Pharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Qiagen; Financial Interests, Personal, Advisory Role: Sanofi Aventis; Financial Interests, Personal, Advisory Role: Sierra Oncology; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: Terumo; Financial Interests, Personal, Advisory Role: Vertex Pharmaceuticals. P. Barthelemy: Financial Interests, Personal, Other, Honoraria: SEAGEN; Financial Interests, Personal, Advisory Role: Cilag; Financial Interests, Personal, Advisory Role: EUSA Pharma; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Janssen. T. Dorff: Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: SeaGen; Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications; Financial Interests, Personal, Advisory Board: BMS. N. Mehra: Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: Prevents; Financial Interests, Personal, Speaker’s Bureau: MedTalks. G. Scagliotti: Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Clovis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Beigene. A. Stirling: Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca. V. Renard: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis. C. Healy: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. H. Bhattacharyya: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. B. Arondekar: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. A. Niyazov: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. K. Fizazi: Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Janssen Research & Development; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Janssen Research & Development; Financial Interests, Personal, Advisory Role: Orion Pharma GmbH. All other authors have declared no conflicts of interest.