Abstract 580P
Background
TALAPRO-1 enrolled men with progressive mCRPC and tumor DDRm involved either directly or indirectly in homologous recombination repair (HRR) (11-gene panel). These men had received 1–2 taxane-based chemotherapy and progressed on ≥1 novel hormonal therapy. The primary endpoint was objective response rate ([ORR] per RECIST v.1.1; central review). Exploratory ad hoc biomarker analyses assessed non-DDR/HRR mutational landscape and associations with antitumor activity.
Methods
Tumor alteration prevalence was assessed in the enrolled population evaluable for FoundationOne CDx® (n=123). Alterations were defined as known/likely pathogenic variants. Potential associations between alteration status of selected genes and antitumor activity were explored in the HRR-deficient measurable disease population evaluable for FoundationOne CDx® (n=100). Data cut-off was 4 Sept 2020.
Results
The most commonly altered non-HRR genes (prevalence ≥10%) were TMPRSS2, its fusion partner ERG, TP53, and PTEN when copy number alterations (CNAs) were excluded. The most common non-HRR CNAs (prevalence ≥9%) were PTEN, androgen receptor (AR), and MYC. Based on their importance in CRPC pathobiology and crosstalk potential with DDR/HRR pathways, associations between alteration status of TP53, PTEN, AR, or MYC and antitumor activity were explored. ORR was 30.0% (9/30) in men with TP53m and 28.6% (20/70) in men without TP53m (P = 1.00, 2-sided Fisher’s exact test). ORR was 34.5% (10/29) in men with PTENm and 26.8% (19/71) in men without PTENm (P = 0.47). ORR was independent of AR or MYC alteration status. There was no significant difference in radiographic PFS based on the alteration status of these 4 genes.
Conclusions
These results, coupled with the results of gene-agnostic visualizations of the FoundationOne CDx® gene panel as a function of response, demonstrate that in this population of men with mCRPC preselected on the basis of HRR alteration status, the alteration status of non-HRR genes does not appear to be associated with antitumor activity.
Clinical trial identification
NCT03148795.
Editorial acknowledgement
Medical writing support was provided by Michael Howell, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer.
Legal entity responsible for the study
Study sponsored by Pfizer.
Funding
This study was sponsored by Pfizer.
Disclosure
N. Mehra: Financial Interests, Personal, Other, Reports Consulting Fees: Astellas Pharma, Bristol-Myers Squibb, Genzyme, Janssen-Cilag, MSD Oncology, and Roche; Financial Interests, Institutional, Other, Funding or other support for research work to his institution: Astellas Pharma, Janssen-Cilag, Pfizer, Roche/Genentech, and Sanofi; Financial Interests, Personal, Other, Accommodation and expenses: Astellas Pharma, Bristol-Myers Squibb, MSD Oncology, and Roche. J. de Bono: Financial Interests, Personal, Other, Reports Consulting Fees: Astellas Pharma, AstraZeneca, Bayer, BioXcel Therapeutics, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eisai, Genmab, GSK, Janssen Oncology, Menarini Silicon Biosystems, Merck Serono, MSD, Orion Pharma GmbH, Pfizer, Roche/Genentech, Sanofi, Sierra Onco; Financial Interests, Institutional, Funding, Funding or other support for research work to his institution: Astex Pharmaceuticals, AstraZeneca, Bayer, Celgene, Cellcentric, Daiichi Sankyo, Genentech, GSK, MedImmune, Medivation, Merck Serono, MSD, Orion Pharma GmbH, Sanofi, Sierra Oncology, and Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, AstraZeneca, BioXcel Therapeutics, Daiichi Sankyo, Janssen Oncology, Menarini Silicon Biosystems, Pfizer, Roche/Genentech, Sanofi, and Sierra Oncology; Financial Interests, Invited Speaker, Travel, accommodation, and expenses: Astellas Pharma, AstraZeneca, Genmab, GSK, Qiagen, Orion Pharma GmbH, Sanofi, Taiho Pharmaceutical, and Vertex; Non-Financial Interests, Personal, Other, Inventor: Inventor for patent 8,822,438. A.D. Laird: Financial Interests, Personal, Full or part-time Employment, Stocks/Stock options: Pfizer. P. Barthélémy: Financial Interests, Personal, Other, Reports advisory/consultancy fees: Amgen, Astellas, Bristol-Myers Squibb, Cilag, EUSA Pharma, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi; Financial Interests, Personal, Other, Travel expenses, including accommodations: Astellas, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Pfizer, Roche, and Sanofi; Financial Interests, Personal, Other, Travel/accommodations/expenses: Bristol-Myers Squibb, Ipsen, Janssen, MSD, Pfizer, and Roche. T. Dorff: Financial Interests, Personal, Other, Reports consulting: Advanced Accelerator Applications, Bayer, Bristol-Myers Squibb, Dendreon, Janssen, and Seattle Genetics. A. Stirling: Financial Interests, Personal, Other, reports honoraria: AstraZeneca and Pfizer. J. Machiels: Financial Interests, Personal, Other, Reports personal financial interests: ALX Oncology, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cue Biopharma, Debio, Incyte, Innate, Janssen, Johnson & Johnson, Merck-Serono, MSD, Nanobiotix, Novartis, Pfizer, and Roche; Financial Interests, Institutional, Other, Institutional financial interests: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Celyad, GlaxoSmithKline, Incyte, iTeos, Janssen, Johnson & Johnson, KURA, Lilly, Merck-Serono, MSD, Novartis, Pfizer, Roche, and Sanofi-Aventis; Non-Financial Interests, Personal, Other, Nonfinancial interests: AstraZeneca Steering Committee for head and neck trial (Kestrel) and MSD Steering Committee for head and neck cancer trial (412); Financial Interests, Personal, Other, Travel expenses: Amgen, Bristol-Myers Squibb, MSD, and Pfizer; Other, Personal, Member of the Board of Directors: Belgian Society of Medical Oncology; Other, Personal, Member: Belgian Foundation Against Cancer; Other, Personal, Member: EORTC and active investigator/study coordinator of the EORTC 1559 trial. H. Dumez: Financial Interests, Personal, Other, received travel/meeting accommodations: Astellas, AstraZeneca, Bayer, Ipsen, Janssen-Cilag, MSD, Novartis, Pfizer, Roche, and Sanofi. V. Renard: Financial Interests, Personal, Other, Travel and accommodation expenses: AstraZeneca, Ipsen and Pfizer; Financial Interests, Personal, Other, Accommodation expenses: Novartis. J. Hopkins: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine Inc; Financial Interests, Personal, Other, Stockholder: Roche Holding AG. L.A. Albacker: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine Inc; Financial Interests, Personal, Other, Stockholder: Roche Holding AG. H. Chen: Financial Interests, Personal, Full or part-time Employment, Stocks/Stock options: Pfizer. C. Healy: Financial Interests, Personal, Full or part-time Employment, Holds Pfizer stock/stock options: Pfizer. J. Chelliserry: Financial Interests, Personal, Full or part-time Employment, holds Pfizer stock/stock options: Pfizer. I.M. van Oort: Financial Interests, Personal, Other, Reports Consulting Fees: Astellas Pharma, Bayer, Ipsen, Janssen, Roche, and Sanofi; Financial Interests, Personal, Funding, Research funding: Astellas Pharma and Bayer. G. Scagliotti: Financial Interests, Personal, Other, Reports commercial interest, relationship(s) and honoraria: AstraZeneca, Eli Lilly, Johnson & Johnson, MSD, Pfizer, Roche, and Takeda; Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, Beigene, and Eli Lilly; Financial Interests, Institutional, Other, Institutional Grants: Eli Lilly, MSD and Tesaro and Travel; Financial Interests, Personal, Other, Accommodation Bayer. K. Fizazi: Financial Interests, Personal, Other, Reports Consulting Fees: Astellas Pharma, Bayer, Clovis, CureVac, ESSA, Janssen Oncology, Orion Pharma GmbH, and Sanofi; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Bayer, Janssen, and Sanofi; Financial Interests, Personal, Other, Travel, accommodation, and expenses: Amgen, Janssen, and MSD. All other authors have declared no conflicts of interest.