Abstract 1370P
Background
In PROpel (NCT03732820), pts were enrolled irrespective of HRR gene mutation (HRRm) status. However, determination of HRRm and evaluation of radiographic progression-free survival by HRRm status were predefined endpoints. TT testing is considered the reference for assessment of HRRm but, given potential challenges in obtaining sufficient quantity of quality TT, ctDNA testing was also conducted.
Methods
Archival TT and blood samples were collected at baseline from >98% of randomised pts and analysed by the FoundationOne®CDx and FoundationOneLiquid®CDx molecular diagnostic tests, respectively. HRRm status (HRRm, non-HRRm or HRRm unknown) was assigned by individual test result and using an aggregate of the results from both tests. For aggregate results, pts were classified as HRRm if an HRRm was detected by either test; non-HRRm if no HRRm was detected by either test; or HRRm unknown if they did not have a valid HRRm test result.
Results
Of the 796 pts randomized, 782 had TT samples and 794 had blood samples available for testing. Of the pts with TT samples, 535 (68%) were successfully assessed for HRRm status by TT test, while 734 (92%) of pts with blood samples were successfully assessed by ctDNA test. Aggregate HRRm status was obtained for 778 (98%) pts (226 HRRm, 552 non-HRRm and 18 HRRm unknown). Using TT as a reference, positive-percent agreement was 80%, negative-percent agreement was 87%, overall-percent agreement was 85% and the positive and negative predictive values were 64% and 94%, respectively. In the HRRm by ctDNA subgroup 51 pts were non-HRRm by TT. The negative predictive value suggests that in the non-HRRm by ctDNA subgroup ∼174/186 (94%) pts would also be non-HRRm by TT test. Therefore, there were ∼12 potential false negative results by ctDNA test in the total non-HRRm aggregate population (2% of 552 pts).
Conclusions
There was good agreement between matched TT and ctDNA test results in PROpel. Using aggregate test results, it was possible to maximize the number of pts with known HRRm status while controlling the number of potential false negative results, thus facilitating robust analysis of HRRm status.
Clinical trial identification
NCT03732820.
Editorial acknowledgement
Medical writing support was provided by Laura Smart, MChem, at Mudskipper Business Ltd., funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
A.J. Armstrong: Financial Interests, Personal, Advisory Role: Janssen; Novartis; Myovant Sciences; Bayer; Exelixis; Dendreon; Merck; GoodRx; AstraZeneca; FORMA Therapeutics; Astellas Scientific and Medical Affairs Inc.; Pfizer; Bristol Myers Squibb; Exelixis; Financial Interests, Institutional, Funding: Gilead Sciences (Inst); Roche/Genentech (Inst); Bristol Myers Squibb (Inst); AstraZeneca (Inst); FORMA Therapeutics (Inst); Astellas Pharma (Inst); Constellation Pharmaceuticals (Inst); Dendreon (Inst); Pfizer (Inst); Amgen (Inst); Novartis (Inst); Jansse; Financial Interests, Institutional, Royalties: Circulating tumor cell novel capture technology (Inst); Financial Interests, Personal, Other, Travel/accommodation: Astellas Scientific and Medical Affairs Inc. F. Saad: Financial Interests, Personal, Other, Honoraria: AbbVie; Advanced Accelerator Applications; Astellas Pharma; AstraZeneca; Bayer; BMS; Janssen Oncology; Knight Therapeutics; Merck; Myovant Sciences; Novartis; Pfizer; Sanofi; Financial Interests, Personal, Advisory Role: AbbVie; Advanced Accelerator Applications; Astellas Pharma; AstraZeneca/MedImmune; Bayer; Janssen Oncology; Knight Therapeutics; Myovant Sciences; Novartis; Pfizer; Sanofi; Financial Interests, Institutional, Funding: Advanced Accelerator Applications (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bayer (Inst); Bristol Myers Squibb (Inst); Janssen Oncology (Inst); Merck (Inst); Novartis (Inst); Pfizer (Inst); Sanofi (Inst). A. Thiery-Vuillemin: Financial Interests, Personal, Other, Honoraria: Pfizer; AstraZeneca; Sanofi; Janssen; Novartis; Ipsen; Roche/Genentech; Bristol Myers Squibb; MSD; Astellas Pharma; Financial Interests, Personal, Advisory Role: Pfizer; AstraZeneca; Sanofi; Janssen; Novartis; Ipsen; Roche; Bristol Myers Squibb; MSD; Astellas Pharma; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Other, Travel/accommodation: Roche; MSD; Janssen; Bristol Myers Squibb; AstraZeneca; Pfizer; Astellas Pharma; Ipsen. M. Oya: Financial Interests, Personal, Other, Honoraria: Bayer; Bristol Myers Squibb; Novartis; Ono Pharmaceutical; Pfizer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Funding: Novartis; Pfizer. N.D. Shore: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Dendreon, Ferring, Janssen, Merck, MDxHealth, Pfizer, Sanofi, Tolmar. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Invited Speaker: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, Co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry. M. Ozguroglu: Financial Interests, Personal, Funding: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Institutional, Funding: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Travel/Accommodation: BMS, Janssen, AstraZeneca. C. Gedye: Financial Interests, Institutional, Speaker’s Bureau: BMS, MSD, AZ, Iosen, Pfizer, AbbVie, Astellas, Amge; Financial Interests, Personal, Other, Travel support: BMS, MSD, Astellas; Financial Interests, Institutional, Other: MSD, BMS, Amgen. O. Sartor: Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications (AAA), Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Inc., Bavarian Nordic, Bristol Myers Squibb, Clarity Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, Fusion, Isotopen Technologien Meunchen, Janss; Financial Interests, Personal, Funding: Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Constellation, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, Tenebio. C.H. Poehlein: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. P. Qiu: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. Y. Liu, L. Riva, L. Harrington, L. Barker, P.M.D. Del Rosario, A. Barnicle: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Clarke: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Janssen; Bayer; AstraZeneca.