Abstract 1970MO
Background
The VOLGA safety run-in (SRI) of neoadjuvant D + T + EV in cisplatin-ineligible patients (pts) with MIBC showed promising results (NCT04960709). Here, an exploratory analysis of plasma ctDNA from the SRI is presented.
Methods
Eligible pts were ≥18 years with cisplatin-ineligible MIBC (clinical stage T2-4aN0-N1M0/T1N1M0). Pts received 3 cycles of neoadjuvant therapy Q3W: D (1500 mg; day 1 each cycle) + T (75 mg; day 1 cycle 1, and day 8 cycle 2) + EV (1.25 mg/kg; days 1 and 8 each cycle), followed by radical cystectomy (RC), then 9 cycles of adjuvant D (Q4W; day 1 each cycle) and T (day 1, cycle 1 only). Cell-free DNA from plasma samples was assessed using GRAIL’s cancer research solution, which detects methylation indicative of ctDNA (GRAIL, LLC). ctDNA detection at baseline (C1D1) and on/after neoadjuvant treatment prior to RC (C3D1 and pre-RC time points) was evaluated for association with pathologic response at RC and event-free survival (EFS).
Results
Of 69 plasma samples across baseline, pre-RC, and post-RC time points, 66 (96%) passed a ctDNA processing quality control check. Of the 17 pts in the SRI cohort, 16 had baseline plasma samples with a ctDNA-positive rate of 62.5% (10/16 pts). Of these, 13 underwent RC and had a pre-RC sample. The ctDNA-positive rate at C3D1/pre-RC was 23% (3/13 pts); 7 pts had ctDNA clearance, which was associated with pathologic response (table) and EFS (EFS hazard ratio 0.18 [95% CI, 0.016-2.1]). ctDNA detection status alone at C3D1/pre-RC was also associated with pathologic response (table). Table: 1970MO
| Pathologic assessment at RC (n=14)a | Baseline ctDNA positive, n | Baseline ctDNA negative, n | C3D1/pre-RC ctDNA positive, n | C3D1/pre-RC ctDNA negative, n | ctDNA clearance on D + T + EV, n |
| pCR (n=6) | 5 | 1 | 0 | 6 | 5 |
Downstaged toConclusionsThis exploratory analysis of the VOLGA SRI cohort showed that plasma ctDNA clearance during neoadjuvant D + T + EV treatment of MIBC pts may be associated with improved clinical outcomes, making it a potential surrogate for treatment efficacy. These findings will be further explored in the ongoing VOLGA study. Funding: AstraZeneca. Clinical trial identificationNCT04960709; July 14, 2021. Editorial acknowledgementEditorial and medical writing support was provided by Lewis Cawkwell, PhD, of Parexel, and was funded by AstraZeneca. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureA. Drakaki: Non-Financial Interests, Advisory Board: AstraZeneca, Merck, Exelixis, EMD Serono, AVEO, Seagen, Eli Lilly, Silverback Therapeutics, Roche, Genentech, Infinity, Presisca, Nektar Therapeutics; Other, Leadership Role, Educational Board: ASCO; Other, Leadership Role, committee meeting chair: SITC. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Other, honoraria: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Other, Honoraria: Gilead. Y. Wang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Bupathi: Financial Interests, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis; Financial Interests, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Exelixis, Pfizer, Astellas Pharma, Janssen Oncology; Financial Interests, Other, Honoraria: Bristol Myers Squibb, Exelixis, Bayer, Mayovant Sciences, Janssen. M. Joshi: Non-Financial Interests, Coordinating PI: AstraZeneca. M.T. Fleming: Financial Interests, Advisory Board: Janssen Oncology, Dendreon; Non-Financial Interests, Other, Leadership: US Oncology; Financial Interests, Speaker’s Bureau: GenenTech, Janssen Oncology; Other, travel, accommodation, expenses: Medivation/Astellas, GenenTech; Financial Interests, Full or part-time Employment: Virginia Oncology Associates. A. Gomez de Liano Lista: Financial Interests, Speaker, Consultant, Advisor: Astellas, BMS, Ipsen, Janssen, Merck, MSD, Roche; Financial Interests, Speaker’s Bureau: Astellas, BMS, Ipsen, Merck, MSD, Roche; Other, Meetings and/or travel: Astellas, BMS, Ipsen, Janssen, Merck, MSD, Roche; Non-Financial Interests, Leadership Role, Scientific Committee: GUARD consortium; Non-Financial Interests, Member of Board of Directors: Grupo Germinal. R. Morales Barrera: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer, Astellas, Merck; Financial Interests, Personal, Other, Congress registration/travel/accommodation: Bayer; Financial Interests, Personal, Other, Congress registration: BMS; Financial Interests, Institutional, Other, Institutional: AB Science, Aragon Pharmaceuticals, Bayer, Aveo Pharmaceuticals INC, Astellas, AstraZeneca, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim, Clovis Oncology, Deciphera Pharmaceuticals LLC, Exelixis, Roche, Genentech, GSK, Incyte Corporation, Karyopharm Therapeutics INC, Laboratoires Leurquin Mediolanum, Lilly, Medimmune, Millennium Pharmaceuticals, Nanobiotix, Novartis, Pfizer, Sanofi-Aventis, SFJ Pharma LTD, Teva Pharma; Financial Interests, Personal, Other, Congress registration, accommodation/travel: Merck; Non-Financial Interests, Principal Investigator: AstraZeneca, Gilead, Roche, BMS, AstraZeneca, Pfizer, Astellas, MSD, Janssen, GSK, Loxo Oncology, Tyra. R. Pili: Financial Interests, Personal, Advisory Board: Allarity; Financial Interests, Institutional, Research Grant: Genentech. S. Boulos, Y. Shrestha: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. 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