LBA9 - TROPiCS-04, a randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (CT) in pretreated advanced urothelial carcinoma (aUC): Overall survival (OS) and safety analysis

Background

We report the final OS and safety analysis from the global, open-label, randomized phase 3 TROPiCS-04 study of SG in pretreated patients (pts) with aUC (NCT04527991).

Methods

Pts with aUC who received prior platinum (PT)-based CT and checkpoint inhibitor therapy were randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on days (D) 1 and 8 of 21-D cycles or treatment (tx) of physician’s choice (TPC; paclitaxel 175 mg/m² IV, docetaxel 75 mg/m² IV, or vinflunine 320 mg/m² IV, on D1 of 21-D cycles). The primary end point was OS.

Results

Overall, 711 pts were randomized (SG = 355, TPC = 356). Median age was 67 years and 182 (26%) pts had a Bellmunt risk score ≥ 2; 216 (30%) pts had ≥ 3 prior anticancer tx. After a median follow-up of 9.2 mo, the primary end point was not met (median OS with SG vs TPC, 10.3 vs 9.0 mo; hazard ratio [0.86; 95% confidence interval [CI], 0.73-1.02; 2-sided P = 0.087). Subgroup analyses of OS showed a consistent non-significant trend for most prespecified subgroups. The most frequent grade (G) ≥ 3 tx-related adverse events (TRAEs) with SG were neutropenia (35%; 12% being febrile neutropenia [FN]) and diarrhea (15%). G5 tx-emergent AEs were observed in 25 (7%) pts with SG and 7 (2%) pts with TPC. With SG, 16/25 G5 events were infections with neutropenia, occurring mostly in the first mo of tx in pts with ≥ 2 risk factors for FN. Primary prophylactic granulocyte colony stimulating factor (G-CSF) use was 21% with SG and 22% with TPC. Additional safety results are in Table.

Conclusions

SG did not show a significant improvement in OS vs TPC in pretreated aUC. Safety data were consistent with the known toxicity profile of SG across tumor types, except for increased rates of neutropenic complications in this high-risk population. These AEs may have impacted overall results and could possibly be mitigated by increasing use of primary G-CSF prophylaxis. Table: LBA9

Clinical trial identification

NCT04527991.

Editorial acknowledgement

Medical writing and editorial assistance were provided by Peggy Robinet, PharmD, PhD, of Parexel, and funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

P. Grivas: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Bristol Myers Squibb, Asieris Pharmaceuticals, Merck KGaA, Seattle Genetics, Aadi Bioscience, Pfizer, Janssen, Boston Gene, Genentech/Roche, Gilead Sciences, CG Oncology, ImmunityBio, Lucence Health, G1 Therapeutics, Fresenius Kabi, PureTech, Strata Oncology, Astellas Pharma, AbbVie; Financial Interests, Institutional, Local PI: Pfizer, Gilead Sciences, Bristol Myers Squibb, MSD, QED Therapeutics, GSK, Mirati Therapeutics, G1 Therapeutics, Merck KGaA, Acrivon Therapeutics, ALX Oncology, Genentech. 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. C. Vulsteke: Financial Interests, Personal, Advisory Board: MSD, Janssen-Cilag, GSK, Astellas Pharma, BMS, Leo Pharma, Bayer, AstraZeneca, Pfizer, Merck; Financial Interests, Institutional, Research Grant, Funding for research project on immune related toxicities: MSD. M. Gross Goupil: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Astellas, MSD, Ipsen, Eisai, Pfizer, Astellas; Financial Interests, Personal, Invited Speaker: BMS, Astellas, Amgen, MSD, Janssen, Eisai, BMS; Financial Interests, Personal, Invited Speaker, symposium during national congress: Merck, BMS; Financial Interests, Personal, Invited Speaker, slides on criteria of choice of treatment for kidney cancer - during a national meeting: Ipsen; Financial Interests, Personal, Invited Speaker, MSD standalone: MSD; Financial Interests, Personal, Invited Speaker, ArTUR congress -Ipsen symposium: Ipsen; Financial Interests, Personal, Invited Speaker, Avenir: Merck; Financial Interests, Personal, Advisory Board, EV-pembro / access: Astellas; Financial Interests, Personal, Advisory Board, EV-Pembro/ access: MSD; Financial Interests, Personal, Invited Speaker, ROUSO: Bayer; Financial Interests, Institutional, Coordinating PI: pfizer; Financial Interests, Institutional, Steering Committee Member, clinical trial: roche; Non-Financial Interests, Personal, Principal Investigator: Pfizer, Ipsen, Gilead, Roche, Bayer, Astellas, Janssen, BMS, MSD, AstraZeneca. 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De Santis: Financial Interests, Personal, Advisory Board, Advisory functions: Bioclin; Financial Interests, Personal, Advisory Board: AAA, Amgen, 4D, EISAI, Basilea, Merck/Serono, Bayer, BMS, Sanofi, Ipsen, Novartis/Sandoz, Immunomedics/Gilead, Roche, Ferring, SeaGen, Gilead; Financial Interests, Personal, Advisory Board, advisory function: Astellas, MSD; Financial Interests, Personal, Advisory Board, steering committee member: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board, Speaker fees: Pierre Fabre Oncology; Financial Interests, Personal, Steering Committee Member, advisory Board: AAA; Financial Interests, Personal, Steering Committee Member, advisory function: Amgen, Astellas, 4D; Financial Interests, Institutional, Coordinating PI, advisory function: AstraZeneca; Financial Interests, Institutional, Local PI, study fees: EISAI, Calithera, Immunomedics/Gilead, Ipsen, SeaGen, Gilead; Financial Interests, Institutional, Steering Committee Member, local PI: Basilea; Financial Interests, Personal, Local PI, advisory function: MSD; Financial Interests, Institutional, Steering Committee Member, honoraria: Merck/Serono, Bayer, BMS, Janssen; Financial Interests, Institutional, Local PI, trial fees: Nektar; Financial Interests, Personal, Steering Committee Member, honoraria: Sanofi, Roche/Genentech, Novartis, Sandoz, Ferring, Pierre Fabre; Non-Financial Interests, Personal, Member, writing and discussing guidelines for treatment and diagnostics: EAU Guidelines group prostate cancer; Non-Financial Interests, Personal, Member, Guidelines for bladder cancer treatment: S3 Leitlinie Blasenkrebs; Non-Financial Interests, Personal, Member, working on contents, text and review of publication: ESMO Clinical practice guidelines panel bladder cancer. 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Duran: Financial Interests, Personal, Advisory Board, I have served as an advisor for this company in the last two years: Roche Genentech, MSD, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by Janssen over the last two years: Janssen; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by Pfizer over the last two years: Pfizer; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor in different occasions over the last two years: Ipsen; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by this company over the last two years: Ipsen, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, I have participated in educational events sponsored by this company and I have received compensation for it: Merck; Financial Interests, Personal, Advisory Board, I have participated in different compensated advisory boards over the last two years: Astellas; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor for this company over the last two years: Immunomedics, Inc.; Financial Interests, Personal, Invited Speaker, I have participated in educational activities sponsored by this company in the last two years: Eusa Pharma, MSD; Financial Interests, Personal, Invited Speaker, I have participated in educational activities sponsored by Novartis in the last 2 years: Novartis; Financial Interests, Personal, Invited Speaker, I have participated in compensated educational activities for this company in the last two years: Astellas; Financial Interests, Personal, Invited Speaker, I have participated in activities sponsored by this company as a guest speaker: bayer; Financial Interests, Personal, Other, Bayer has covered expenses related to EAU 2023 including registration, travel and accommodation: Bayer; Financial Interests, Personal, Other, AstraZeneca has covered the cost of registration, accommodation and traveling related to my attendance of ASCO GU 2024: AstraZeneca; Financial Interests, Personal, Other, Merck has covered the cost related to my attendance to ASCO 2024. (Registration, travel and accommodation): Merck; Financial Interests, Personal and Institutional, Research Grant, Roche has funded research in my institution to projects under my coordination: Roche Genentech; Financial Interests, Personal, Steering Committee Member, I serve as a member of a SC for a trial sponsored by this company: Immunomedics, Inc.; Financial Interests, Personal and Institutional, Research Grant, AZ has funded research conducted in my institution related to a project where I am the PI: AstraZeneca; Financial Interests, Institutional, Coordinating PI, I am leading a study (Investigator initiated) that is funded by Gilead and sponsored by the foundation of my department (FUPOCAN). I am the national PI of this study and I don’t receive any compensation for this: Gilead; Non-Financial Interests, Personal, Leadership Role, I am the president of an independent cooperative group of GU Oncologist from the north of Spain: GO NORTE; Non-Financial Interests, Personal, Member of Board of Directors, I am member of the Board of directors since 2022: ASEICA; Non-Financial Interests, Personal, Member of Board of Directors, GUARD is a GU oncology cooperative group. I am a co-founder and member of the board of directors since 2023: GUARD; Non-Financial Interests, Personal, Member of Board of Directors, Grupo Germinal is the testicular cancer Spanish group, I am currently part of the board of directors since 2020 and future president of the group: GRUPO GERMINAL; Non-Financial Interests, Personal, Principal Investigator, I am the P.I. of the PRISMA-1 study for which FUPOCAN is the sponsor. This is a multicenter national investigator initiated trial in urothelial cancer running in 10 centres in Spain: FUPOCAN; Non-Financial Interests, Personal, Leadership Role, I am the CO-CHAIR of the GU-TRACK for ESMO ASIA 2024: ESMO; Non-Financial Interests, Personal, Other, I am a member of the International Development and Education Award (IDEA) Steering Group for ASCO: ASCO; Non-Financial Interests, Personal, Member, I am a member and co-founder of the Spanish patient advocacy group in bladder cancer CANVES. 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, Personal, Principal Investigator: AstraZeneca, Gilead, Roche, BMS, AstraZeneca, Pfizer, Astellas, MSD, Janssen, GSK, Loxo Oncology, TYRA. J. Guo: Financial Interests, Personal, Advisory Role: MSD, Roche, Pfizer, Bayer, Novartis, Simcere, Shanghai, Oriengeni. C.N. Sternberg: Financial Interests, Personal, Advisory Board, AD board and speaker at ESMO: Pfizer; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Astellas, Sanofi-Genzyme, Roche-Genentech, Foundation Medicine, Immunomedics, Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board, Was the head of the oversight committee, of Phase III trial but last meeting over 1 year ago: Seattle Genetics; Financial Interests, Personal, Advisory Board, less than $5000.00: Lilly; Financial Interests, Personal, Other, AD board: Bristol Myers Squibb; Financial Interests, Personal, Other, Speaker, owned by Prostate Cancer Foundation: Uro Today; Financial Interests, Personal, Other, Speaker, CME activities: Medscape. J. Bellmunt: Financial Interests, Personal, Advisory Board, Joined the Global adboard this year: Pfizer; Financial Interests, Personal, Advisory Board, Regular GU adboard for bladder cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures in the setting of National meetings: Merck; Financial Interests, Personal, Advisory Board, Bladder adboard: Merck; Financial Interests, Personal, Advisory Board, For the adjuvant study CM 247: BMS; Financial Interests, Personal, Invited Speaker, For ESMO Asia Symp 2020: MSD; Financial Interests, Personal, Stocks/Shares, Holdings: Bicycle; Financial Interests, Personal, Royalties, Role as Section Editor for Bladder: UpToDate; Financial Interests, Institutional, Coordinating PI, Pi of INDUCOMAIN Study (Avelumab first line in unfit patients) Though APRO Association: MSD; Financial Interests, Institutional, Coordinating PI, Pi of Prostate Study (Avelumab + Carboplatin) Though APRO Association: Pfizer; Non-Financial Interests, Personal, Other, Steering committee member of IMvigor 011: Genentech; Non-Financial Interests, Personal, Member: ASCO. P.J. Goebell: Financial Interests, Personal, Other, Travel expenses: Astellas Pharma, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Janssen, Novartis, Pfizer, Roche, Sanofi, EUSA Pharm; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Advisory Board, Honoraria: AstraZeneca, Bayer, BMS, Eisai, Ipsen, Janssen, Novartis, Pfizer, Roche, Sanofi, EUSA Pharma, MSD, Accord Healthcare, Recordati, Apogepha. F. Boateng: Financial Interests, Personal, Stocks/Shares, Employee stocks: Gilead Sciences. M. Sierecki, J. Waldes: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences Inc; Financial Interests, Personal, Stocks or ownership: Gilead Sciences Inc. L. Wang: Financial Interests, Personal, Full or part-time Employment: Gilead Science INC, Astellas Pharma US; Financial Interests, Personal, Stocks/Shares: Gilead Science INC. C. Sima: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences Inc, Roche; Financial Interests, Personal, Stocks or ownership: Gilead Sciences Inc, Roche; Financial Interests, Personal, Other, Travel: Gilead Sciences Inc, Roche. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: Ambrx, Telix Pharma, Blue Earth Diagnostics, Point Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity, Merck, EMD Serono, Regeneron, Daiichi Sankyo; Financial Interests, Personal, Other, DSMB: Boston Scientific; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Advisory Board, Patent: Convergent Therapeutics; Financial Interests, Personal, Advisory Board, Patent: Convergent Therapeutics; Financial Interests, Institutional, Local PI: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen; Financial Interests, Institutional, Steering Committee Member: Gilead, Novartis, Point Biopharma, Clarity, Ambrx, Promontory, Telix. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisory boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Personal, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Basilea, Tahio; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Personal, Member: ESMO, ASCO, AACR; Non-Financial Interests, Personal, Other, scientific committee: ARC. All other authors have declared no conflicts of interest.