Post hoc analysis of outcomes according to prior chemotherapy (CT) response and platinum agent in the international SAUL study of atezolizumab (atezo) for urinary tract carcinoma (UTC)

BackgroundThe single-arm SAUL study (NCT02928406) enrolled a broad population of patients (pts) in a real-world setting, including pts with comorbidities. Median overall survival (OS) with atezo was 8.6 months, similar to results in more selected clinical trial populations. We explored whether response to previous CT and type of platinum influenced outcomes in atezo-treated pts.MethodsSAUL enrolled pts with platinum-pretreated locally advanced/metastatic urothelial or non-urothelial UTC. Broad eligibility criteria were designed to allow enrolment of pts from understudied populations approximating the real-world setting. Pts received atezo until disease progression (PD) or unacceptable toxicity. In post hoc analyses, efficacy (objective response rate, duration of response [DoR], OS) was assessed according to investigator-reported response to prior CT and type of CT (cisplatin vs other platinum).ResultsIn 1004 enrolled pts, 60% had previously received cisplatin, 38% received carboplatin without cisplatin and 2% received non-platinum agents (predominantly gemcitabine). Overall, 33% had a complete or partial response (CR/PR) to prior CT and 20% had stable disease (SD). The best outcomes on atezo were seen in pts with CR to prior CT and in cisplatin-pretreated pts. However, 36% of pts with PD as best response to prior CT had CR/PR/SD on atezo and a subset (mainly with ECOG performance status 0/1 and few comorbidities) showed remarkable outcomes (CR in 3%, median DoR >2 years, OS >4 years in 15%), irrespective of PD-L1 status (Table). Table: 1982P Subgroup Outcome on atezo Best objective response, n (%) Median DoR, mo (95% CI) OS (95% CI) CR PR SD PD Median, mo 4-year rate, % Best response to prior CT CR (n=80) 14 (18) 13 (16) 20 (25) 23 (29) 48.1 (13.2–NE) 23.3 (13.5–37.4) 31 (20–42) PR (n=248) 10 (4) 19 (8) 60 (24) 104 (42) 27.3 (11.8–NE) 9.1 (7.3–10.7) 16 (12–21) SD (n=202) 6 (3) 28 (14) 53 (26) 77 (38) 32.5 (11.1–45.5) 10.1 (8.0–12.0) 17 (11–22) PD (n=320) 10 (3) 32 (10) 73 (23) 135 (42) 25.6 (11.7–NE) 6.5 (5.4–7.9) 15 (11–19) Prior platinum Cisplatin (n=599) 35 (6) 66 (11) 140 (23) 239 (40) 35.2 (18.9–52.8) 9.2 (8.0–10.6) 19 (16–23) Non-cisplatina (n=380) 12 (3) 39 (10) 98 (26) 144 (38) 21.8 (11.0–41.9) 7.4 (6.3–8.8) 14 (10–18) a377 carboplatin, 3 oxaliplatin. NE = not estimable. ConclusionsAtezo demonstrated activity irrespective of sensitivity to prior CT and prior platinum agent. A subset of pts with PD during prior CT (but fit enough for further therapy) experienced sustained clinical benefit from atezo.Clinical trial identificationEudraCT 2016-002625-11.Editorial acknowledgementJennifer Kelly (Medi-Kelsey Ltd).Legal entity responsible for the studyF. Hoffmann-La Roche Ltd.FundingF. Hoffmann-La Roche Ltd.DisclosureB. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, Bristol Myers Squibb, Ipsen, EUSA Pharma, Merck, MSD, Astra-Zeneca, AAA, Recordati; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Bayer, MSD, Merck, Pfizer, Astellas Pharma, AAA, Almirall pharma; Other, Travel/accommodations: Bristol Myers Squibb, Pfizer. X. Garcia Del Muro: Financial Interests, Personal, Advisory Board: Ipsen, BMS, Pfizer, Roche, PharmaMar, GSK, Merck, Deciphera, MSD; Financial Interests, Personal, Invited Speaker: Lilly, Astellas Pharma, Eisai, Pfizer, Recordati; Financial Interests, Institutional, Research Grant: AZ, Incyte. A.S. Merseburger: Financial Interests, Personal, Advisory Board, Speaker: Janssen; Financial Interests, Personal, Advisory Board, Speaker, Advisor: Astellas; Financial Interests, Personal, Advisory Board, Advisor: Bayer, Seagen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Member of Board of Directors, Travel costs: EAU. 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, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Steering Committee Member: Basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelixis, Astra Zeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, scientific committee: ARC. E. Choy: Financial Interests, Personal, Advisory Board: AbbVie, Biocon, Biogen, Janssen, Sanofi, USB; Financial Interests, Personal, Invited Speaker: Eli Lilly, Galapagos, Janssen, Sanofi, Viatris; Financial Interests, Personal, Stocks/Shares: Inmedix; Financial Interests, Institutional, Research Grant: Pfizer, Sanofi, Biocancer; Financial Interests, Personal and Institutional, Steering Committee Member: Roche. D.E. Castellano Gauna: Financial Interests, Personal, Advisory Board: Pfizer, Roche, BMS, Janssen, Astellas, MSD, Ipsen, AstraZeneca, Novartis, GSK; Financial Interests, Institutional, Local PI: Pfizer, Roche, MSD, BMS, AstraZeneca, Janssen, Astellas, Ipsen, Exelisis, Eisai, Lilly, Bayer, GSK, Clovis, QED Therapeutics; Non-Financial Interests, Other, any: Associate Professor of Medical Oncology/Internal Medicine department; Non-Financial Interests, Personal, Other, Executive member: SOGUG (Spanish Oncology Genito-Urinary Group) Foundation; Non-Financial Interests, Personal, Training, Head of GU Alliance for Research and Development Consortium: GUARD Consortium; Other, any: Member of the Internal/local Pharmacy Commission at the Hospital Universitario 12 de Octubre. F. Lopez-Rios: Financial Interests, Personal, Advisory Board: Roche, Janssen, MSD, AZ, Bayer, BMS, Takeda, Thermo Fisher, Lilly, Pfizer, AbbVie, DS; Financial Interests, Personal, Invited Speaker: Roche, Lilly, Janssen, MSD, AZ, Pfizer, Bayer, BMS, Takeda, Thermo Fisher; Financial Interests, Institutional, Research Grant: Thermo Fisher, Lilly, Roche, Pfizer, AZ. P. Yu: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: Roche. P. Skamnioti: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: Roche. 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 if 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. All other authors have declared no conflicts of interest.