Abstract 1739P
Background
We hypothesise that the addition of pembrolizumab (pembro) may be safe and improve efficacy in patients (pts) with MIBC treated with chemoradiotherapy (CRT).
Methods
This multicentre phase 2 trial included pts with non-metastatic cT2-T4aN0M0 MIBC (>50% TCC histology) who declined cystectomy or for whom cystectomy was unsuitable, with no contraindications to CRT or pembro, ECOG performance status 0 or 1, eGFR ≥40 mL/min. Neoadjuvant chemotherapy was not permitted. Pts had maximal TURBT, then whole bladder radiation therapy (RT) (64Gy in 32 daily fractions, mostly IMRT) over 6.5 weeks with weekly cisplatin (35 mg/m2 IV, 6 doses) and pembro 200mg IV q3 wks x 7 doses, both starting with RT. Surveillance cystoscopy, urine cytology, and CT chest-abdomen-pelvis were performed 12 & 24 weeks after CRT. The primary endpoint was feasibility, determined by a prespecified satisfactory low rate of grade 3-4 non-urinary toxicity, or completion of planned CRT according to defined parameters (RT < 7 weeks, >1 cisplatin dose omission). Secondary endpoints include complete cystoscopic response without metastatic disease at 12 & 24 weeks, loco-regional PFS, metastatic DFS, and OS.
Results
From 2016 – 2021 27 pts (93% male, median age 71, 96% pure TCC, 34% with CIS, 93% pT2) were enrolled at 6 sites. Median follow up at April 2022 was 31 months. 6 pts had Gr >3 non-urinary any adverse events (AE) during treatment or within 12 weeks after completing treatment (2 with delay in RT >7 wks), and 2 pts had cisplatin dose reductions due to G2 AEs. 1 pt had G3 colitis, 1 pt had G2 polymyalgia, 1 pt G2 nephritis. Complete response (CR) rate 24 weeks post CRT was 88% (95% CI 68-99%, 21 CR, 3 PD, 3 NE). 8 pts developed metastatic disease & 3 other pts had non metastatic PD in the bladder/upper urinary tracts. Distant metastasis-free survival rate at 2 yrs is 78% (95% CI 54-90%) and rate of freedom from locoregional progression is 87% (95% CI 64-96%). Median OS is 39 months (95% CI: 17.1 - NE).
Conclusions
Addition of pembro to CRT for MIBC was feasible and does not appear to add unexpected toxicity. CRT with pembro results in promising CR rates at 6 months. Follow up & comparative studies are required to assess impact on OS and metastasis free survival.
Clinical trial identification
NCT02662062.
Editorial acknowledgement
Legal entity responsible for the study
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).
Funding
Merck & Co.
Disclosure
A.J. Weickhardt: Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck, Pfizer, Ipsen, Astellas, BMS; Financial Interests, Personal, Research Grant: BMS, Merck. A. Pal: Financial Interests, Personal, Advisory Board: BMS, Urogen; Financial Interests, Institutional, Research Grant: Telix, AstraZeneca. P. Grimison: Financial Interests, Institutional, Invited Speaker, GS-2475: Gilead; Financial Interests, Institutional, Invited Speaker, INCSHR01210: Tigermed; Financial Interests, Institutional, Invited Speaker: Pfizer, Boston Biomedical, MedImmune, Halozyme, Aslan Pharmaceuticals, Janssen, Prime Therapeutics, Epizyme, Plexxikon, Five Prime Therapeutics, Novartis, QED; Financial Interests, Institutional, Invited Speaker, Pembrolizmab: Merck; Non-Financial Interests, Project Lead, P3 accelerated BEP clinical trial: Australian and New Zealand Urogenital and Prostate cancer trials group (ANZUP) - non-commercial academic collaborative group; Non-Financial Interests, Leadership Role, TIGER clinical trial - Australia/New Zealand national lead investigator: Australian and New Zealand Urogenital and Prostate cancer trials group (ANZUP) - non-commercial academic collaborative group; Non-Financial Interests, Project Lead, Study chair for government-funded randomised trial of medicinal cannabis with free drug supply by Tilray: NHMRC Clinical Trials Centre, University of Sydney; Other, Member - role in decisions regarding reimbursement of drugs: Australian Government - Pharmaceutical Benefits Advisory Committee. E. Hovey: Financial Interests, Personal, Advisory Board: Ipsen, Merck, Janssen, Amgen; Financial Interests, Personal, Invited Speaker: Janssen. A. Guminski: Financial Interests, Personal, Advisory Board: Regeron, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Research Grant: Sun Pharma, AstraZeneca. B. Tran: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Bayer, BMS, Janssen, MSD, Novartis, Sanofi, Tolmar, Ipsen, IQVIA; Financial Interests, Personal, Speaker’s Bureau: BMS, Amgen, Astellas; Financial Interests, Personal, Other, Travel: Bayer. I.D. Davis: Financial Interests, Personal, Royalties, Authorship royalties for: Health Press; Financial Interests, Personal, Other, Remuneration for associate editor role in Therapeutic Advances in Medical Oncology: SAGE; Financial Interests, Institutional, Invited Speaker, Institutional support for clinical research: Movember Foundation, Merck/MSD, Bristol Myers Squibb, Exelixis, Astellas, Pfizer, AstraZeneca, Roche / Genentech, Eisai, Bayer, Janssen, Ipsen, Seagen; Non-Financial Interests, Invited Speaker, Director and Chair: ANZUP Cancer Trials Group; Non-Financial Interests, Advisory Role, All honoraria and payments are made directly to ANZUP Cancer Trials Group with no pass-through payment: Roche, Janssen, Astellas, Bayer, Ipsen, MSD, Merck/Pfizer, AstraZeneca, Eisai, Bristol Myers Squibb, Pio Therapeutics; Non-Financial Interests, Other, Member of Council: Clinical Oncology Society of Australia. D. Hayne: Financial Interests, Personal, Advisory Board, Advisory board participant: BMS; Financial Interests, Personal, Advisory Board, Ad board: Urogen; Financial Interests, Personal, Other, Travel support to present work at academic meeting: Telix; Financial Interests, Institutional, Invited Speaker, Funding for ZipUp Trial - unrestricted grant: Telix; Financial Interests, Institutional, Research Grant, Drug provided for SUBDUE-1 trial: AstraZeneca; Non-Financial Interests, Leadership Role, Chair BUP subcommittee, SAC member and OPS Exec member: ANZUP. All other authors have declared no conflicts of interest.