2003P - Clinical outcomes of patients with metastatic urothelial carcinoma (mUC) discontinuing enfortumab vedotin (EV) monotherapy (mono) without disease progression

Background

EV is routinely given until disease progression or unacceptable toxicity, the latter reported in 12-15% of patients (pts) in the EV mono trials, most commonly due to peripheral neuropathy (PN). Data is scarce regarding the outcomes of pts stopping EV while disease is controlled.

Methods

A single center retrospective cohort of all mUC pts treated with EV mono was reviewed to identify pts that achieved disease control per physician assessment [complete response (CR), partial response (PR) or stable disease (SD)] and stopped EV for toxicity without disease progression. Progression free survival (PFS) defined from last EV dose was calculated using Kaplan-Meier method and compared using logrank test.

Results

57 of 351 pts met the inclusion criteria. 77% male, median age 75 years (range 50-89), 63% bladder primary, most were post platinum (82%) and immunotherapy (89%). Lung, liver and bone metastases rates were 37%, 32% and 30%, respectively. Median time on EV was 5 months (mo), with CR, PR and SD achieved in 28%, 58% and 14% of pts, respectively. The most common causes for stopping EV were PN (72%), fatigue (25%) and rash (11%). Median follow-up from last EV dose was 20 mo (range 4-63). Median PFS was 7 mo (95% CI 3–14). There was significant difference between response groups (p<0.001), with increased risk of progression for both PR (mPFS 5 mo [95% CI 3-12]; HR 2.93 [95% CI 1.19, 7.21]) and SD (mPFS 2 mo [95% CI 1-NR]; HR 10.1 [95% CI 3.31, 30.7]) compared to CR (mPFS 30 mo [95% CI 13-NR]). Splitting by tertiles, long time on EV (>8.5 mo) was associated with better PFS compared to short (<3.7 mo) and intermediate (3.7-8.5 mo) duration (p <0.001). In PR pts, there was a significantly increased risk of progression with short (4.34 [95% CI 1.35, 14.0], p-0.014) and intermediate (6.28 [95% CI 1.94, 20.4], p-0.002) compared to long EV duration. There was no significant difference between short and intermediate by logrank test (p-0.4). In pts with CR and SD no distinct difference was detected.

Conclusions

In a subset of pts stopping EV without disease progression, best response and time on EV > 8.5 mo were associated with improved PFS after EV discontinuation. Further investigations are warranted to validate this observation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.Y. Teo: Financial Interests, Personal, Other, Equity: Clovis Oncology; Financial Interests, Personal, Other, Professional Services and Activities: Janssen Global Services, LLC. D. Bajorin: Financial Interests, Personal and Institutional, Other, Professional Services and Activities: Bristol Myers Squibb, Merck & Co Inc. R. Kotecha: Non-Financial Interests, Personal, Other, Professional Services and Activities (Uncompensated): Allogene Therapeutics; Other, Personal, Other, Professional Services and Activities: Eisai, Guidepoint Global Advisors, Kidney Cancer Journal; Non-Financial Interests, Personal, Advisory Board, Professional Services and Activities (Uncompensated): Pfizer, Inc.. A.L. Laccetti: Financial Interests, Personal, Advisory Board: Guidepoint; Financial Interests, Personal, Advisory Board, Health tech company. Advisory role on wearable devices in oncology care: Musculo; Financial Interests, Personal, Invited Speaker: Dava Oncology; Financial Interests, Institutional, Invited Speaker, Travel stipend for abstract presentation: Bayer; Financial Interests, Personal, Stocks/Shares, Stock option: Musculo; Financial Interests, Personal, Coordinating PI: ESSA Pharmaceuticals; Financial Interests, Personal, Steering Committee Member: Bayer Pharmaceuticals; Financial Interests, Personal, Local PI: Essa Pharmaceuticals; Financial Interests, Personal, Research Grant: Johnson & Johnson. D.J. McHugh: Other, Personal, Other, Professional Services and Activities: OncLive; Non-Financial Interests, Personal, Other, Professional Services and Activities (Uncompensated): Society of Nuclear Medicine and Molecular Imaging. S.A. Funt: Financial Interests, Personal, Other, Equity: 76Bio, Inc., Allogene Therapeutics, ByHeart, Inc., Doximity, Inc., IconOVir Bio, Inc., Kronos Bio, Inc, Neogene Therapeutics Inc, UroGen Pharma, Inc., Vida Ventures, LLC; Other, Personal, Other, Professional Services and Activities: BioNTech, Merck Sharp & Dohme; Non-Financial Interests, Personal, Other, Professional Services and Activities (Uncompensated): Immunai Inc.. N.J. Shah: Other, Personal, Other, Professional Services and Activities: Aravive, Inc., Exelixis, MedNet, Merck & Co Inc., Targeted Oncology. G. Iyer: Financial Interests, Personal, Advisory Board: Flare Therapeutics, EMD Serono, Loxo @ Lilly, Aadi Biosciences, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, Curio Science, Jaansen; Financial Interests, Institutional, Local PI: Aadi Biosciences, AstraZeneca, Flare Therapeutics, Pfizer, Loxo @ Lilly, Tyra. D.H. Aggen: Financial Interests, Personal, Other, Professional Services and Activities: Alpha Insights, Aptitude Health, Bristol Myers Squibb, Guidepoint Global Advisors, MJH Life Sciences, RC Horowitz & Co, Seagen; Financial Interests, Personal, Other, Intellectual Property Rights: University of Illinois. J.E. Rosenberg: Financial Interests, Personal, Advisory Board: Aadi Biosciences, Alligator Biosciences, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, EMD-Serono, Genentech, Gilead, IMVax, Janssen, Lilly Oncology, Merck, Mirati, NCCN, Pfizer, Tyra Biosciences, Aktis, Samsung Bioepis, Century Therapeutics, Bayer, Kalivir; Financial Interests, Personal, Invited Speaker, Medical Education: Clinical Care Options, Peer Direct; Financial Interests, Personal, Invited Speaker, Medical education: MJH Associates, Physicians Education Resource, Research to Practice; Financial Interests, Personal, Invited Speaker: Pfizer, Medscape, Mashup Media; Financial Interests, Personal, Advisory Board, + travel funding to attend meeting: Seagen; Financial Interests, Personal, Royalties: Wolters Kluyer/Uptodate; Financial Interests, Institutional, Coordinating PI, Coordinating PI of rogaratinib/atezolizumab trial; consultant: Bayer; Financial Interests, Personal and Institutional, Steering Committee Member, EV-201, EV- 103; consultant, trial open at my institution: Seagen; Financial Interests, Personal and Institutional, Steering Committee Member, EV-301, consultant, trial open at my institution: Astellas; Financial Interests, Personal and Institutional, Coordinating PI, Consultant, PI of trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, PI of IMVIGOR210 (still open at my institution): Genentech; Financial Interests, Institutional, Coordinating PI, PI of trial, consultant to company: Loxo Oncology; Non-Financial Interests, Leadership Role, Genitourinary Committee Chair: Alliance for Clinical Trials in Oncology. All other authors have declared no conflicts of interest.