Abstract 8P
Background
EV is approved in patients (pts) with aUC; however, not all pts respond to EV, with some experiencing primary progressive disease (PPD). Such pts can be prioritized for other treatments (tx). We hypothesized that PPD on EV can be predicted by a pt’s clinical characteristics, prior tx and tumor molecular profiling.
Methods
UNITE is a multi-site retrospective study of pts with aUC treated with EV and/or other agents. In this analysis, pts treated with EV monotherapy and evaluable for response (at least 1 cycle of EV) were divided into pts with PPD (PD as best response) and Non-PPD pts (CR/PR/SD as best response). Clinical factors, somatic genomic alteration (alts) data from next generation sequencing (NGS) platforms, and prior tx lines were compared among the 2 groups; χ2 test was used to compare differences in proportions. Overall survival (OS) from EV start was compared with KM method.
Results
Among 488 pts (124 PPD; 364 non-PPD) across 17 US sites, median age was 71, 71% men, 67% pure urothelial histology, 80% lower tract tumor, and 28% liver mets. No significant differences in clinical characteristics were found between pts with non-PPD and PPD. Median follow up was 21.1 mos from EV start, mOS was 13.3 mos; ORR to EV was 49%. Pts with PPD had shorter mOS vs pts with non-PPD from EV start (5.3 vs 16.1 mos; p <0.01). Pts with PPD were more likely to get platinum-based chemotherapy and less likely to get immune checkpoint inhibitor as tx immediately prior to EV; comparisons with prior tx are shown in the table. NGS data was available for 374 pts (276 non-PPD; 98 PPD). Pts with PPD had a higher rate of CDKN2B alts vs non-PPD pts (19% vs 12%; p = 0.05). Table: 8P
| Non-PPD (N=364) | PPD (N=124) | p-value | |
| Lines of tx before EV 0/1 2 or more | 117 (32%) 247 (68%) | 42 (34%) 82 (66%) | N/A |
| Tx immediately prior to EV | |||
| Immune checkpoint inhibitor (ICI) | 236/300 (79%) | 57/95 (60%) | <0.01 |
| Platinum-based chemotherapy (PBC) | 35/205 (17%) | 25/76 (33%) | <0.01 |
| Best response to tx immediately prior to EV | |||
| PD on tx | 136/315 (43%) | 45/102 (44%) | 0.87 |
| Non-response (SD/PD) on tx | 222/315 (70%) | 76/102 (75%) | 0.43 |
| Best response to prior PBC | |||
| PD on tx | 44/210 (21%) | 24/79 (30%) | 0.09 |
| Non-response (SD/PD) on tx | 102/210 (49%) | 42/79 (53%) | 0.49 |
| All prior tx best response (for pts with 2 or more prior tx) | |||
| PD on all prior tx | 29/237 (12%) | 15/79 (19%) | 0.13 |
| Non-response (SD/PD) on all prior tx | 94/237 (40%) | 37/79 (47%) | 0.26 |
Conclusions
This large retrospective analysis suggests that prior therapies and NGS data may help identify pts with PPD on EV tx. Limitations include retrospective nature, lack of central scan review, and selection bias. These hypothesis-generating findings require further validation in larger cohorts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
O. Alhalabi: Financial Interests, Personal, Advisory Board: Seagen, Silverback therapeutics, Cardinal health; Financial Interests, Personal, Invited Speaker: Curio Science, Ikena Oncology, Arcus Biosciences; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Genentech. A. Nizam: Financial Interests, Personal, Advisory Board: AVEO Pharmaceuticals, Inc.; Financial Interests, Personal, Invited Speaker: Cleveland Clinic Foundation; Financial Interests, Personal, Other: Aptitude Health, Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology / Association for Clinical Oncology PAC. Y. Zakharia: Financial Interests, Personal, Advisory Board: Pfizer, Eisai, Exelixis, Myovant, BMS. J. Brown: Financial Interests, Personal, Invited Speaker, Speaker's Bureau for Avelumab: EMD Serono; Financial Interests, Personal, Invited Speaker, Speaker for MSL Training: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Jounce Pharmaceuticals, Seattle Genetics, Novita, Bicycle Therapeutics, Roche. D. Kilari: Financial Interests, Personal, Invited Speaker: Janssen, Pfizer, Aveo oncology, Seagen, MJH - life sciences; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Institutional, Invited Speaker: Exelixis, Genentech, Jounce. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Seattle Genetics, Janssen, Aveo, Cardinal Health. S. Gupta: Financial Interests, Personal, Advisory Board: Seattle Genetics, BMS, Pfizer, Bayer, Merck, Gilead, Loxo Oncology, Guardant, Foundation one; Financial Interests, Personal, Other, Speaker's Bureau: Janssen; Financial Interests, Personal, Other, Consultant: EMD Serono; Financial Interests, Personal, Invited Speaker: Gilead, BMS, Merck, Seattle Genetics, Acrivon; Financial Interests, Personal, Stocks/Shares: BioNTech, Moderna; Financial Interests, Institutional, Invited Speaker: EMD Serono, Gilead, Roche, QED, Exelixis, Moderna, Pfizer. P. Grivas: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Bristol Myers Squibb, Asieris Pharmaceuticals, Merck KGaA, Seattle Genetics, Aadi Bioscience, Pfizer, Janssen, Boston Gene, Mirati Therapeutics, Exelixis, Genentech/Roche, Gilead Sciences, CG Oncology, Dyania Health, Infinity Pharmaceuticals, QED Therapeutics, 4D Pharma PLC, ImmunityBio, Lucence Health, G1 Therapeutics, Fresenius Kabi, Guardant Health, PureTech, Regeneron Pharmaceuticals, Strata Oncology, Urogen, Silverback Therapeutics, Astellas Pharma; Financial Interests, Institutional, Invited Speaker: Pfizer, Clovis Oncology, Bavarian Nordic, Gilead Sciences, Bristol Myers Squibb, Debiopharm Group, MSD, QED Therapeutics, GSK, Mirati Therapeutics, G1 Therapeutics, Merck KGaA. J. Bellmunt: Financial Interests, Personal, Advisory Board, Joined the Global Ad. Board this year: Pfizer; Financial Interests, Personal, Advisory Board, Regular GU Ad. Board for bladder cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures in the setting of National meetings: Merck; Financial Interests, Personal, Advisory Board, Bladder Ad. Board: 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, Invited Speaker, Pi of INDUCOMAIN Study (Avelumab first line in unfit patients) Though APRO Association: MSD; Financial Interests, Institutional, Invited Speaker, 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. M.T. Campbell: Financial Interests, Personal, Advisory Board: Exelixis, Pfizer, Seagen, AstraZeneca, Curio Science, Eisai; Financial Interests, Institutional, Invited Speaker: Pfizer, Exelixis, Aravive, Janssen, Seagen. V.S. Koshkin: Financial Interests, Personal, Advisory Board: Janssen, Clovis, Astellas, AstraZeneca, Pfizer, EMD Serono; Financial Interests, Personal, Other, Consulting: GLG, ExpertConnect, Guidepoint; Financial Interests, Institutional, Invited Speaker: Merck, Seagen, Taiho, Eli Lilly, Clovis, Novartis; Financial Interests, Personal and Institutional, Research Grant: Prostate Cancer Foundation. All other authors have declared no conflicts of interest.