Abstract 1751P
Background
UC with squamous differentiation (UCS) is the most common histologic variant of mUC but data on outcomes with recently approved drugs are limited. We compared molecular profiling and outcomes in UCS versus pure UC (pUC) pts treated with newer therapies such as immune checkpoint inhibitors (ICIs) and enfortumab vedotin (EV).
Methods
We undertook a retrospective analysis of mUC pts treated with ICI or EV at UCSF between 12/2014 and 3/2022. Objective response rate (ORR), progression free survival (PFS) and overall survival (OS) were compared between pUC and UCS pts using Chi-Square and log-rank tests. Tumor mutation burden (TMB), PD-L1 status and somatic alterations in >10% of pts were also compared.
Results
Among 160 pts (120 pUC, 40 UCS), 151 were treated with ICI (113 pUC, 38 UCS) and 37 pts with EV regimens (25 pUC, 12 UCS). pUC pts were younger (median age 68 vs 74 years, p=0.04); other baseline characteristics were well balanced. Next generation sequencing (NGS) was available in 115 (72%) pts and PD-L1 status in 55 (34%) pts. UCS pts had a higher incidence of CDKN2A (71 vs 33%, p=0.001), CDKN2B (58 vs 26%, p<0.01), and PIK3CA (36 vs 12%, p<0.01), and fewer ERBB2 alterations (3 vs 20%, p=0.05) relative to pUC. No differences in TMB or PD-L1 status were observed. Median follow-up from metastatic (met) diagnosis was 15.7 (1.1 to 86.4) months (mos) for all pts. UCS pts had shorter OS from met diagnosis (14.6 vs 25.4 mos, p=0.02). Among ICI-treated pts, UCS pts had inferior PFS (p<0.001) and OS (p<0.01) from ICI start compared to pUC (Table). UCS pts treated with EV had a lower ORR (p<0.01) and inferior PFS (p<0.01). Table: 1751P
| ICI (n=151) | EV (n=37) | |||||
| pUC (n=113) | UCS (n=38) | p-value | pUC (n=25) | UCS (n=12) | p-value | |
| ORR, % | 38 (29, 47) | 21 (8, 34) | 0.102 | 70 (52, 88) | 17 (2,48) | <0.01 |
| Median PFS,1 mos | 4.8 (3.3, 11.7) | 1.9 (1.6, 3.1) | <0.001 | 15.8 (8.1, NR) | 3.4 (2.6, NR) | <0.01 |
| Median OS, 1 mos | 20.7 (14.1, 34.7) | 9.2 (3.2, 25.6) | <0.01 | 24.0 (15.8, NR) | 15.5 (5.32, NR) | 0.473 |
1From systemic therapy start
Conclusions
In this large single-center retrospective analysis, UCS pts had a distinct somatic genomic profile and inferior outcomes to ICI and EV compared to pUC pts. Prospective validation is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Fong: Financial Interests, Institutional, Funding: AbbVie, Amgen, Bavarian Nordic, BMS, Dendreon, Janssen, Merck, Roche/Genentech. T. Friedlander: Financial Interests, Institutional, Funding: Seagen. V.S. Koshkin: Non-Financial Interests, Institutional, Advisory Role: AstraZeneca, Clovis, Janssen, Pfizer, EMD Serono, Seagen, Astellas, Dendreon, Guidepoint, GLG, ExpertConnect; Financial Interests, Institutional, Funding: Endocyte, Nektar, Clovis, Janssen, Taiho; Financial Interests, Institutional, Other, Support: Prostate Cancer Foundation. All other authors have declared no conflicts of interest.