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Research frontier| efficacy of EphB2 inhibitors combined with PD-1 monoclonal antibody in mUC

 Last Update: 2022-11-05
 Source: Internet
 Author: User

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Guide

Bladderurothelial carcinoma is a common tumor in urology, and the 5-year survival rate of newly diagnosed patients is low, while the median survival of patients after first-line platinum-based chemotherapy is about 1 year, and the prognosis is poor
.
PD-1/PD-L1 antibodies have been found to be less effective in metastatic urothelial carcinoma (mUC) than in other tumors, so new treatment options
need to be explored.
Foreign researchers have carried out relevant research, and the medical pulse is summarized as follows
.

background

EphB4 is highly expressed in urothelial carcinoma, and EphB4 receptor tyrosine kinase and its high-affinity ligand EphB2 are potential therapeutic targets
.
Preclinical studies have confirmed that the EphB2 inhibitor, EphB4-human serum albumin (sEphB4-HAS), in combination with PD-1 monoclonal antibody, is more effective than monotherapy
.
Therefore, the investigators evaluated the efficacy
of sEphB4-HAS in combination with pembrolizumab in platinum-refractory mUC.

Research methods

This is a phase II study that included patients with mUC who relapsed or progressed after platinum-containing chemotherapy and received a combination of
sEphB4-HAS and pembrolizumab.
The primary study endpoints were tolerability and overall survival (OS).

Secondary endpoints included: progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity
.

Research results

A total of 70 patients were included in the study, with a median age of 67 years and a median duration of treatment of 15 weeks
.
Of these, 46 patients were EphrinB2-positive
.

The median OS for patients was 14.
6 months (95% CI 9.
2 to 21.
5 months); The median OS for 46 patients with positive biomarker EphrinB2 expression was 21.
5 months (95% CI 12.
4 - not yet achieved, median follow-up 22.
5 months).

Fig.
1 OS and PFS results of patients

Of the 70 patients with intention-to-treat (ITT), 26 achieved objective responses
.
The ORR rate for 63 patients with evaluable response was 41% (95% CI 29% to 54%), of which the complete response rate was 18% (95% CI 8% to 27%)
.
Results of population analysis of ITT showed a median PFS of 4.
1 months (95% CI 1.
5 to 5.
7 months).

EphrinB2-positive patients (N=46) had an ORR of 52% (95% CI 37% to 67%), with a complete response rate of 24% (95% CI 12% to 36%), and a median PFS of 5.
7 months (95% CI 2.
7 to 27.
9 months).

Patients who achieved remission (N=26) had response rates of 88%, 74%, and 69%
at 6, 12, and 24 months, respectively.

conclusion

sEphB4-HAS and pembrolizumab have synergistic effects, and compared with historical data on PD-1 monoclonal antibody monotherapy, this regimen performs better in OS and ORR, and it is expected to bring greater benefits
to patients in clinical applications.

References

Sadeghi S, Quinn D, Dorff T, Pal S, Groshen S, Tsao-Wei D, Parikh R, Devitt M, Parikh M, Jackovich A, Ruel N, Vogelzang N, Burgess E, Siddiqi I, Gill IS, Lara PN, Dreicer R, Gill PS.
EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma.
J Clin Oncol.
2022 Aug 19:JCO2102923.

Editor: LR Review: LR Execution: Uni

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