| Autor: |
Chi Leung Chiang, Tai Chung Lam, James Chun Bong Li, Kenneth Sik Kwan Chan, Aya El Helali, Yolanda Yim Ping Lee, Laalaa Hiu Ting Law, Danyang Zheng, Anthony Wing Ip Lo, Ngar Woon Kam, Wing Sum Li, Alice Ka Wai Cheung, James Chung Hang Chow, Sunny Po Chung Chan, Jessica Wing Yu Lai, Sarah Wai Man Lee, Feng-Ming (Spring) Kong, Wai Tong Ng, Dora Lai Wan Kwong, Anne Wing Mui Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
The Lancet Regional Health. Western Pacific, Vol 40, Iss , Pp 100898- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2666-6065 |
| DOI: |
10.1016/j.lanwpc.2023.100898 |
| Popis: |
Summary: Background: The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFβ1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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