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Observational Study
. 2023 Dec;12(23):21159-21171.
doi: 10.1002/cam4.6680. Epub 2023 Nov 7.

Real-world effectiveness and safety of RC48-ADC alone or in combination with PD-1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study

Jingwei Xu  1 , Hongqiao Zhang  1 , Li Zhang  1 , Xiufeng Chu  1 , Yu Li  1 , Guangyuan Li  1 , Caiyun Nie  2 , Meng Wang  3 , Yanwei Guo  1   4
Affiliations
Observational Study

Real-world effectiveness and safety of RC48-ADC alone or in combination with PD-1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study

Jingwei Xu et al. Cancer Med. 2023 Dec.

Abstract

Introduction: Previous RC48 (Disitamab Vedotin) studies established that the safety and efficacy of RC48-antibody-drug conjugate (ADC), either alone or combined with toripalimab, for metastatic urothelial carcinoma (mUC) patients exhibiting human epidermal growth factor receptor 2 (HER2)-positive or even HER2-negative status after standard chemotherapy failure.

Methods: With locally advanced or metastatic urothelial carcinoma (la/mUC), patients who received RC48-ADC monotherapy or a combination with programmed cell death protein 1 (PD-1) inhibitors between August 2021 and October 2022 were enrolled in this retrospective observational study to evaluate the real-world antitumor effectiveness and safety.

Results: Among the 38 enrolled patients (29 males; median age 67.5 years [38-93]), 8 received RC48-ADC monotherapy, while 30 received combination therapy. Initially, 63.2% (24/38) of the patients had received ≥1 line of prior treatment, and 63.2% (24/38) had visceral metastasis. UC of the bladder represented the majority type in 68.4% (26/38) of cases. By the data cutoff in March 2023, the overall objective response rate (ORR) was 63.2% (95% CI, 47.1%-79.2%), with a disease control rate (DCR) of 89.5% (95% CI, 79.3%-99.7%). Median follow-up time was 10.6 months. The median progression-free survival (PFS) was 8.2 months (95% CI, 5.9-10.5), with a 6-month PFS rate of 63.2% and a 12-month PFS rate of 34.1%. Median overall survival (OS) was not reached, with a 12-month OS rate of 76.7%. The median duration of response was 7.3 months (95% CI, 4.6-10.0) among 24 patients evaluated as partial response (PR). The most common treatment-related adverse events (TRAEs) included anemia (71.1%), anorexia (57.9%), asthenia (52.6%), hypoesthesia (52.6%), bone marrow suppression (47.4%), alopecia (47.4%), nausea (44.7%), proteinuria (36.8%), vomiting (34.2%), and hypoalbuminemia (31.6%). No patient experienced TRAEs of Grade ≥3. One patient had an immune-related adverse event (irAE) of rash related to toripalimab.

Conclusions: Both as monotherapy and in combination with PD-1 inhibitors, RC48-ADC exhibits promising effectiveness and manageable safety profile for mUC patients in real-world settings.

Keywords: antibody-drug conjugate; disitamab vedotin; metastatic urothelial carcinoma; real-world study.

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Conflict of interest statement

The authors indicate no financial or non‐financial interests.

Figures

FIGURE 1
FIGURE 1
(A) PFS and (B) OS curves for all patients. (C) PFS curves for patients who received RC48 as the first‐line treatment group and ≥2nd‐line treatment group, respectively. (D) PFS curve for patients who received a combination therapy of RC48‐ADC and PD‐1 inhibitors. (E) PFS curves for patients who received combination therapy as the first‐line treatment group and ≥2nd‐line treatment group, respectively. (F) PFS curves for patients who received different combination therapies.
FIGURE 2
FIGURE 2
Swimmer plot for response evaluation. Start 1 means the time when the patient was first evaluated as PR.
See this image and copyright information in PMC

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