Disitamab Vedotin Combos Are Effective in HER2+, HER2-Low Breast Cancers


Disitamab vedotin either alone or with TKIs, ICIs, or other antiangiogenic agents were consistently effective in patients with HER2-positive or -low breast cancers.

Disitamab Vedotin Combos Are Effective in HER2+, HER2-Low Breast Cancers

Disitamab Vedotin Combos Are Effective in HER2+, HER2-Low Breast Cancers

Patients with HER2-positive or HER2-low locally advanced or metastatic breast cancer treated either with disitamab vedotin (RC48-ADC) alone or paired with immune checkpoint inhibitors (ICIs), TKIs, or other antiangiogenic compounds experienced consistent tolerability and efficacy, according to findings from a single-arm phase 2 study presented at the 2023 San Antonio Breast Cancer Symposium.

Treatment with the recombinant, humanized antibody-drug conjugate led to a median progression-free survival (PFS) of 5.7 months (95% CI, 4.6-6.9) in the overall patient population (n = 120). Moreover, the overall response rate (ORR) was 38.3% (95% CI, 30.0%-47.3%), which comprised 5 complete responses (CRs) and 41 partial responses (PRs); 21 patients achieved stable disease (SD). The disease control rate (DCR) reported in this group was 64.2% (95% CI, 54.9%-72.6%).

In the HER2-positive subgroup (n = 82), median PFS was 6.3 months (95% CI, 4.9-7.6). In this group, the agent induced an ORR of 42.7% (95% CI, 32.0%-54.1%), which included 5 CRs and 30 PRs; 21 patients had SD. In the HER2-low subgroup (n = 38), the median PFS was 3.6 months (95% CI, 2.0-5.3). In these patients, the ORR was 29.0% (95% CI, 16.0%-46.1%); no CRs were reported, but 11 patients experienced PRs. A total of 10 patients had SD.

“Coadministration with ICIs, TKIs, and antiangiogenic compounds demonstrated substantially enhanced efficacy compared [with] monotherapies and could be a future direction in development of [the] ADC,” Fei Qu, MD, of the First Affiliated Hospital of Nanjing Medical University, Nanjing, in Jiangsu, China, and colleagues, wrote in a poster of the data.

Although HER2-targeting agents have improved outcomes in HER2-positive metastatic breast cancer, acquired resistance continues to lead to disease progression for most patients. The current third-line or later options available to patients with HER2-positive disease have provided limited clinical benefit. According to the study authors, treatment strategies utilized for those with HER2-low disease are comparable to those used in patients with HER2-negative disease, and no recommended targeted option is available has been determined for the former subgroup.

Disitamab vedotin is comprised of hertuzumab which acts against HER2, monomethyl auristatin E (MMAE), and a cleavable linker; it has a bystander effect in tumor cell killing.

The objective of the open-label, single-arm study was to address the limited data that are available regarding the use of disitamab vedotin in patients with breast cancer and to acquire insights on the treatment patterns of the ADC in China.

Eligible patients had histopathologically- or imaging-confirmed invasive locally advanced or metastatic breast cancer, pathologically confirmed HER2-positive or -low disease, at least 1 extracranial measurable lesion or osteolytic or mixed bone metastases based on RECIST 1.1 criteria, and untreated brain metastases or treated and progressive brain metastases. To participate, patients needed to be aged 18 years or older, have an ECOG performance status of 3 or less, and have clinical data that was complete and traceable.

Participants were treated with the ADC at 2.5 mg/kg once every 2 weeks alone or in combination with other ICIs, TKIs, and antiangiogenic compounds.

The primary end points of the study were PFS and ORR, and secondary end points included DCR, OS, and safety.

The median patient age was 53 years (range, 23-84). Eighty percent of patients were under the age of 60 years and the remainder were 60 years of age or older. More than half of patients (72.5%) had an ECOG performance status of 0 or 1, and the remaining 27.5% had an status of 2 or higher. Additionally, 82.5% of patients had recurrent disease from earlier stages (I to III) and 17.5% of patients had de novo or newly diagnosed stage IV disease. The burden of the primary breast tumor lesion was less than 5 cm in 65.8% of patients and 5 cm or greater in 34.2% of patients. Most patients (86.7%) had metastatic lymph node involvement.

Moreover, 44.2% of patients had estrogen receptor (ER) negativity and the remainder had ER positivity; 58.3% and 41.7% of patients had progesterone negativity and positivity, respectively. In terms of HER2 expression, 10% of patients had a status of IHC 1+, 21.7% were IHC 2+/ERBB2 ISH-negative, 22.5% were IHC 2+/ERBB2 ISH-positive, and 45.8% were IHC 3+. Regarding lines of advanced systematic therapy of the ADC, 3.3% of patients had 1 line, 8.3% of patients had 2 lines, and 88.3% of patients had 3 or more lines. Just under half of patients (41.7%) had less than 4 metastatic sites and the remainder had 3 or more.

“The median PFS in the dual drug combination-treated group were longer than those in the single-drug treatment group, with a median PFS of 7.1 months [95% CI, 5.0-9.2] and 4.6 months [95% CI: 3.5-5.8], respectively,” the study authors noted.

Overall, the most frequently reported treatment-related adverse effects (TRAEs) were increased aspartate aminotransferase (45.8%), increased alanine aminotransferase (41.7%), decreased white blood cell count (25.0%), and fatigue (25%). Most of these effects were grade 1 or 2 in severity.


Qu D, Yin Y, Li W, et al. Efficacy and safety of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48- ADC in patients with HER2-positive or HER2-low expressing, locally advanced or metastatic breast cancer: a single-arm phase II study. Presented at: San Antonio Breast Cancer Conference; December 5-9, 2023; San Antonio, TX. Poster PO3-04-05

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