Dr Mouabbi on Clinical Trials for Invasive Lobular Breast Cancer

Jason A. Mouabbi, MD, assistant professor, Department of Breast Medical Oncology, Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses upcoming clinical trials aimed at expanding the treatment paradigm for patients with invasive lobular breast cancer.

Mouabbi highlights 3 notable studies currently running in this space. First, the phase 2 REPLOT trial (NCT06408168)is investigating the ROS1 inhibitor repotrectinib (Augtyro) with or without fulvestrant (Faslodex) in patients with hormone receptor–positive, HER2-negative metastatic invasive lobular carcinoma whose disease progressed following first-line therapy endocrine therapy that included a CDK 4/6 inhibitor. Mouabbi explains that this is the first clinical trial in the United States evaluating a ROS1 inhibitor such as repotrectinib in this setting, and he adds that enrollment is expected to initiate soon.

Another phase 2 study (NCT05919108) will investigate neoadjuvant neratinib (Neralynx) in combination with endocrine therapy for patients with stage I to III invasive lobular breast cancer harboring HER2 mutations. HER2 mutations are more common in patients with invasive lobular breast cancer, Mouabbi explains, noting that these appear in approximately 15% of patients compared with approximately about 5% of patients with ductal cancers. This trial aims to assess whether targeting HER2 mutations could provide a beneficial therapeutic approach for patients with lobular breast cancer, he says.

A third upcoming study called NeoAKT will investigate the neoadjuvant combination of capivasertib (Truqap) and letrozole in postmenopausal patients with stage II to III, estrogen receptor–positive, HER2-negative invasive lobular carcinoma. The study will enroll patients irrespective of mutation status, according to Mouabbi, as the trial seeks to include patients with early-stage lobular breast cancer to examine the potential of AKT inhibition in this patient population.

Mouabbi explains that in each of these studies could represent a critical step forward in addressing the unique characteristics of lobular breast cancer. Through exploring the use of more targeted therapies and combinations, these trials aim to enhance treatment efficacy and expand the options available for patients with this distinct form of breast cancer, he concludes.