ESMO Breast 2021 | ROSALINE: targeting ROS1 in combination with ET for breast cancer

Well, we presented at the ESMO Breast 2021 our trial-in-progress, ROSALINE. ROSALINE is a Phase II, single-arm, neoadjuvant study evaluating the combination of entrectinib plus endocrine therapy for patients with ER+/HER2- invasive lobular breast cancer. And the rationale behind the study is related to the fact that lobular breast cancer, which is second most common histotype in breast cancer after ductal breast cancer, is characterized by a different clinical course compared to ductal breast cancer. Because, for instance, it has a different clinical presentation, it tends to metastasize more often to the peritoneum, to the ovaries, to the GI tract and it has also lower response rate to conventional therapies. But nevertheless, in clinical practice lobular breast cancer is still treated similarly to ductal breast cancer.

And we know based on preclinical findings, that the loss of E-cadherin is a very frequent oncogenic event in lobular breast cancer. There are some in vivo studies showing a very strong antitumor effect of ROS1 inhibitors in the models with E-cadherin-defective breast cancer. And this provides a very strong rationale to test the ROS1 inhibitors in lobular breast cancer. So, that’s why in ROSALINE we are testing a ROS1 inhibitor, which is entrectinib in combination with endocrine therapy for patients with invasive lobular breast cancer.

More in detail, how our target population consists in women in pre or postmenopausal status with ER+/HER2- breast cancer of at least two centimeters, N0 or N1. And in the trial, all patients were receiving this neoadjuvant treatment consisting in entrectinib for four cycles, each cycle of 28 days, in combination with letrozole with or without goserelin. Of course, the goserelin only in premenopausal patients. And at the end of this neoadjuvant treatment, all patients will undergo surgery as per local guidelines.

So, our primary endpoint will be the evaluation of the residual cancer burden, 0/1 rate in all the enrolled the patients. And then we have some secondary endpoints, including the pathological complete response in breast and axilla in all the enrolled patients. The overall response rate assessed, has the local MRI and of course the safety of this new treatment combination. And moreover, we have also some exploratory endpoints which are basically aimed to identify differences between the responders and non-responders through a very extensive genomic and transcriptomic analysis which will be performed on samples collected both at baseline, meaning before the treatment, and after the treatment meaning that surgery.

Overall, we have 10 participating centers in ROSALINE in Belgium and France, and we have already eight patients enrolled in ROSALINE who are receiving their treatment. Regarding to ROSALINE, maybe I would like really to thank all the ROSALINE team. Starting from our study chair, Dr Philippe Aftimos. Of course, all the investigators, the CTCU team at the Institute Jules Bordet. And of course, all the patients enrolled in the study and their families as well.