Challenging Endocrine Sensitivity of Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with the Combination of Eribulin and Endocrine Therapy: The REVERT Study

SIMPLE SUMMARY: Acquiring of resistance is a common outcome after prolonged cancer treatment and consecutive treatments are, in general terms, limited. Here we published the results of REVERT clinical study that aimed to REVERT the resistance to hormonal treatment that often occurs in breast cancer patients positive for hormone receptors. According to previous published data, adding drug called eribulin to hormonal treatment may sensitized the tumor to the hormonal treatment due to switch of cancer cell phenotype. Even though this theory was not proved in this study, the outcomes of this study open a new door for further investigation since the results suggests that the patients treated with hormonal therapy and inhibitors of cyclins may have further clinical benefit, if eribulin is added to the therapy. Importantly, no additional unexpected side effects were reported with this drug combination. ABSTRACT: Background: Luminal advanced breast cancer (ABC) patients eventually progress on endocrine therapy. REVERT aimed to explore whether eribulin could restore endocrine sensitivity in a randomized, non-comparative phase II trial. Methods: Aromatase inhibitor (AI)-resistant patients with luminal ABC were randomized 1:1 to receive eribulin +/− AI. Patients were stratified by prior cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) treatment. The primary endpoint was an investigator-assessed overall response rate (ORR) according to RECIST version 1.1 in the eribulin + AI arm. An interim analysis was planned with 11 evaluable patients according to a two-stage Simon design. Results: Twenty-two patients were enrolled (15 eribulin + AI arm; 7 eribulin arm). The trial was terminated early in March 2021, with eight (36.4%) patients still on treatment. ORR was 26.7% in the eribulin + AI arm (95% CI, 7.8–55.1%; p = 0.0541). In the eribulin arm, two (28.6%) patients had an objective response (95% CI, 3.7–71.0%). The difference between the study arms was not significant (p = 0.918). The addition of AI to eribulin also failed to show improvement in other efficacy endpoints. A significant interaction between the treatment arm and previous CDK4/6i treatment was observed for ORR (p = 0.018) and progression-free survival (p = 0.084). Overall, the toxicity profile was consistent with the known safety profile of eribulin. No treatment-related deaths were reported. Conclusion: Eribulin + AI does not seem to improve outcomes compared with eribulin monotherapy in patients with AI-resistant luminal ABC. This chemo–endocrine approach deserves further investigation after progression to CDK4/6i-based therapy.