Discussion
TEAEs, TAntitumor, rash
EVENTS, METASTASES, METASTATIC BREAST CANCER
The AMEERA-2 study has demonstrated that amcenestrant has a favorable safety profile in Japanese postmenopausal women with ER + /HER2 − advanced breast cancer, with no grade ≥ 3 TEAEs at a dose of 400 mg QD and a PK profile similar to the one previously observed in a global population of patients (AMEERA-1, Arm 1, Part A). Amcenestrant 400 mg QD has subsequently been selected as the recommended Phase II dose for monotherapy. The previous AMEERA-1 dose escalation study (Arm 1, Part A) which assessed amcenestrant doses of 20, 150, 200, 400, and 600 mg QD showed that amcenestrant was rapidly absorbed (median TIn AMEERA-2, most patients were aged > 65 years, had metastases, and were heavily pre-treated (prior therapy received: hormonal therapy and/or chemotherapy and/or targeted therapy). While no DLT was reported in patients treated with amcenestrant 400 mg QD, one DLT (grade 3 maculopapular rash) was reported in a patient treated with amcenestrant 300 mg BID. These findings contrast with those from the AMEERA-1 study wherein no DLTs and no related grade ≥ 3 events were reported with amcenestrant up to 600 mg QD and 300 mg BID [The preliminary safety profile of amcenestrant in Japanese postmenopausal women in AMEERA-2 was generally comparable with that reported for the AMEERA-1 study [In the present study, amcenestrant absorption was observed without TAntitumor activity was demonstrated in seven evaluable patients (ORR: two [28.6%] out of seven patients; CBR: four [57.1%] out of seven patients), and this was comparable with that reported in AMEERA-1 part B (ORR and CBR: five [10.9%] and thirteen [28.3%] out of 46 patients respectively) [Small number of patients is a limitation of AMERA-2 study and therefore, caution is required when making any conclusions based on the available antitumor activity and biomarker data, with all findings requiring further evaluation and confirmation.In summary, data from AMEERA-2 provide a basis for evaluating the safety and efficacy of 400 mg QD amcenestrant in a larger, global, randomized clinical trial of patients with metastatic breast cancer, including those from Japan (AMEERA-3; NCT04059484). However, AMEERA-3 trial did not meet primary endpoint of improving progression-free survival. Further, in AMEERA-5 trial, amcenestrant did not meet the prespecified boundary for continuation and therefore, Sanofi has discontinued the global clinical development program of amcenestrant.
