345P Optimal Dose of Eribulin As First Line Treatment in Elderly Patients ≥ 70 Years with Advanced Breast Cancer: A Multicenter Phase II Trial [SAKK 25/14]

In elderly patients (pts) with metastatic breast cancer (mBC), there is no generally accepted 1st line chemotherapy (CT) and only scarce data on any CT regimen. Eribulin mesylate (1.4 mg/m2) in first line mBC achieved a clinical benefit rate (CBR; CR, PR or SD ≥ 6 months (mts)), of 26 - 52%. Less than 10% of pts in the registration-trial were ≥ 70 years (y); dose reductions were frequent in the elderly. We hypothesized: a reduced dose with less toxicity will lead to longer treatment duration and comparable CBR to the standard dose. Single-arm 2-stage phase II trial investigating a reduced starting-dose of eribulin mesylate 1.1 mg/m2 d1+8 q3wk in pts ≥ 70y with CT-naïve mBC. Disease control rate at 6 mts (CBR) was the primary endpoint. A Simon’s optimal single arm two-stage design to test H0 (CBR ≤ 35%) against H1 (CBR ≥ 50%) with a type-I error of 0.05 and power of 80% required 77 pts. Patient reported on neuropathy (FACT/GOG-Ntx) at the start of each cycle. From Aug 2015 to Feb 2019, 77 pts were accrued. Median (m) age was 76y (70-89); PS 0-1 in 90%, PS 2 in 10%; 64% had co-morbidities; 45% liver metastases, 3% bone-only disease. CBR was 40% (90% CI 31-50), ORR 22% (95%CI 13-33), mPFS 5.4 mts (95% CI 4.5-7.7) and mOS 16.1 mts (95% CI 13.5-26.9). The median number of cycles was 6 (1-24); dose modifications were necessary in 35% of pts; median dose per cycle was 2.1 mg/m2 (1.1-2.3). In 9 pts, >15 cycles were given. Main reasons for treatment discontinuation were progressive disease (57%), patient refusal (14%) and unacceptable toxicity (11%). Neutropenia G3 occurred in 10%, G4 in 12% of pts. Two pts (3%) suffered febrile neutropenia. Sensory neuropathy in 23% was usually mild (12% G1, 5% G2, 6% G3), median patient-reported neuropathy scores remained stable for at least 15 cycles. We report the first prospective data on treatment with 1st line Eribulin in elderly pts. A reduced starting dose of 1.1 mg/m2 is safe and the efficacy as expected, although the lower boundary of the 90% CI crossed the predefined threshold. A relevant subgroup of pts had prolonged disease control and tolerated this long time treatment without worsening of patient-reported neuropathy.