209P Trastuzumab plus lapatinib or chemotherapy in patients with HER2-positive advanced breast cancer refractory to anti-HER2 therapies: A randomized, multicenter, phase II trial (GIM12-TYPHER)

Trastuzumab (T) and chemotherapy (CT) is a standard treatment in patients (pts) with HER2-positive (+) advanced breast cancer (ABC) at later lines of therapy. Lapatinib (L) and T have proven to be active in the same setting. The present study evaluated the efficacy, toxicity and quality of life (QoL) of T+L versus T + physician’s choice CT in pts with HER2+ ABC pretreated with at least two lines of anti-HER2 treatment. In this open-label, multicenter, phase II trial, pts were randomly assigned 1:1 to receive either T+L with endocrine therapy at the physician’s discretion in case of hormone receptor positive ABC (arm A) or T+CT (arm B). The primary endpoint was the clinical benefit rate (CBR) and the secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life (QoL), and safety. Between 2015 and 2020, 59 pts were randomized and evaluated for the present analyses. After a median (m) follow-up of 57.5 months (mo), the CBR was 20.7% (95% CI 9.4-39.3) vs 26.7% (95% CI 13.1-44.9; P= 0.76), the mOS was 29.9 mo (95% CI 19.6-NE) vs 31.1 mo (95% CI 26.1-NE; hazard ratio [HR] 1.07, 95% CI 0.57-2.0; P=0.82) and mPFS was 3.6 mo (95% CI 3.0-5.3) vs 6.1 mo (95% CI 4.0-14.3; HR 0.63, 95% CI 0.37-1.37; P=0.08) in arm A vs arm B, respectively. Any grade (G) adverse events (AEs) occurred in 86.2% and 66.7% of pts in arm A and B, respectively. The incidence of G3-4 AEs was 24.1% and 13.3% in arm A and B, respectively. The impact on QoL significantly favored arm A (P=0.03).Table: 209PAEsOverall (N=59)Arm A (N=29)Arm B (N=30)Patients with at least one AE45 (76.3)25 (86.2)20 (66.7)Diarrhea14 (23.7)11 (37.9)3 (10)Fatigue13 (22)7 (24.1)6 (20)Abdominal pain7 (11.9)3 (10.3)4 (13.3)Anemia7 (11.9)4 (13.8)3 (10)Neutropenia5 (8.5)0 (0)5 (16.7)Nausea5 (8.5)3 (10.3)2 (6.7)Thrombocytopenia5 (8.5)4 (13.8)1 (3.3)Paresthesia4 (6.8)0 (0)4 (13.3)Fever3 (5.1)3 (10.3)0 (0)Skin disorders3 (5.1)3 (10.3)0 (0) Open table in a new tab No difference in efficacy was observed between T+L and T+CT. QoL deterioration was less frequent in pts in T+L arm though a higher number of any AEs was observed in these patients compared with those who received T+CT. Overall, the chemotherapy-free combination of T+L may be a valid therapeutic option for pretreated pts with HER2+ ABC.