Cardiac safety of the trastuzumab biosimilar ABP 980 in women with HER2-positive early breast cancer in the LILAC study.

Abstract

557 Background: Although trastuzumab is generally well-tolerated, cardiotoxicity is the main limitation in its use, leading to a severe heart failure in 2-4% of patients in adjuvant trials. In the phase 3 LILAC trial, trastuzumab biosimilar ABP 980 demonstrated similar efficacy, safety, and immunogenicity to trastuzumab reference product (RP) in women with HER2-positive early breast cancer. Here we report analyses comparing cardiac safety of ABP 980 and RP. Methods: In the neoadjuvant phase, all 725 patients received 4 cycles of chemotherapy with epirubicin + cyclophosphamide Q3W and were then randomized 1:1 to ABP 980 (n = 364) or RP (n = 361) with a loading dose of 8 mg/kg, then 6 mg/kg IV Q3W for 3 cycles plus paclitaxel Q3W (4 cycles) or QW (12 cycles). After surgery, patients received investigational product (IP) Q3W for up to 1 year; ABP 980-treated patients continued ABP 980, and RP-treated patients either continued RP (n = 190) or switched to ABP 980 (RP/ABP 980; n = 171). AEs were assessed every 3 weeks and cardiac safety every 3 months. Cardiac safety was monitored by computerized 12-lead ECG; LVEF was assessed by 2D ECHO. LVEF decline was defined as LVEF value decrease from study baseline by ≥10 percentage points and to < 50%. Results: Treatment groups were well balanced with regard to IP disposition. Over the entire study, 22 (3.1%) patients had LVEF decline by ≥10 percentage points compared to baseline and to < 50%; no meaningful between-group differences were observed (ABP 980:10/359 [2.8%], RP: 6/184 [3.3%], RP/ABP 980: 6/171 [3.5%]). The incidence of cardiac AEs was low and comparable in treatment groups. One grade 3 cardiac failure event was reported in the RP/ABP 980 arm; another in the RP arm was coincident with LVEF decline. No patient discontinued IP during adjuvant phase because of cardiac failure. Conclusions: These pre-specified analyses confirm the tolerability of ABP 980 and demonstrate clinical similarity of ABP 980 and RP with respect to cardiac safety. The incidence of LVEF decline was consistent with the known cardiac safety profile of the RP. No new cardiac safety signals were observed whether patients were on ABP 980 or switched from RP to ABP 980. Clinical trial information: NCT01901146.

Safety and efficacy comparisons of intravenous trastuzumab biosimilars to the reference product medicine in treatment‐naïve and switch‐over patients with breast cancer: a systematic and meta‐analysis

“…Among all included studies, seven reported on ABP 980, 12,22–24,28–30 two on BCD‐022, 11,27 seven on CT‐P6, 31–34,43–45 two on HD201, 14,50 five on HLX02, 15–17,48,49 four on MYL‐1401O, 51–54 five on PF‐05280014, 13,25,26,46,47 eight on SB3, 35–42 and one on Trasturel 21 . All studies contained data in treatment‐naïve patients, and seven studies 12,22–24,28–30 reported data on switching patients; however, these data were obtained from a single studied population, so these data points were collated. The outcomes of included studies 11–17,21–33,35–53,54 are summarised in Table 2.…”

“…Overall, nine brands of trastuzumab (BCD-022, ABP980, SB3, CT-P6, PF-05280014, HD201, TrastuRel, MYL-1401O, HLX02) were examined (Table 1). All studies on trastuzumab were conducted with either paclitaxel [11][12][13][14][21][22][23][24][25][26][27][28][29][30] or docetaxel (with 5 fluorouracil epirubicin cyclophosphamide (FEC) [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] or carboplatin, 46,47 or as monotherapy [15][16][17]48,49 ) or 'taxane' [50][51][52][53][54] (Table 2). One study, by Apsangikar et al, was conducted independently, 21 while all other studies were funded by the innovator company or by an unknown source.…”

“…Forty-one studies reporting on RCTs were identified and included in the analysis, with 34 studies reporting efficacy outcomes (Table 1). Among all included studies, seven reported on ABP 980, 12,[22][23][24][28][29][30] two on BCD-022, 11,27 seven on CT-P6, [31][32][33][34][43][44][45] two on HD201, 14,50 five on HLX02, [15][16][17]48,49 four on MYL-1401O, [51][52][53][54] five on PF-05280014, 13,25,26,46,47 eight on SB3, [35][36][37][38][39][40][41][42] and one on Trasturel. 21 All studies contained data in treatment-na€ ıve patients, and seven studies 12,[22][23][24][28][29]…”

“…21 All studies contained data in treatment-na€ ıve patients, and seven studies 12,[22][23][24][28][29][30] reported data on switching patients; however, these data were obtained from a single studied population, so these data points were collated. The outcomes of included studies [11][12][13][14][15][16][17][21][22][23][24][25][26][27][28][29][30][31][32][33][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]54 are summarised in Table 2.…”

Clinical and treatment characteristics of patients treated with the first therapeutic oncology biosimilars bevacizumab-awwb and trastuzumab-anns in the US

“…Approval was granted for the full range of indications of the originator product via extrapolation of efficacy and safety data from the 'totality of evidence'. [16][17][18][19][20] The market entry of biosimilars provides more affordable treatment options for patients with cancer. 21 Significant cost-savings resulting from biosimilar use has been reported in European countries, [22][23][24] and the projected cost-savings over the next 5 years from biosimilar usage is estimated to be over $100 billion in the US market.…”