Double-blind, randomized, parallel group, phase III study to demonstrate equivalent efficacy and comparable safety of CT-P6 and trastuzumab, both in combination with paclitaxel, in patients with metastatic breast cancer (MBC) as first-line treatment.

Abstract

629 Background: CT-P6(C) is an anti-HER2 MoAb, a biosimilar to trastuzumab (T). This trial is a global phase III study to compare C with T, both in combination with paclitaxel (P) as first-line treatment in women with HER2+ MBC. Methods: 475 patients with centrally confirmed HER2+ MBC were randomized to receive either C+P (n=244) or T+P (n=231). Patients had to have a baseline LVEF ≥50% and no history of serious cardiac disease. Study medication was as follows: C or T 8 mg/kg i.v. (day 1), followed by 3-weekly C or T 6 mg/kg. P (175 mg/m23-weekly) was co-administered. The primary endpoint was overall response rate (ORR) as determined by independent review. Pooled analysis with data from phase I/IIb (NCT01084863) and III studies (NCT01084876) was predefined and endorsed by the EMA. Patient safety was monitored throughout the study by an independent data monitoring committee. Treatment was continued until disease progression, death or patient’s withdrawal. Results: In the pooled ITT population, ORR was 57% for C+P and 62% for T+P (difference: 5%; 95% CI: -0.14, 0.04) during the first 8 cycles of treatment. The limits of the 95% CIs for the difference in the proportions of responders were contained within the pre-defined range [-0.15, 0.15] required for equivalence. Median time to progression and median time to response were 11.07 vs. 12.52 months (P =0.10), and 1.38 vs. 1.38 months (P =0.37) for C+P and T+P, respectively. Frequency of treatment-related AEs is shown in the Table. Conclusions: Equivalence of C and T was observed for ORR in patients with HER2+ MBC in combination with P as first-line therapy. Secondary efficacy endpoints also supported the comparability between C and T. C was well tolerated with a safety profile comparable to that of T. Clinical trial information: NCT01084876. [Table: see text]

The Global Need for a Trastuzumab Biosimilar for Patients With HER2-Positive Breast Cancer

“…99 Published data from a study in patients with HER2 þ MBC showed comparability between CT-P6 and trastuzumab, each treatment in combination with paclitaxel, with respect to ORR and the incidence of adverse events. 86 Results from a trial comparing the efficacy of Hercules/Myl-1401O versus trastuzumab, each in combination with paclitaxel or docetaxel, as first-line treatment in patients with HER2 þ MBC showed equivalence in efficacy and comparable safety (Table 3). 89 Reported 24-week ORR was 69.6% (160 patients) in the Hercules/Myl-1401O group and 64.0% (146 patients) in the trastuzumab group, and the incidence of patients with at least 1 treatment-emergent adverse event was 96.8% (239 patients) in the Hercules/Myl-1401O group and 94.7% (233 patients) in the trastuzumab group.…”

Totality of Scientific Evidence in the Development of ABP 980, a Biosimilar to Trastuzumab

“…Four other biosimilars (CT-P6, MYL-1401O, SB3, and PF-05280014) have been approved by the FDA and EMA and have been shown to be similar to trastuzumab RP in confirmatory clinical studies (Table 3) [26,[33][34][35][36][37][38]. While all four biosimilars were evaluated with the recommended equivalence trial design, the patient population and primary endpoints in these studies differed from those used in the ABP 980 studies.…”

“…In these five trials, anthracycline/taxanebased chemotherapy was used in the neoadjuvant setting and taxane-based chemotherapy in the metastatic setting; no significant differences between the biosimilar trastuzumab and the trastuzumab RP were reported. The trials evaluating MYL-1401O, PF-05280014, and CT-P6 were conducted in HER2-overexpressing MBC; the primary endpoint in all three trials was ORR (the prespecified equivalence margin was ± 15%) [33,35,37]. As discussed earlier, MBC is a less sensitive and less homogenous population to demonstrate clinical equivalence of a biosimilar trastuzumab, and ORR is not the preferred primary endpoint since it is associated with a larger uncertainty in long-term efficacy outcomes.…”

“…It is thought that biosimilars may provide better overall value by offering additional treatment options. A few [26] Neoadjuvant and adjuvant EBC pCR CT-P6 (Herzuma ® ; trastuzumab-pkrb) [33,34] MBC Neoadjuvant EBC ORR ORR MYL-1401O (Ogivri ® ; trastuzumab-dkst) [35] MBC ORR SB3 (Ontruzant ® ; trastuzumab-pkrb) [36] Neoadjuvant EBC pCR PF-05280014 (Trazimera™; trastuzumab-qyyp) [37,38] MBC Neoadjuvant EBC ORR pCR considerations that would help realize the value of biosimilars include quality, sustainability, and reliability of supply without disruptions or shortages [41]. Given the grave impact of oncology drug shortages, including increased burden of time to deal with the shortage and potentially increased drug costs and, in some cases, elevated risk of medication errors, a reliable supply of high-quality biosimilars is critical for pharmacy operations and delivery of patient care [42].…”

Development of biosimilars in an era of oncologic drug shortages

“… 50 The potential biosimilar mAb CT-P6 (Celltrion) has demonstrated similarity to trastuzumab in pharmacokinetic and safety profile analyses, and comparable response rates in patients with HER2-overexpressing metastatic breast cancer in combination with paclitaxel. 52 …”