Trastuzumab emtansine in the treatment of HER2-positive metastatic breast cancer in Japanese patients

Figures & data

Table 1 Pharmacokinetic parameters of T-DM1 at 3.6 mg/kg

Trial name	Mean (SD)
	AUCinf (day μg/mL)	t1/2 (day)	Vss (mL/kg)	Clearance (mL/day/kg)
JO22591^Citation8 (n=5)	346 (41.1)	3.74 (1.15)	59.1 (6.62)	10.6 (1.26)
JO22997^Citation4 (n=31)	365 (68)	3.62 (0.78)	54.9 (13.9)	10.3 (2.30)
TDM4258g^Citation10,Citation15 (n=101)	457 (129)	3.52 (0.71)	28.4 (12.9)	8.51 (2.69)
TDM4374g^Citation15 (n=105)	486 (141)	3.96 (0.96)	31.2 (10.9)	8.04 (2.97)

Abbreviations: AUC_inf, area under the concentration-time curve from time 0 extrapolated to infinity; t_1/2, half-life; V_ss, volume of distribution at steady state; SD, standard deviation; T-DMI, trastuzumab emtansine.

Table 2 Efficacy of T-DM1 as monotherapy

Trial name	Phase	n	Treatment setting	ORR (%)	PFS (months)	Reference
JO22997	II	73	Second-line	38.4 (90% CI 28.8–48.6)	5.6 (95% CI 4.6–8.2)	Masuda et al^Citation11
TDM4258g	II	112	Second-line	25.9 (95% CI 18.4–34.4)	4.6 (95% CI 3.9–8.6)	Burris et al^Citation10
TDM4374g	II	110	Second-line	34.5 (95% CI 26.1–43.9)	6.9 (95% CI 4.2–8.4)	Krop et al^Citation12
TDM4450g	II (randomized)	67	First-line	64.2 (95% CI 51.8–74.8)	14.2	Hurvitz et al^Citation23
EMILIA	III	495	Second-line	43.6 (95% CI 38.6–48.6)	9.4	Verma et al^Citation7

Abbreviations: CI, confidence interval; PFS, progression-free survival; ORR, objective response rate; T-DMI, trastuzumab emtansine; EMILA, A Randomized, Multicenter, Phase III Open-label Study of the Efficacy and Safety of Trastuzumab Emtansine vs. Capecitabine + Lapatinib in Patients with HER2-positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-based Therapy.

Table 3 Phase III studies of T-DM1

Trial name	Standard arm	Experimental arm	Treatment setting	Target number (total)
MARIANNE^Citation18,* (NCT01120184)	Trastuzumab + taxane (docetaxel or paclitaxel)	T-DM1 + pertuzumab T-DM1 + pertuzumab placebo	MBC; first-line	1,095
TH3RESA^Citation20 (NCT01419197)	Treatment of physician’s choice	T-DM1	MBC; third-line	604
KAITLIN^Citation21,* (NCT01966471)	Trastuzumab + pertuzumab + taxane	T-DM1 + pertuzumab	Adjuvant therapy; following anthracyclines	2,500
KATHERINE^Citation23 (NCT01772472)	Trastuzumab	T-DM1	Adjuvant therapy; following preoperative therapy	1,484

Note:

* Japanese breast cancer patients participating.

Abbreviations: MBC, metastatic breast cancer; T-DMI, trastuzumab emtansine; MARIANNE, A Study of Trastuzumab-DM1 Plus Pertuzumab Versus Trastuzumab [Herceptin] Plus a Taxane in Patients With Metastatic Breast Cancer; TH3RESA, A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician’s Choice in Patients With HER2-Positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy; KAITLIN, A Study of Kadcyla (Trastuzumab Emtansine) Plus Perjeta (Pertuzumab) Following Anthracyclines in Comparison With Herceptin (Trastuzumab) Plus Perjeta and a Taxane Following Anthracyclines as Adjuvant Therapy in Patients With Operable HER2-positive Primary Breast Cancer; KATHERINE, A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients with HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy.

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