Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansine vs. lapatinib plus capecitabine in Chinese patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy

Abstract

Background: The antibody-drug conjugate (ADCs) trastuzumab emtansine (T-DM1) is approved for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. The phase III ELAINA trial aimed to determine the clinical utility of T-DM1 in Chinese patients.

Methods: ELAINA was a randomized, multicenter, open-label bridging study of Chinese patients with HER2-positive locally advanced breast cancer (LABC) or mBC previously treated with trastuzumab and a taxane. Using an interactive voice/internet response system, patients were randomized 3:1 to receive T-DM1 or lapatinib plus capecitabine. Patents were stratified by number of prior therapies in this disease setting and by presence of visceral disease using a permuted block randomization scheme. Patients received treatment until disease progression, unmanageable toxicity, or study termination. After that, data on survival and subsequent cancer therapies were collected at approximately 3-month intervals. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall response rate, duration of response, overall survival (OS), safety, patient-reported quality of life, and pharmacokinetics (PKs).

Results: ELAINA was fully enrolled with 200 patients randomized to T-DM1 (n=151) or lapatinib plus capecitabine (n=49). Median treatment duration was approximately 6 months in each study arm. Median follow-up time was approximately 9 months for all analyses except for OS. T-DM1 was associated with a 15% reduction in risk of disease progression or death compared with lapatinib plus capecitabine [stratified hazard ratio (HR) =0.85; 95% confidence interval (CI): 0.56-1.29] in the intent-to-treat (ITT) population. The objective response rate (ORR) was similar with T-DM1 (50.4%) and lapatinib plus capecitabine (55.8%); median duration of response was 8.4 months for both treatments. At a median follow-up time of approximately 30 months, OS was similar in each treatment arm. Incidence of grade ≥3 adverse events (AEs) was similar with T-DM1 (54.3%) and lapatinib plus capecitabine (57.1%). Grade ≥3 thrombocytopenia was greater with T-DM1 (40.4%) than with lapatinib plus capecitabine (4.1%); there was no grade ≥3 hemorrhage with either treatment.

Conclusions: T-DM1 demonstrated an acceptable benefit-risk profile in Chinese patients with HER2-positive LABC/mBC previously treated with trastuzumab and a taxane. T-DM1 therefore provides a chemotherapy-free option in this setting.

Trial registration: ClinicalTrials.gov identifier: NCT03084939.

Keywords: ELAINA bridging study; human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer; metastatic breast cancer (mBC); trastuzumab emtansine (T-DM1).

Figure 1

Patient disposition.

Figure 2

Progression-free survival. (A) Kaplan-Meier plot and (B) forest plot of clinically relevant subgroups; hazard ratios are unstratified. −, negative; +, positive; T-DM1, trastuzumab emtansine; PFS, progression-free survival; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hormone receptor; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; DDISH, dual-color dual-hapten in situ hybridization; NE, not evaluable.

Figure 3

Time to deterioration in HRQoL from baseline as defined by a ≥5-point decrease from baseline score in the FACT-B Trial Outcome Index. T-DM1, trastuzumab emtansine; HRQoL, health-related quality of life; FACT-B, Functional Assessment of Cancer Therapy-Breast.