Ado-trastuzumab emtansine offers effective, tolerable option for breast cancer subtype
CHICAGO – Safety outcomes with first-line ado-trastuzumab emtansine in the final descriptive analysis of the MARIANNE trial appear similar to results seen in earlier phases of the trial and prior studies of the agent, according to results presented at the ASCO Annual Meeting.
The MARIANNE trial enrolled 1,095 patients with HER-2-positive advanced breast cancer who had not received chemotherapy. Patients were classified according to world region, visceral disease and initial treatment.
Participants were randomly assigned to first-line treatment with trastuzumab (Herceptin, Genentech) plus docetaxel or paclitaxel (n = 365), ado-trastuzumab emtansine (Kadcyla, Genentech) plus placebo (n = 367) or ado-trastuzumab emtansine plus pertuzumab (Perjeta, Genentech; n = 363). PFS by independent review facility served as the primary endpoint, with assessments of non-inferiority and superiority. Secondary endpoints included OS, PFS by investigator, ORR, safety and patient-related outcomes.
In the primary analysis, treatment that included ado-trastuzumab emtansine demonstrated non-inferior, but not superior, PFS relative to trastuzumab plus docetaxel or paclitaxel; median OS was not attained in any treatment arm. Participants who received treatment that included ado-trastuzumab emtansine also achieved longer gains in health-related quality of life in the primary analysis.
The final OS analysis presented at ASCO was completed after an estimated 20 months of continued follow-up, for a median follow-up duration of 54 months. That analysis included 353 patients treated with trastuzumab plus docetaxel or paclitaxel, 361 patients treated with ado-trastuzumab emtansine plus placebo and 366 patients treated with ado-trastuzumab emtansine plus pertuzumab.
The median age of patients was 55 years (range, 22-88) in the trastuzumab plus docetaxel or paclitaxel arm, 52 (range, 27-82) in the ado-trastuzumab emtansine plus placebo arm and 52 (range, 27-86) in the ado-trastuzumab emtansine plus pertuzumab arm. An ECOG performance status of 0 was more common than an ECOG performance status of 1 in all treatment arms (67% vs. 33% in the trastuzumab plus docetaxel or paclitaxel arm; 65% vs. 35% in the ado-trastuzumab emtansine plus placebo arm; and 65% vs. 35% in the ado-trastuzumab emtansine plus pertuzumab arm). Nearly half of the patients in all treatment arms had never received neoadjuvant therapy (44% in the trastuzumab plus docetaxel or paclitaxel arm; 45% in the ado-trastuzumab emtansine plus placebo arm; and 44% in the ado-trastuzumab emtansine plus pertuzumab arm).
Median OS was 50.9 months in the trastuzumab plus docetaxel or paclitaxel arm, 53.7 months in the ado-trastuzumab emtansine plus placebo arm and 51.8 months in the ado-trastuzumab emtansine plus pertuzumab arm. A sensitivity analysis allowed patients in the trastuzumab plus docetaxel or paclitaxel arm to receive ado-trastuzumab emtansine and/or pertuzumab following disease progression (n = 85); this analysis, which was censored before the treatment switch, demonstrated comparable results.
Grade 3 to 5 adverse events occurred in 55.8% of patients in the trastuzumab plus docetaxel or paclitaxel arm, 47.1% of patients in the ado-trastuzumab emtansine plus placebo arm and 48.6% of patients in the ado-trastuzumab emtansine plus pertuzumab arm. The most common grade 3 to 5 adverse events included neutropenia, thrombocytopenia, anemia, hypertension and increased alanine aminotransferase. A total of 512 patients died over the course of the entire study.
These results demonstrate that ado-trastuzumab emtansine is “an effective and tolerable alternative first-line treatment” for patients with HER-2-positive metastatic breast cancer, according to the researchers. - by Julia Ernst, MS
Perez EA, et al. Abstract 1003. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Perez is employed by Roche/Genentech. She reports stock and other ownership interests in the company. Please see the full study for a list of all other authors’ relevant financial disclosures.