A randomized, open-label, Phase III trial of pertuzumab retreatment in HER2-positive locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab and chemotherapy: the Japan Breast Cancer Research Group-M05 PRECIOUS study

Abstract

The PRECIOUS study (UMIN000018202) is being conducted as a multicenter, randomized, open-label Phase III study to determine if retreatment with pertuzumab is more effective than conventional treatment in HER2-positive locally advanced (LA)/metastatic breast cancer (MBC) patients previously treated with pertuzumab, trastuzumab and chemotherapy. Patients are randomized 1:1 into chemotherapy plus trastuzumab with or without pertuzumab groups. The latest regimen before enrollment did not include pertuzumab, and the number of previous chemotherapy regimens for LA/MBC did not exceed three. The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include independent reviewer-assessed progression-free survival, progression-free survival in patients treated with trastuzumab emtansine as the latest regimen, response rate, response duration, overall survival, safety and health-related quality of life. Target accrual is 370 patients, allowing the observation of 325 events, yielding an 80% power for detection of a hazard ratio of 0.739 with a one-sided 5% level of significance.

Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation

“…This clinical study aims to demonstrate the usefulness of PER re-administration after resistance to T-DM1 in HER2-positive locally advanced/metastatic breast cancer patients with a history of PER administration. This study is based on the premise that if HER2–HER3 signaling, which was suppressed by previously used PER-containing regimens, is restored during anti-HER2 therapy without PER, such as T-DM1 therapy before re-administration of a PER-containing regimen, PER re-administration might potentially re-suppress HER2–HER3 signaling [ 34 ]. If the efficacy of PER re-administration is demonstrated in the PRECIOUS trial, then PER re-administration may become the standard third- and subsequent-line therapy for HER2-positive locally advanced/metastatic breast cancer.…”

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

“…OS tends to be better in pertuzumab rechallenge group, though evaluation in a prospective study is necessary. The results of an ongoing multicentre randomized phase-three study examining the effect of pertuzumab rechallenge are awaited (PRECIOUS study: UMIN000018202) [21]. For the above two points, we are planning additional post hoc analysis using the propensity score matching method.…”

Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive advanced breast cancer

“…Additionally, T-DM1 efficacy has been suggested to be reduced in patients who received pertuzumab-trastuzumab in the previous line compared with those who received trastuzumab alone [61,62]. However, a phase III trial of pertuzumab retreatment (PRECIOUS; NCT02514681) has shown that pertuzumab-trastuzumab plus chemotherapy retreatment in third or fourth line is feasible [63]. Currently, switching to T-DXd is the preferred option for patients previously treated with trastuzumab plus taxane [31] and after T-DM1 [33].…”