Combining tucatinib with ado-trastuzumab emtansine does not appear to result in any new safety signals in the treatment of those with locally advanced or metastatic HER2-positive breast cancer.
Tucatinib (Tukysa) in combination with ado-trastuzumab emtansine (T-DM1; Kadcyla) resulted in an improvement in progression-free survival (PFS) for those with unresectable locally advanced or metastatic, HER2-positive breast cancer previously treated with a taxane plus trastuzumab (Herceptin), according to a press release on findings from the phase 3 HER2CLIMB-02 trial (NCT03975647).1
This PFS benefit met the trial’s primary end point. Investigators also reported that the overall survival (OS) data were immature at the time of the press release. Additionally, rates of treatment discontinuation due to adverse effects (AEs) were higher among patients receiving tucatinib plus T-DM1 compared with those receiving T-DM1 alone, although the combination therapy did not raise any new safety signals.
“We are encouraged by these results for [tucatinib] in combination with [T-DM1] in metastatic HER2-positive breast cancer, including in patients with brain metastases,” Roger Dansey, president of Research and Development and chief medical officer at Seagen Inc., said in the press release. “We plan to present the HER2CLIMB-02 [trial] data at an upcoming medical meeting and discuss the results with the FDA.”
In the international, multi-center, double-blind, randomized phase 3 HER2CLIMB-02 trial, patients were randomly assigned to receive 300 mg of oral tucatinib twice a day or matched placebo plus 3.6 mg/kg of T-DM1 intravenously every 21 days.
The trial’s primary end point was PFS based on investigator assessment per RECIST v1.1 criteria. Secondary end points included OS, PFS based on blinded independent committee review assessment, objective response rate, duration of response, clinical benefit rate, PFS and OS in those with brain metastases at baseline, and AEs.
Patients 18 years and older with histologically confirmed HER2-positive breast carcinoma and prior treatment with a taxane and trastuzumab in any setting were able to enroll on the trial. Additional eligibility criteria included having measurable or non-measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1. Patients also needed to have no evidence of brain metastases, untreated brain metastases not requiring immediate local therapy, or previously treated brain metastases to enroll on the trial.
Patients who received prior treatment with tucatinib, afatinib (Gilotrif), fam-trastuzumab deruxtecan-nxki (Enhertu), or any other investigational anti-HER2 or anti-EGFR therapy were unable to enroll on the trial. Having any untreated brain lesions more than 2 cm in size, ongoing use of corticosteroids to control brain metastases at a daily dose of more than 2 mg of dexamethasone, any brain lesion requiring immediate local therapy, or known or concurrent leptomeningeal disease was also grounds for exclusion.
The FDA approved tucatinib plus trastuzumab and capecitabine (Xeloda) for treating adult patients with advanced HER2-positive breast cancer who have received 1 or more prior lines of therapy in April 2020.2 Supporting data for this approval came from the phase 2 HER2CLIMB trial (NCT02614794), in which the tucatinib-based regimen yielded a median PFS of 7.8 months (95% CI, 7.5-9.6) vs 5.6 months (95% CI, 4.2-7.1) with placebo plus trastuzumab and capecitabine (HR, 0.54; 95% CI, 0.42-0.71; P <.00001). The median PFS for patients with baseline brain metastases was 7.6 months (95% CI, 6.2-9.5) vs 5.4 months (95% CI, 4.1-5.7) in each respective arm (HR, 0.48; 95% CI, 0.34-0.69; P <.00001).