Tucatinib/tucatinib combination shows meaningful activity in HER2+ metastatic breast cancer

Based on the 2nd SGNTUC-19 basket trial (NCT04579380) results, tucatinib/tucatinib(Tucatinib vs. trastuzumab (Trastuzumab) in a small group Demonstrated clinically meaningful antitumor activity and durable responses in heavily pretreated patients with HER2-mutated metastatic breast cancer who were HER2-negative on local testing.

Data from this study showed that among patients evaluable for efficacy analysis (n=31), the confirmed objective response rate (ORR) of the combination regimen was 41.9% (n=13; 90%CI, 26.9%-58.2%), of which 2 (6.5%) patients achieved complete response (CR) and 11 (35.5%) patients achieved partial response (PR). Additionally, the disease control rate (DCR) was 80.6% (n=25; 90% CI, 65.3%-91.2%), with 12 patients (38.7%) reported to have stable disease. The median duration of response (DOR) in this patient population was 12.6 months (90% CI, 4.7-not estimable [NE]).

Other efficacy data showed that the median progression-free survival (PFS) of patients treated with the combination regimen was 9.5 months (90% CI, 5.4-13.8). Additionally, the median overall survival (OS) in this patient group was 20.1 months (90% CI, 15.9-NE). In the SGNTUC-19 study, tucatinib and trastuzumab (in combination with fulvestrant in patients with HR-positive disease) were active in heavily pretreated patients with HER2-mutated metastatic breast cancer, with a confirmed ORR of 41.9%.

Open labelThe phase 2 basket trial enrolled patients with previously treated locally advanced, unresectable, or metastatic HER2mutated solid tumors. The cancer cohort included patients withoutevidence of HER2 overexpression or amplification. To be eligible for treatment, patients with locally advanced or metastatic disease must have progressed on at least one prior line of therapy and must have progressed on or been intolerant to the most recent systemic therapy. Patients with HR-positive disease must receive CDK4/6 inhibitor therapy in the metastatic setting.

Patients in the metastatic breast cancer cohort (n=31) received 300 mg oral tucatinib twice daily plus 8 mg/kg intravenous trastuzumab, then 6 mg/kg every 3 weeks for 21 days. In addition, patients with HR-positive disease received 500 mg of fulvestrant intramuscularly every 4 weeks starting in Cycle 1 on Day 1 and Day 15 of Cycle 1. The primary efficacy endpoint is ORR. Secondary endpoints included DCR, DOR, PFS, OS, maximum and trough tucatinib concentrations, and safety.

Safety results showed that treatment-emergent adverse events (TEAEs) of any grade were observed in all evaluable patients (n=31; 100%), with 15 (48%) patients experiencing at least 1 TRAE of grade 3 or higher. The most common TRAEs of any grade included diarrhea, nausea, vomiting, pruritus, and infusion-related reactions. The most common grade 3 or higher TRAEs include diarrhea, increased alanine aminotransferase, hypertension, back pain, decreased appetite, and increased aspartate aminotransferase.

NoneTEAEs led to discontinuation of all study treatments, and 2 patients had TEAEs that led to discontinuation of tucatinib; aspartate aminotransferase elevation was grade 4 and pseudocirrhosis was grade 2. There were no TEAE-related discontinuations of trastuzumab or fulvestrant. TEAEs resulted in tucatinib dose reductions in 7 patients and 1 patient. No TEAEs were associated with death, and all 11 deaths were due to disease progression.

Reference materials:https://www.cancernetwork.com/view/tucatinib-combo-shows-meaningful-activity-in-her2-metastatic-breast-cancer