Guiseppe Curigliano, MD, discusses the design and results of the HER2CLIMB-02 study which evaluated the efficacy of tucatinib in combination with trastuzumab and capecitabine in HER2-positive breast cancer patients with and without brain metastases compared to placebo.
Guiseppe Curigliano, MD, an associate professor of Medical Oncology at the University of Milano and the head of the Division of Early Drug Development at the European Institute of Oncology, discusses the design and results of the HER2CLIMB-02 study (NCT03975647) which evaluated the efficacy of tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) in HER2-positive breast cancer patients (TKI) with and without brain metastases compared to placebo.
According to Curigliano, HER2CLIMB-02 took place after HER2Climb (NCT02614794). HER2CLIMB-02 allowed for crossover. During the study, patients received either the triple regimen or a placebo plus tucatinib.
The median duration of treatment for the experimental arm was 10 months and 6.1 months for the placebo arm. The overall survival (OS) for the experimental arm was 24.7 months compared to 19.2 months in the placebo arm. OS benefit was maintained even when control was put in for race, HER2-positivity, age, and brain metastases.
According to Curigliano, PFS was also longer for the experimental arm compared to the placebo arm. The PFS was 7.6 months in the experimental arm compared to the 4.9 months in the placebo arm. Adverse events were also found to be manageable.
0:08 | As you know very well, the protocol prespecified analysis has been presented at least 2 years after the last patient was randomized. And in the context of this presentation, we also had crossover from the placebo arm to receive tucatinib, trastuzumab, and capecitabine. The first patient crossover happened in February 2020. And the data cut off of this presentation has been updated to February 2021. A total of 410 patients have been included in tucatinib, trastuzumab, and capecitabine arm versus 202 patients in the placebo, trastuzumab, and capecitabine arm.
1:09 | The tucatinib/placebo duration of treatment was a mean over 10 months for tucatinib, trastuzumab, and capecitabine versus 6.1 months for placebo trastuzumab, and capecitabine.
Let's go now to define our results. With the longer follow-up, the median OS was 24.7 months in the tucatinib, trastuzumab, and capecitabine arm versus 19.2 months in the placebo, trastuzumab, and capecitabine arm. So, the OS benefit with tucatinib was mandated that with the longer follow-up with a 5.5-month improvement in median OS in the tucatinib arm compared to the placebo arm. The sensitivity analysis accounting for crossover shows with consistent results with intent to treat analysis. So, all the sub-populations derived with exactly the same OS benefit independently of age, less or more than 65 years old, race, white versus nonwhite, or more receptor status, positive versus negative, baseline brain metastases versus no, equal performance status, zero versus one, and region, North America versus the rest of the world.
3:11 | So, the OS in an exploratory analysis in patients with and without brain metastases, confirm the OS benefit that has been described in the previous analysis and that is confirmed with a longer follow up.
3:30 | Looking at the progression-free survival by investigator assessment, again, with a longer follow up, there is a confirmed progression-free survival benefit in the tucatinib, trastuzumab, and capecitabine arm versus placebo, trastuzumab, and capecitabine arm, that was confirmed to be 7.6 months in the tucatinib arm versus 4.9 months in the placebo arm.
4:00 | The rates of the most common adverse events remain stable with the longer follow-up. The most common toxicity was diarrhea, described as grade 3 in 53 patients, 13% of the patient population. And palmar-plantar erythrodysesthesia syndrome in 14% of the patients. In conclusion, the data of HER2CLIMB presented with the longer follow-up confirmed the OS benefit with tucatinib that was maintained with an additional 15.6 months of follow-up. With 5.5 months improvement in the median OS, the benefit was maintained at the crossover prespecified subgroup, and then improvement in OS was observed in patients with and without brain metastases. Tucatinib in combination with trastuzumab and capecitabine was well tolerated with the low rate of discontinuation and the safety profile was consistent with the primary safety analysis.