Treatment with Herceptin (trastuzumab) and Perjeta (pertuzumab) with endocrine therapy but without chemotherapy has been shown to potentially be an effective treatment for patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer. Furthermore, the addition of Kisqali (ribociclib) might improve patient outcomes even more.
These findings come from the second interim efficacy analysis of the phase 3 DETECT V trial presented at the 2024 ESMO Congress.
In the study, 270 patients with metastatic HR/HER2–positive breast cancer receiving a first to third line of treatment were randomized to one of two arms. In the chemotherapy arm, patients received physician’s choice of chemotherapy plus Herceptin/Perjeta followed by maintenance Herceptin/Perjeta and endocrine therapy. In the chemotherapy-free arm, patients received physician’s choice of endocrine therapy plus Herceptin/Perjeta. After 124 patients enrolled, the study was amended to add Kisqali to endocrine therapy in both arms.
Overall survival (OS, the time a patient lives, regardless of disease status) and progression-free survival (PFS, the time a patient lives without their disease spreading or worsening) was similar between the arms. In the chemotherapy-free arm, the median OS was not reached (meaning more than half of the patients in that arm were still alive) versus 46.1 months in the chemotherapy arm. For PFS, the median was 19.1 months in the chemotherapy-free arm versus 22.4 months in the chemotherapy arm.
The addition of Kisqali improved PFS and OS, with patients treated with Kisqali being 48% less likely to experience disease progression or death and being 58% less likely to die of any cause.
Dr. Wolfgang Janni emphasized that this was a comparison of subsequent study cohorts, not a randomized comparison for the addition of Kisqali. Janni is a professor at the University of Ulm in Ulm, Germany.
Regarding safety of the chemotherapy versus chemotherapy-free arms, the most common side effect in both arms was diarrhea, with 100 all-grade incidences in the chemotherapy-free arm and 146 in the chemotherapy arm.
“We did observe a higher amount of diarrhea in the chemotherapy containing arm, while we saw more prolonged neutropenia [low count of neutrophils, a type of white blood cell] in the chemo[therapy]-free arm, possibly due to longer exposure to [Kisqali],” Janni explained. In the chemotherapy-free arm, there were 64 incidences of all-grade neutropenia and 48 grade 3 (severe) or higher.
For the safety analysis of Kisqali versus no Kisqali, 55 patients (37.4%) receiving Kisqali experienced at least one serious side effect versus 43 patients (34.7%) in the no Kisqali arm. Ninety-five patients (64.6%) and 62 patients (50%) in the Kisqali and no Kisqali arms, respectively, experienced at least one grade 3 or higher side effect.
“The tolerability comparison between the two cohorts did not show a difference in the overall incidence of serious [side effects], but in [side effects] with grade 3 or higher, which was mainly caused by the higher incidence of neutropenia and liver enzyme abnormalities in the [Kisqali] cohort. There were no treatment-associated deaths in this study,” Janni said.
The final results from this study are pending, as are longer-term findings from the Kisqali cohort, which had shorter follow-up due to its later addition into the study regimens.
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