Dual HER2 Blockade Plus Ribociclib Offers Chemo-Free Option in HR+/HER2+ Breast Cancer

Breast cancer cells: © LASZLO- stock.adobe.com

In patients with HER2- and hormone receptor (HR)-positive metastatic breast cancer, chemotherapy-free treatment with dual HER2-targeted therapy, consisting of trastuzumab (Herceptin) and pertuzumab (Perjeta), plus endocrine therapy could be an effective alternative, and the addition of the CDK4/6 inhibitor ribociclib (Kisqali) may further improve survival outcomes.

These findings come from the second interim efficacy analysis of the phase 3 DETECT V trial (NCT02344472) 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 1 of 2 arms. In the chemotherapy arm, patients received physician’s choice of chemotherapy plus trastuzumab/pertuzumab followed by maintenance trastuzumab/pertuzumab and endocrine therapy. In the chemotherapy-free arm, patients received physician’s choice of endocrine therapy plus trastuzumab/pertuzumab. After 124 patients enrolled, the study was amended to add ribociclib to endocrine therapy in both arms.

Overall survival (OS) and progression-free survival (PFS) did not differ between the arms. In the chemotherapy-free arm, the median OS was not reached vs 46.1 months in the chemotherapy arm (HR, 1.03; 95% CI, 0.63-1.70; P =.907). For PFS, the median was 19.1 months in the chemotherapy-free arm vs 22.4 months in the chemotherapy arm (HR, 1.19; 95% CI, 0.84-1.69; P =.34).

However, the addition of ribociclib did improve OS and PFS in both arms, with HRs of 0.52 (95% CI, 0.37-0.75; P <.001) for PFS and 0.42 (95% CI, 0.24-0.74; P =.002) for OS.

Wolfgang Janni, MD, PhD, emphasized that this was a comparison of subsequent study cohorts, not a randomized comparison for the addition of ribociclib. Janni is a professor at the University of Ulm in Ulm, Germany.

Regarding safety of the chemotherapy vs chemotherapy-free arms, the most common adverse event (AE) in both arms was diarrhea, with 100 all-grade incidences in the chemotherapy-free arm and 146 in the chemotherapy arm.

Wolfgang Janni, MD

“We did observe a higher amount of diarrhea in the chemotherapy containing arm, while we saw more prolonged neutropenia in the chemo[therapy]-free arm, possibly due to longer exposure to ribociclib,” Janni explained. In the chemotherapy-free arm, there were 64 incidences of all-grade neutropenia and 48 grade 3 or higher.

For the safety analysis of ribociclib vs no ribociclib, 55 patients (37.4%) receiving ribociclib experienced at least 1 serious AE vs 43 patients (34.7%) in the no ribociclib arm (P =.640). Ninety-five patients (64.6%) and 62 patients (50.0%) in the ribociclib and no ribociclib arms, respectively, experienced at least 1 grade 3 or higher AE.

“The tolerability comparison between the 2 cohorts did not show a difference in the overall incidence of serious adverse events, but in adverse events with grade 3 or higher, which was mainly caused by the higher incidence of neutropenia and liver enzyme abnormalities in the ribociclib 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 ribociclib cohort, which had shorter follow-up due to its later addition into the study regimens.

REFERENCE:

Janni W, Fehm T, Müller V, et al. Omission of chemotherapy and addition of the CDK4/6 inhibitor ribociclib in HER2-positive and hormone-receptor positive metastatic breast cancer. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 350MO.