ELEANOR, IMpassion132, and targeted combination for mBC

ELEANOR: Diarrhoea manageable in real-world study of neratinib in EBC

By Elizabeth Donald

Professor Rupert Bartsch explains what the ELEANOR findings mean for managing the risk of diarrhoea in patients taking neratinib. View transcript

Interim results from the ELEANOR study, presented by Rupert Bartsch (Medizinische Universitaet Wien, Vienna, Austria) and colleagues, highlight the real-world safety profile of neratinib for patients with HER2-positive early breast cancer (EBC). Neratinib, approved in Europe for extended adjuvant treatment of HER2+/hormone receptor-positive EBC, showed promising outcomes when assessed over 5 years in the ExteNET study, significantly improving invasive disease-free survival.

In this interim report of 286 participants in the ELEANOR study, serious treatment-emergent adverse events (TEAEs) were reported in 5.9% of the study population, with the most common TEAEs being diarrhoea (81.3%), nausea (22.2%), and fatigue (19.8%). Grade 3 or higher TEAEs were noted in 26% of patients, but there were no fatal events. The proportion of people with grade 3 diarrhoea was lower in the ELEANOR study compared with the ExteNET study (20.1% vs 39%). This reduction was attributed to the increased use of prophylactic diarrhoea treatment in ELEANOR (given to 86.8% of study participants) and a lower starting dose (<240 mg/day) of neratinib with planned dose escalation. Consequently, diarrhoea led to treatment discontinuation in 10.8% of patients.

Overall, the study confirms neratinib’s favourable safety profile and illustrates effective management of adverse events, particularly diarrhoea, through dose escalation and increased awareness. The findings support the continued use of neratinib post-adjuvant T-DM1 and dual HER2-blockade with pertuzumab and trastuzumab in the real-world clinical setting. The median treatment duration was 11.9 months, reinforcing neratinib's long-term tolerability and adherence in managing HER2-positive EBC.

Professor Bartsch explains how he communicates with patients about diarrhoea risk and manages the side effect in his clinic. View transcript

IMpassion132 results: ICIs in early-relapsing triple-negative breast cancer

Rebecca Dent's (National Cancer Centre, Singapore) presentation focused on the use of immune checkpoint inhibitors (ICIs) in early-relapsing triple-negative breast cancer (aTNBC). The IMpassion132 trial (NCT03371017) studied patients relapsing within 12 months after anthracycline- and taxane-containing adjuvant chemotherapy or primary TNBC surgery.

Initially enrolling patients regardless of PD-L1 status, the protocol was later amended to enrich for PD-L1+ tumours. A total of 572 patients were randomised to receive placebo or atezolizumab with chosen chemotherapy until progression. The primary endpoint of overall survival (OS) was not met, with a median OS of approximately 11.2 months in the placebo group and 12.1 months in the atezolizumab group. Progression-free survival (PFS) was similar between arms, and objective response rates (ORR) favoured the atezolizumab group (28% vs 40%). Adverse events were comparable between groups, and were mostly haematological.

Patients with early-relapsing aTNBC in IMpassion132 did not benefit from atezolizumab, highlighting the need for a better understanding of intrinsic resistance to ICIs in this population for future trial design

Professor Michael Gnant outlines his congress highlights, including data from the IMpassion 132, NATALEE and PANTHER trials. View transcript

Novel therapy offers promising results in metastatic breast cancer

Séverine Guiu (Montpellier Cancer Institute, France) presented data on the efficacy of a novel treatment approach for metastatic breast cancer (mBC) targeting specific molecular abnormalities. The study focused on patients with ER+/HER2– mBC and identified those with somatic or germline pathogenic variants (PV) in genes related to homologous recombination repair (HRR) or with microsatellite instability. The combination therapy consisted of olaparib, durvalumab and fulvestrant, and patients had previously received endocrine therapy and chemotherapy.

The results were promising, with a PFS rate at 24 weeks of 66% in the overall group and 76% in patients with germline BRCA1/2 mutations (gBRCAm). The median PFS was 9.3 months for the whole cohort (N=172), 12.6 months for patients with gBRCAm (n=72), and 9.0 months for patients with non-gBRCAm (n=100). The ORR was 41%, and the median OS was 30 months.

Adverse events (AEs) were manageable, with the most common being nausea and asthenia. Around a third of patients experienced grade 3 AEs, with anaemia being the most frequent. Despite these AEs, the combination therapy did not lead to treatment discontinuation in the majority of patients.

The combination of olaparib, durvalumab and fulvestrant could be an effective second- to third-line treatment option for patients with ER+/HER2– mBC and specific molecular abnormalities