Abstract P2-01-01: Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine
Authors: Bartsch Rupert , Harbeck Nadia , Wrobel Denise , Zaiss Matthias , Terhaag Jürgen , Guth Dagmar , Distelrath Andrea , Wuerstlein Rachel , Zahn Mark-Oliver , Lüftner Diana , Schwitter Michael , Balic Marija , Jackisch Christian , Müller Volkmar , Rinnerthaler Gabriel , Schmidt Marcus , Zaman Khalil , Schinköthe Timo , Resch Anna , Breitenstein Urs 
Published: March 2023

Abstract
Background Recent advances in the treatment of human epidermal growth factor receptor positive (HER2+) early breast cancer (eBC) have led to a reduction in recurrence risk; still a relevant percentage of patients relapses over time, predominantly presenting with distant recurrence. Neratinib is registered in Europe as extended adjuvant treatment for adult patients with HER2+, hormone receptor positive (HR+) eBC, who completed adjuvant trastuzumab-based therapy within one year prior to start of neratinib. In the ExteNET study, neratinib improved the absolute 5-year invasive disease-free survival (iDFS) rate by 5.1% versus placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]), mainly by reducing the rate of distant metastases. According to explorative analyses from ExteNET, the effect may be even more pronounced in patients with non-pCR after neoadjuvant trastuzumab treatment and/or in patients completing the full duration of neratinib therapy (i.e. ≥11 months of neratinib treatment). Diarrhea, the most common grade 3 adverse event (neratinib: 39% without primary diarrhea prophylaxis, median cumulative duration 5 days; placebo: 1%; no grade 4 events) can generally be managed through adequate prophylaxis and treatment management. ELEANOR is the first non-interventional study (NIS) of real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland. Methods Enrollment of 300 adult female patients with HER2+/HR+ eBC is planned in accordance with the SmPC specifications. Primary endpoint is the rate of patients adherent to neratinib treatment (i.e. neratinib use for ≥75% of treatment days). Secondary objectives include characterization of patients scheduled to receive neratinib, details on neratinib treatment, recurrences, safety/tolerability, and health-related quality of life (HRQoL). CANKADO, an eHealth application developed to support patient/physician communication, is an integral part of the NIS. Here, we report results of the preplanned interim analysis based on 200 enrolled patients. Results At data cut-off (May 2022), 202 patients had been observed for 3 months; patient enrollment is ongoing. Median age was 53.0 years and 66.3% of patients were at increased risk of disease recurrence (defined as non-pCR or AJCC stage &gt; I). Most patients had received prior neoadjuvant treatment (79.7%). Post-neoadjuvant treatment included dual HER2 blockade with trastuzumab and pertuzumab (38.8%/23.9% of pCR/non-pCR patients) and trastuzumab-emtansine (T-DM1, 53.5% of non-pCR patients). Neratinib treatment had been documented for 187 patients, treatment was ongoing for 46.0% of patients. Diarrhea was the most common adverse event (78.6% any grade, 19.3% grade 3, 2 patients grade 4), but was markedly lower when indirectly compared to ExteNET (39% grade 3). The neratinib dose escalation schedule was chosen for 36.4% of patients and led to a decreased incidence of severe diarrhea (16.2% grade 3, no grade 4 events). 93.9% (95% CI: 87.9-97.5%) of 115 evaluable patients adhered to neratinib treatment. Conclusion The results of this preplanned interim analysis reflect the current treatment landscape in Germany, Austria and Switzerland. These results confirm, in line with the observed adherence data, that extended adjuvant neratinib use is feasible in typical clinical practice settings. Furthermore, treatment management strategies such as diarrhea prophylaxis or neratinib dose escalation are routinely used and can increase treatment tolerability markedly. The study is funded by Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).
Citation Format: Rupert Bartsch, Nadia Harbeck, Denise Wrobel, Matthias Zaiss, Jürgen Terhaag, Dagmar Guth, Andrea Distelrath, Rachel Wuerstlein, Mark-Oliver Zahn, Diana Lüftner, Michael Schwitter, Marija Balic, Christian Jackisch, Volkmar Müller, Gabriel Rinnerthaler, Marcus Schmidt, Khalil Zaman, Timo Schinköthe, Anna Resch, Urs Breitenstein. Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-01.