Abstract P2-13-16: Dual HER2-blockade with pertuzumab (P) and trastuzumab (T) in patients with HER2-positive metastatic breast cancer (mBC) relapsing after adjuvant treatment with T. Results from a German non-interventional study (NIS) HELENA (NCT01777958)
Authors: Thill Marc ,   Lead Auth., Grafe Andrea , Klare Peter , Luedtke-Heckenkamp Kerstin , Reichert Dietmar , Wimberger Pauline , Zaiss Matthias , Ziegler-Loehr Katja , Eckl Tanja , Schneeweiss Andreas 
Published: March 2022

Abstract
Background: Treatment of HER2 overexpressing mBC with the HER2 directed antibody combination of P and T became standard of care since marketing authorization of P based on the results of the randomized controlled CLEOPATRA trial (NCT 00567190). NIS HELENA was designed to document effectiveness and safety in clinical routine of first-line palliative therapy with P plus T and docetaxel (D) in patients with advanced HER2-positive BC after adjuvant therapy with T, and to determine whether the median PFS of 16.9 months (mos) reported for this subgroup in the CLEOPATRA trial can also be observed in day-to-day routine. Methods: Between 06/2013 through 07/2016, 126 patients with in-label use of P at study start (full-analysis set, FAS) in 81 German hospital-based or outpatient study sites were included into this NIS. Intense documentation period of this NIS was limited to 28 therapy cycles, and a follow-up (FU) for a maximum of 24 mos. Safety was assessed in all patients with at least one dose of P (safety set, SAF, n=132 ). QoL was assessed by FACT-B questionnaire. Main parameter of interest was mPFS. Patient Characteristics: Mean age of FAS patients was 55.1 [30.7 - 80.2] years, 81.7% (95.2%) were below 65 (75) years of age. 51.6% of the FAS patients were hormone-receptor positive (HR+), 91.3% patients of the FAS had distant, 69.8% had visceral, 45.2% liver metastases (VM). 89.7% patients of the FAS had R0-resection, including 44% breast conserving surgery, 42.9% of the FAS received neoadjuvant and 61.9% adjuvant chemo-/immunotherapy and 62.7% prior endocrine treatment. For the FAS median disease-free interval was 40.2 [6.6 - 95.9] mos. Effectiveness results: mPFS of FAS was 18.8 [15.1; 24.2] mos, longest mPFS was documented in patients with non-VM (20.5 [17.7, 27.7] mos), patients &lt; 65 years (19.7 [15.4, 25.7] mos), and HR negative patients (19.4 [13.8, 27.7] mos). Overall response rate in the FAS was documented with 64.3% (55.6; 72.1], with best ORR in HR+ patients (69.2% [57.2, 79.1]), patients with VM (68.2%, [57.9, 77.0] and patients &lt; 65 years (65% [55.5, 73.6]). 46 patients (36.5%) died during the study. Median OS was 55.9 mos [41.2, not reached] for the FAS. Safety: 93.9% of the SAF had an adverse event (AE), 32.6% a serious AE (SAE). AEs related to P occurred in 53.8% of SAF, SAEs related to P were documented in 13.6%. Diarrhea was the most frequently reported related (S)AE. Fatal AEs were seen in 6.1% of the SAF, in 2 patients related to P (death, central nervous system metastases and cerebral disorder). AEs leading to treatment discontinuation of any study product were observed in 20.5% of the SAF. During the intense documentation period, 11 patients had a LVEF &lt;55%. QoL assessment using the total score index, increased slightly over time, however, based on declining patient response rates. Conclusion: Based on results from NIS HELENA, outcomes of pivotal CLEOPATRA study with respect to patients relapsing after adjuvant T pretreatment can be transferred into clinical routine. Patients derived benefit to a variable extent according to predefined subgroups. No new safety signals were detected.
Citation Format: Marc Thill, Lead Auth., Andrea Grafe, Peter Klare, Kerstin Luedtke-Heckenkamp, Dietmar Reichert, Pauline Wimberger, Matthias Zaiss, Katja Ziegler-Loehr, Tanja Eckl, Andreas Schneeweiss. Dual HER2-blockade with pertuzumab (P) and trastuzumab (T) in patients with HER2-positive metastatic breast cancer (mBC) relapsing after adjuvant treatment with T. Results from a German non-interventional study (NIS) HELENA (NCT01777958) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-16.