C. Jackisch (Offenbach, Germany)

Klinikum Offenbach GmbH

Author Of 2 Presentations

 On-Demand ePoster Display

46P - Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) plus chemotherapy in HER2-positive early breast cancer (EBC): Safety results from the adjuvant phase of the randomised, open-label, multicentre phase 3 (neo)adjuvant FeDeriCa study

Abstract

Background

In the primary analysis of the neoadjuvant phase of the FeDeriCa study (NCT03493854; Tan AR, et al. Lancet Oncol 2021), PH FDC SC cycle 7 P + H serum trough concentrations were non-inferior to intravenous (IV) P + H, with comparable total pathological complete response rates and safety profiles. We present updated descriptive safety data that span the adjuvant phase of the study, with an additional 12 months beyond the primary analysis.

Methods

Patients (pts) with HER2-positive operable, locally advanced or inflammatory stage II–IIIC BC and left ventricular ejection fraction (LVEF) ≥55% were randomised 1:1 to eight neoadjuvant chemotherapy cycles (investigator’s choice between two standard regimens) + P IV (loading dose 840 mg, maintenance 420 mg) + H IV (8 mg/kg → 6 mg/kg) or chemotherapy + PH FDC SC (1200 mg P/600 mg H → 600 mg each as FDC SC) every 3 weeks during cycles 5–8. After surgery, pts continued adjuvant HER2-targeted treatment only, as randomised, to complete 18 cycles. Safety was assessed by NCI-CTCAE v4.

Results

Clinical cut-off was 10 July 2020. Adverse events (AEs) are shown in the table; the most common were diarrhoea, radiation skin injury and arthralgia. Infusion-/administration-related reactions within 24 hours were higher with PH FDC SC (17%) than with P + H IV (5%), all grade 1/2 and mostly due to local injection site reactions. No grade ≥3 anaphylaxis/hypersensitivity was reported in either arm.

AEs; % of pts with ≥1: P + H IV (n = 252) PH FDC SC (n = 248)
Any 87% 89%
Grade ≥3 15% 11%
Serious 3% 4%
To monitor 46% 45%
Leading to death <1%* 0
Cardiac
Primary† 1% 2%
Secondary 4% 1%

Safety population *Related cardiac failure †Clinically significant LVEF drops: 1% of pts per arm.

Conclusions

Overall safety and tolerability, including cardiac safety, of PH FDC SC in the adjuvant phase of FeDeriCa remained comparable to P + H IV, with the exception of AEs associated with the different routes of administration. Results are in line with the expectation that most AEs with PH FDC SC or P + H IV are observed during concomitant chemotherapy.

Clinical trial identification

NCT03493854 (WO40324), 2 Feb 2018.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Funding

F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Disclosure

S-A. Im: Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Hanmi, GSK, Lilly, MSD, Novartis, Roche, Pfizer; Research grant/Funding (institution), Investigator-initiated clinical trial research grant through institution: AstraZeneca, Eisai, Daewoong Pharm, Roche, Pfizer; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A.R. Tan: Honoraria (self): Genentech, Novartis, Immunomedics, Celgene, AbbVie, Athenex, G1 Therapeutics, Eisai, Merck; Research grant/Funding (institution), Institutional clinical trial support: Roche/Genentech, Pfizer, Merck, Tesaro; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Mattar: Advisory/Consultancy, Advisory board consultant: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact sciences; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. R. Colomer: Honoraria (self): Roche, Eli Lilly, MSD, AstraZeneca; Research grant/Funding (institution): Roche, Lilly, MSD, BMS, AstraZeneca, Pfizer, Novartis; Non-remunerated activity/ies: Roche, MSD; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. D. Stroyakovskii: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. Z. Nowecki: Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. De Laurentiis: Honoraria (self), Speaker’s honoraria and advisory board honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Advisory/Consultancy: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. J-Y. Pierga: Honoraria (self): Roche, AstraZeneca, Pfizer, Amgen, Novartis, Exact Sciences, Seagen, Lilly, Pierre Fabre, MSD; Honoraria (institution): BMS, Roche, MSD, Eisai, Novartis, Sanofi; Speaker Bureau/Expert testimony: Daiichi Sankyo; Research grant/Funding (institution): Servier, Roche, Menarini Silicon Biosystems; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. K.H. Jung: Honoraria (self), Advisory board honoraria: Roche, Novartis, AstraZeneca, Takeda, Celgene; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Schem: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Aguila: Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. T. Badovinac Crnjevic: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. S. Heeson: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. Shivhare: Shareholder/Stockholder/Stock options: Roche Products Limited; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Alexandrou: Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Jackisch: Honoraria (self): AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Advisory/Consultancy: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Research grant/Funding (institution): Roche, Exact Sciences; Travel/Accommodation/Expenses: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche.

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66P - Baseline menopausal status, Ki-67 and stromal tumor-infiltrating lymphocytes (TILs) and association with outcome in triple-negative breast cancer (TNBC): exploratory analysis in GeparSixto

Abstract

Background

Several trials confirmed a survival benefit from temporary menopause during or after chemotherapy (CT) for patients with estrogen receptor-negative early BC. We investigated the impact of menopause on TNBC outcome after neoadjuvant CT (NACT).

Methods

GeparSixto evaluated the addition of carboplatin to anthracycline-taxane-based NACT. We aimed to determine the impact of menopausal status on continuous Ki-67 and TILs from baseline biopsies in all patients, and according to germline (g)BRCA1 status. TILs and gBRCA status were centrally assessed. Secondary objectives were the impact of age (≤40 vs >40 years) on baseline Ki-67 and TILs in all patients and according to gBRCA1 status, baseline menopausal status and age on pathological complete response (pCR, ypT0 ypN0), disease-free survival (DFS) and distant disease-free survival (DDFS) according to pCR.

Results

43/315 included patients had a gBRCA1 mutation (14.8%); mean Ki-67 was higher in ≤40 compared to >40 years (63.9 vs 57.9%, p=0.045) and in pre- compared to postmenopausal patients (63.1 vs 53.9%, t-test p=0.001). Mean TILs did not differ according to age (38.4 vs 33.5%, p=0.126) or menopausal status (35.9 vs 33.0%, p=0.311). There was no difference in Ki-67 or TILs according to age and menopausal status in gBRCA1 carriers. pCR rate was higher in women ≤40 years (55.4 vs 44.4%) and premenopausal (50.5 vs 36.6%). For multivariate analysis for DFS refer to the below table. Neither young age nor premenopausal status at baseline predicted for DFS. In non-pCR patients, premenopausal status at baseline but not age ≤40 years was associated with a higher relapse risk (Table). Similar results were obtained for DDFS.

pCR (ypT0 ypN0) OR (95% CI)* p-value 5-year DFS rate (N=315) HR (95% CI)* p-value 5-year DFS rate in non-pCR (N=173) HR (95% CI)* p-value 5-year DFS rate in pCR (N=142) HR (95% CI)* p-value
Age
>40 years (N=232) 41.4% 1 74.9% 1 62.7% 1 91.7% 1
≤40 years (N=83) 55.4% 1.47 (0.85-2.55) 0.167 81.2% 0.87 (0.48-1.55) 0.631 68.8% 0.83 (0.43-1.61) 0.583 91.6% 1.11 (0.26-4.68) 0.890
Menopausal status
Postmenopausal (N=123) 36.6% 1 78.4% 1 70.2% 1 92.3% 1
Premenopausal (N=192) 50.5% 1.54 (0.92-2.57) 0.101 75.3% 1.49 (0.88-2.52) 0.137 58.8% 1.79 (1.01-3.18) 0.046 91.4% 1.16 (0.26-5.20) 0.849

* adjusted for tumor stage, nodal status, tumor grade, Ki67, TILs and carboplatin use.

Conclusions

In patients with early TNBC, premenopausal compared to postmenopausal status is associated with a higher cancer cell proliferation at baseline and a higher risk of relapse in case of no pCR.

Legal entity responsible for the study

GBG.

Funding

Has not received any funding.

Disclosure

S.I. Labidi-Galy: Honoraria (self): AstraZeneca; Honoraria (institution): Novimmune. A. Schneeweiss: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Research Grant, Travel expenses, Medical writing grant: Celgene; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Expert testimony, Research Grant, Travel expenses: Roche; Honoraria (institution), Research Grant: AbbVie; Honoraria (self), Expert testimony, Honoraria: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses, Honoraria, Travel expenses: Pfizer; Honoraria (self), Honoraria: Novartis; Honoraria (self), Honoraria: MSD; Honoraria (self), Honoraria: Tesaro; Honoraria (self), Honoraria: Lilly. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Sysmex; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. J. Huober: Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AbbVie; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Celgene; Honoraria (self): Roche; Travel/Accommodation/Expenses: Daiichi; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Novartis; Honoraria (institution): Hexal. T. Link: Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Amgen; Honoraria (self): Clovis; Honoraria (self): Celgene; Honoraria (self): Lilly; Honoraria (self): Myriad. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Lilly. C. Jackisch: Honoraria (self): Celgene. P.A. Fasching: Honoraria (self): Novartis; Honoraria (institution): Biontech; Honoraria (self): Pfizer; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Merck Sharp & Dohme; Honoraria (institution): Cepheid; Honoraria (self): Lilly; Honoraria (self): Pierre Fabre; Honoraria (self): Seattle Genetics; Honoraria (self): Roche; Honoraria (self): Hexal. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): MSD. C. Denkert: Honoraria (institution), Oncobiome project: European Commission H2020; Honoraria (institution), INTEGRATE-TN project: German Cancer Aid Translational Oncology; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Molecular Health; Honoraria (institution): Myriad; Honoraria (self): Merck; Shareholder/Stockholder/Stock options, Cofounder/shareholder until 2016: Sividon diagnostics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: WO2020109570A1 - cancer immunotherapy; Licensing/Royalties: WO2015114146A1 and WO2010076322A1- therapy response. M. Untch: Honoraria (institution), All fees to the institution/employer: AbbVie; Honoraria (institution), All fees to the institution/employer: Amgen GmbH; Honoraria (institution), All fees to the institution/employer: AstraZeneca; Honoraria (institution), All fees to the institution/employer: BMS; Honoraria (institution), All fees to the institution/employer: Celgene GmbH; Honoraria (institution), All fees to the institution/employer: Daiichi Sankyo; Honoraria (institution), All fees to the institution/employer: Eisai GmbH; Honoraria (institution), All fees to the institution/employer: Lilly Deutschland; Honoraria (institution), All fees to the institution/employer: Lilly Int.; Honoraria (institution), All fees to the institution/employer: MSD Merck; Honoraria (institution), All fees to the institution/employer: Mundipharma; Honoraria (institution), All fees to the institution/employer: Myriad Genetics; Honoraria (institution): Odonate; Honoraria (institution), All fees to the institution/employer: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), All fees to the institution/employer: Roche Pharma AG; Honoraria (institution), All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Honoraria (institution), All fees to the institution/employer: TEVA Pharmaceuticals Ind Ltd.; Honoraria (institution), All fees to the institution/employer: Novartis; Honoraria (institution), All fees to the institution/employer: Pierre Fabre, Clovis Oncology, Seatlle Genetics. S. Loibl: Honoraria (institution), honorario for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), honorario for lectures and ad boards paid to institute: Celgene; Honoraria (institution), honorarium for lectures paid to institute: PriME/Medscape; Honoraria (self), lecture: Chugai; Honoraria (self), Honoraria (institution), honorario paid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), advisor honorarium paid to institute: BMS; Honoraria (institution), advisor honorarium paid to institute: Puma; Honoraria (institution), paid to institute: Immunomedics; Honoraria (institution), honorarium for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pierre Fabre; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Merck; Honoraria (institution), advisor honorarium paid to institute: EirGenix; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Amgen; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Novartis; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), grant and honorarium paid to institute: Roche; Honoraria (institution), paid to institute: Seagen; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0. All other authors have declared no conflicts of interest.

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