Abstract 138P
Background
PH IV/PH FDC SC is standard of care for HER2-positive BC and usually given with chemotherapy, all of which can trigger anaphylaxis/hypersensitivity. In the US, PH FDC SC can be administered by healthcare professionals in patients’ (pts’) homes. There is a need to further characterise risk of anaphylaxis/hypersensitivity with PH IV/PH FDC SC to support safe administration outside of clinics. We assessed occurrence, incidence and severity of these events in key Roche clinical trials of PH IV/PH FDC SC, and did a time–trend analysis (by cycle) for metastatic BC (MBC) and early BC (EBC) studies.
Methods
A cumulative search for anaphylaxis/hypersensitivity (Roche Standard Adverse Event Group Terms) across all pivotal trials cited in the current EMA P IV/PH FDC SC SmPCs. MBC: CLEOPATRA (NCT00567190; PMID 22149875, 23602601, 25693012; 32171426), MetaPHER (NCT02402712; 33748921); EBC: APHINITY (NCT01358877; 28581356, 33539215), NeoSphere (NCT00545688; 22153890, 27179402), TRYPHAENA (NCT00976989; 23704196, 29223479), BERENICE (NCT02132949; 29253081, SABCS 2017 P5-20-04), FeDeriCa (NCT03493854; 33357420), PHranceSCa (NCT03674112; ESMO 2020 165MO).
Results
This analysis includes 4772 pts. Incidence and intensity of anaphylaxis/hypersensitivity events: Table: 138P
| % of pts | PH IV MBC | PH IV EBC | PH FDC SC |
| All-grade | 3–11% | 1–13% | 2–3% |
| Grade ≥3 | ≤2% | 0–3% | <1% |
Discontinuations due to anaphylaxis/hypersensitivity were rare for PH IV (generally <1% except two TRYPHAENA arms: 1% and 3%); no discontinuations of PH FDC SC have been recorded so far. Time–trend analyses showed that most events were reported during the first 6–8 cycles with concurrent chemotherapy, with a decrease in later cycles (except MetaPHER).
Conclusions
PH IV/PH FDC SC for HER2-positive BC were well tolerated, with few grade ≥3 anaphylaxis/hypersensitivity events reported with PH IV and no grade ≥3 related events with PH FDC SC. Most events occurred during chemotherapy.
Clinical trial identification
NCT00567190, NCT02402712, NCT01358877, NCT00545688, NCT00976989, NCT02132949, NCT03493854, NCT03674112.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Alison McGonagle, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
S.M. Swain: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd./Genentech, Inc.; Financial Interests, Personal, Advisory Role: Exact Sciences (Genomic Health); Financial Interests, Personal, Advisory Role: Molecular Templates; Financial Interests, Personal, Advisory Role: Silverback Therapeutics; Financial Interests, Personal, Advisory Role: Tocagen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Natera; Financial Interests, Personal, Advisory Role: Beijing Medical Foundation; Financial Interests, Personal, Advisory Board: Inivata; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd./Genentech, Inc.; Financial Interests, Personal, Research Grant: KailosGenetics; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: BMS; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Lilly; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: F. Hoffmann-La Roche Ltd./Genentech, Inc.; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Daiichi-Sankyo; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Caris Life Sciences; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. A. Tan: Non-Financial Interests, Institutional, Research Grant: Genentech/Roche; Non-Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Research Grant: Merck; Non-Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. L. Gianni: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: ADC Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech, Inc.; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Oncolytics Biotech; Financial Interests, Personal, Advisory Board: Odonate Therapeutics; Financial Interests, Personal, Advisory Board: Onkaido Therapeutics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Synthon and Zymeworks; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Revolution Medicines; Financial Interests, Personal, Advisory Role: Forty Seven; Financial Interests, Personal, Advisory Role: Metis Precision Medicine; Financial Interests, Personal, Advisory Role: Menarini Ricerche; Financial Interests, Personal, Advisory Role: Synaffix; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Revolution Medicines; Non-Financial Interests, Personal, Other, Patent; EPA 12195182.6 12196177.5-Roche, pending (coinventor): Roche; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. S. Kümmel: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Genomic Health; Financial Interests, Personal, Advisory Role: Exact Science; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Daiichi Sanyko; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Somatex; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: PFM medical; Financial Interests, Personal, Advisory Role: Lily; Non-Financial Interests, Personal, Other: Roche; Non-Financial Interests, Personal, Other: Daiichi Sankyo; Non-Financial Interests, Personal, Other: Lily; Non-Financial Interests, Personal, Other: Sonoscape; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. C. Dang: Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Honoraria: Genentech, Inc.; Financial Interests, Personal, Other, Honoraria: Daiichi-Sankyo; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Puma Biotechnology; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. A. Schneeweiss: Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Celgene; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: Lily; Financial Interests, Personal, Other, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: Seagen; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. J. O'Shaughnessy: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Agendia; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Genentech, Inc.; Financial Interests, Personal, Advisory Role: Immunomedics; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Odonate; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Puma; Financial Interests, Personal, Advisory Role: Prime Oncology; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. H. Liu: Financial Interests, Personal, Full or part-time Employment: Genentech; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. C. Aguila: Financial Interests, Personal, Full or part-time Employment, Clinical Scientist/Medical Director: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. S. Heeson: Financial Interests, Personal, Full or part-time Employment: Roche Products Ltd.; Financial Interests, Personal, Stocks/Shares: Roche Products Ltd.; Non-Financial Interests, Personal, Other, Patent; PH FDC SC: Roche; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. H. Macharia: Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: F. Hoffman-La Roche. E. Restuccia: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: Genentech, Inc; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. S. Loibl: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: AbbVie; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Celgene; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Advisory Board: PriME/ Medscape; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Research Grant: Teva; Financial Interests, Personal, Research Grant: Vifor; Financial Interests, Institutional, Research Grant: Daiichi-Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Samsung; Financial Interests, Institutional, Advisory Board: Eirgenix; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Puma; Financial Interests, Personal, Research Grant: Immunomedics; Non-Financial Interests, Personal, Other, Patent EP14153692 .0 pending: Roche; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Advisory Board: MSD.