249P - Neoadjuvant chemotherapy in inflammatory breast cancer: A meta-analysis of 10 trials of the German Breast Group (GBG)

Background

Inflammatory breast cancer (IBC) is a rare clinic-pathologic entity associated with poor clinical outcome. Currently, no approved IBC-specific systemic treatment recommendations are available. We investigated clinical, pathological, and prognostic features associated with IBC in a meta-analysis of 10 neoadjuvant trials conducted by GBG.

Methods

We performed a post-hoc analysis of patients (pts) from the G3-G8, GX, GAIN-2, TECHNO, and PREPARE trials, aiming to compare early breast cancer (eBC, cT1-3) with locally advanced breast cancer (LABC, cT4a-c) and IBC (cT4d) concerning clinic-pathological features and prognostic behavior after adjusting for selected clinical factors.

Results

Out of 10.115 pts included 9.101 pts (90.0%) had eBC, 487 (4.8%) LABC and 527 (5.2%) IBC. Pts with LABC and IBC were older and had a higher body mass index compared to eBC pts. IBC pts presented more often with nodal involvement, hormone receptor negative or human epidermal growth factor receptor 2 positive (HER2+) disease. Pathological complete response (pCR) rates (ypT0/is ypN0) were significantly lower in LABC and IBC pts compared to eBC pts (eBC 33.6% vs LABC 17.2%, p<0.001 vs IBC 24.5%, p=0.010). Multivariate cox frailty models revealed LABC and IBC compared to eBC as independent risk factors for recurrence and death (disease-free survival; LABC hazard ratio [HR] 1.59, 95% CI 1.23-2.06; IBC HR 2.45, 95% CI 1.99-3.02; overall survival [OS]: LABC HR 1.97, 95% CI 1.43-2.70; IBC HR 3.05, 95% CI 2.37-3.93, all p<0.001) by considering established prognostic factors like nodal involvement, BC subtype or grading. Triple negative (TN) IBC pts had strikingly poor prognosis (median OS 31.3 months; 2-years OS 55.4%) compared to pts with TN eBC or LABC, respectively, (2-years OS; eBC 91.0%, LABC 74.8%) or HER2+ and luminal IBC (2-years OS; HER2+ 92.1%, luminal 87.2%). Survival differences were consistently observed in all trials and sustained with longer FU. No treatment showed specific benefit for pts with IBC.

Conclusions

Pts with IBC, especially TN IBC should be offered trial participation and upfront access to more efficient therapies given the limited prognosis with standard treatments.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The funding for the 10 neoadjuvant GBG trials included in this study was provided by the following sponsors: G3 (Amgen, Roche, Sanofi-Aventis), G4 (Roche Germany), G5 (Celgene Germany, Roche Germany), G6 (GSK), G7 (Roche, Celgene), G8 (Teva, Amgen, Vifor, Roche), GX (Amgen, Celgene), GAIN-2 (Roche, Amgen, Celgene), TECHNO (Roche), and PREPARE (Amgen, Bristol-Myers Squibb Germany).

Disclosure

P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, Astrazeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis, Medac, Menarini, Veracyte; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead, Mylan; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Local PI: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. P. Wimberger: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly GmbH, Roche GmbH, MSD, Eisai, GSK, Gilead, Pfizer, Novartis. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Roche, Lilly, Diaceutics, VmScope digital pathology software; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche, Myriad, German Breast Group. J. Huober: Financial Interests, Other, Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Seagen, Gilead, Diachii; Financial Interests, Advisory Board, Consulting: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Gilead, Diachii; Financial Interests, Other, Travel expenses: Roche, Novartis, Diachii, Gilead. T. Link: Financial Interests, Officer, Honoraria: Amgen; Financial Interests, Other, Honoraria: Roche, MSD, Novartis, Pfizer, Lilly, GSK, Gilead, AstraZeneca, Daiichi Sankyo, Stemline, Seagen; Financial Interests, Advisory Board: MSD, Roche, Pfizer, Lilly, Myriad, Eisai, GSK, Gilead, Daiichi Sankyo, Roche, AstraZeneca; Financial Interests, Other, Support for attending meetings and/or travel: Pfizer, AstraZeneca, Gilead, Daiichi Sankyo, Stemline. J. Rey: Financial Interests, Institutional, Funding: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Seagen, AbbVie, AstraZeneca, BMS, Daiichi Sankyo, Gilead, Molecular Health, Novartis, Roche, Pfizer. J. Holtschmidt: Financial Interests, Institutional, Funding, Paid to the institution: Abbvie, AstraZeneca, BMS, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Personal fees outside the submitted work: MSD Oncology, Novartis, Palleos Healthcare, Pfizer, Roche Pharma, Seagen; Non-Financial Interests, Institutional, Other, Medical writing: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche Pharma, Seagen, Hologic. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, Abbvie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen, Stemline-Menarini; Financial Interests, Institutional, Advisory Board: Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Advisory Board, Ki67 Quantifier: VMscope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health, Greenwich Life Sciences; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. All other authors have declared no conflicts of interest.