Abstract 79P
Background
Dose-dense sequential (dds) chemotherapy has tremendously changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a now widely used chemotherapeutic regimen consisting of 4 cycles of cyclophosphamide and epirubicin q2 weeks, followed by 4 cycles of docetaxel q3 weeks. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort.
Methods
Totally, 1,054 patients were prospectively enrolled in the current study with 1,024 patients being eligible, while adequate tissue was available for 659 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry.
Results
Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. The median DFS and overall survival (OS) had not been reached yet at the time of data cut-off for the analysis, while the 10-year DFS and OS rates were 78.4% (95% CI 75.0-81.5) and 81.7% (95% CI 79.0-84.1), respectively. The studied regimen was well tolerated with 94.7% of the patients completing the full course of adjuvant chemotherapy (8 cycles), while the rest of them discontinued the treatment, mainly due to non-fatal reasons. Only a very small percentage of patients faced clinically significant myelotoxicity. Interestingly, higher CD8+ T cells in the tumor microenvironment were associated with an improved long-term survival outcome.
Conclusions
In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of infiltrating CD8+ lymphocytes in BC patients with early stage disease.
Clinical trial identification
ACTRN12616001043426.
Legal entity responsible for the study
Hellenic Cooperative Oncology Group (HeCOG).
Funding
Hellenic Society of Medical Oncology (HeSMO), Hellenic Cooperative Ongology Group (HE10/10).
Disclosure
F.D. Dimitrakopoulos: Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel: Roche, MSD. D.G. Pectasides: Financial Interests, Personal, Advisory Role: Roche, MSD, Astellas; Financial Interests, Personal, Other, Honoraria: Roche, MSD, Astellas. A. Koutras: Financial Interests, Personal, Advisory Board: Pierre Fabre, AstraZeneca, Gilead, Pfizer, Genesis, MSD, BMS; Financial Interests, Personal, Invited Speaker: Sanofi, Gilead; Financial Interests, Personal, Other, TRAVEL, ACCOMMODATIONS: Rafarm, Lilly, Ipsen, Gilead, Pfizer; Financial Interests, Institutional, Funding: Lilly, Pfizer, Merck; Financial Interests, Institutional, Research Grant: AstraZeneca, Pierre Fabre, BMS, DEMO, FARAN, Amgen, Roche, Ipsen, GALENICA, WIN MEDICA. F. Zagouri: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi, Eli Lilly, Merck, MSD, Genesis-Pharma, Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daiichi, Eli Lilly, Merck, MSD, Genesis-Pharma, Roche. H. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, PIERRE FABRE; Financial Interests, Personal, Invited Speaker: MSD, BMS, NOVARTIS, PIERRE FABRE, SANOFI; Financial Interests, Invited Speaker: AMGEN, REPLIMMUNE; Financial Interests, Institutional, Invited Speaker: AMGEN, MSD, BMS, REPLIMMUNE, IOVANCE; Financial Interests, Institutional, Research Grant: BMS, PFIZER. G. Fountzilas: Financial Interests, Personal, Advisory Board: Pfizer, Novartis; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Novartis; Financial Interests, Personal, Stocks/Shares: Genprex, Daiichi Sankyo , RFL Holdings, FORMYCON. All other authors have declared no conflicts of interest.