Abstract 124P
Background
ER+/Her2- breast cancer (BC) is associated with lower rate of Tumor-infiltrating lymphocytic (TILs), especially CD8+ T cells. We hypothesized that attracting CD8+ T cells on the tumor site could sensitize ER+/Her2- BC to anti-PD(L)1.
Methods
Post-menopausal patients (pts) with cT2-T4 (>3cm), N0 or N+, M0 BC and Luminal A tumor defined by IHC (grade I-II, ER+ ≥ 60%, Ki67 <20%, and Her2-) have been enrolled to receive a single infusion of tremelimumab (3 mg/kg) with exemestane. After 3 weeks, pts with CD8+ T cells >10% in the tumor were enrolled in the part 2 and treated for 6 months with durvalumab 1500 mg Q4W IV and exemestane. The primary objective was the pathological response (pCR) at surgery in the CD8+ T cells enriched population.
Results
Out of the initially 96 pre-screened pts, 61 were included in part 1. Of them, 24 (39.3%) with CD8+ T cell >10% in the tumor after 3 weeks were enrolled in part 2: median age 66 years (61-71), lobular type 7 pts (29.2%), T3 or T2 tumours in 18 (75.0%) and 6 (25.0%) patients, respectively, 16 (66.7%) with N0 disease. Among the 22 pts evaluable for pCR, 1 pt (4.6%; CI 95%: 0.2% - 19.8%) achieved a pCR. The futility criterion was met and the study was stopped. An increase in CD8+T cells by 10.8% (95% CI: 6.8 – 14.7) and 4.8% (95% CI: 0.7 – 8.9) was observed between baseline and week 3 and surgery, respectively. Mean Ki67 level decreased by 6.0% (95% CI: -8.8; -3.3) and 7.0% (95% CI: -10.5; -3.4) between baseline and week 3 and surgery, respectively. TILs increased by 4.7% (95% CI: 0.7 – 8.6) and 3.8% (95% CI: -0.4 – 8.0) between baseline and week 3 and surgery, respectively. During part 1, 38 pts (22%) experienced adverse events (AEs), including 6 (15.8%) grade 3 AEs (colitis and liver enzyme elevation). In part 2, 20 pts (83.3%) developed AEs including 9 (45%) grade 3. Main grade 3 AEs included diarrhea, hypothyroidism, liver enzyme elevation and 1 pneumonitis.
Conclusions
Despite an encouraging increase in CD8+ T cells, durvalumab combined with exemestane did not demonstrate significant efficacy, as indicated by the low pCR rate. Ongoing ancillary studies may provide further insights into the immune landscape and potential refinements for future trials.
Clinical trial identification
EudraCT 2016-000764-42; NCT02997995.
Legal entity responsible for the study
Unicancer (UCBG) and Breast International Group (BIG).
Funding
The funding for the trial was provided by AstraZeneca through a research grant.
Disclosure
B. Verret: Financial Interests, Institutional, Invited Speaker: Lilly, Pfizer, Daiichi Sankyo, Novartis, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Netcancer, Pierre Fabre, Seagen, Gilead; Financial Interests, Institutional, Advisory Role: Owkins. S. Ladoire: Financial Interests, Personal, Advisory Board, advisory board: Pfizer, Novartis, AstraZeneca, Sanofi, Daiichi, Gilead, Menarini-Stemline; Financial Interests, Personal, Expert Testimony, advisory board, expert testimony: Astellas; Financial Interests, Personal, Expert Testimony, expert testimony, invited speaker: Janssen, Ipsen; Financial Interests, Personal, Invited Speaker, invited speaker: BMS, Seagen, Exact Science; Financial Interests, Personal, Invited Speaker, invited speaker, expert testimony: Lilly; Financial Interests, Institutional, Research Grant, research grant: Novartis, Eisai, BMS. F. Dalenc: Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Gilead, Novartis. E.G.C. Brain: Financial Interests, Personal, Invited Speaker, Webinars, optimized endocrine therapy for older breast cancer patients: Eli Lilly; Financial Interests, Personal, Advisory Board, Palbociclib and older breast cancer patients: Pfizer; Financial Interests, Personal, Invited Speaker, Symposium HER2+ MAO conference 03/21: Seagen; Financial Interests, Personal, Invited Speaker, ELEVATE 10/2021 and ABC 11/2021 meetings: Pfizer; Financial Interests, Personal, Other, IDMC DESTINY 05: DAIICHI; Financial Interests, Personal, Advisory Board, GCSF and FN in older patients: SANDOZ; Financial Interests, Personal, Advisory Board, Underserved Patients Populations with breast cancer, advisory board: Pfizer; Financial Interests, Personal, Invited Speaker, Management of older patients with cancer, series of seminars in Canada for HCP: Pfizer; Financial Interests, Personal, Invited Speaker, Symposium during SIOG annual meeting 1/11/2023: Daiichi; Financial Interests, Personal, Invited Speaker, RWD in myeloma and older patients, Prohgress, 17/11/2023: Takeda; Financial Interests, Personal, Invited Speaker, TIBCS, taipei, older patienst with breast cancer, 21/09/2023: Pfizer; Financial Interests, Personal, Invited Speaker, Series of lectures in Montreal/Quebec on breast cancer management in older ones, 09-13/10/2023: Pfizer; Financial Interests, Personal, Advisory Board, Elacestrant and BC, 13/03/2023: Menarini; Financial Interests, Personal, Invited Speaker, 29/03/2023 symposium during SFH annual meeting, RWD and older patients: Incyte; Financial Interests, Institutional, Invited Speaker, APPALACHES study EORTC 1745: Pfizer; Financial Interests, Institutional, Invited Speaker, TOUCH study (IBCSG 55/GERICO study): Pfizer; Financial Interests, Institutional, Invited Speaker, DEESTINY 09: DAIICHI; Financial Interests, Institutional, Invited Speaker, DESTINY 06: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, SERENA 06: AstraZeneca. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. H. Vegas: Financial Interests, Funding: Eisai, Novartis, AstraZeneca, Pfizer. A. Mailliez: Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, Novartis, Roche; Financial Interests, Personal, Invited Speaker: Pierre Fabre, OSEUS, Seagen, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Expert Testimony: GSK. S. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. A. Prat: Financial Interests, Personal, Invited Speaker: Roche, 1TRIALSP, S.L.; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L.,; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. F. André: Financial Interests, Personal, Advisory Board: Lilly France; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, OWKIN, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi, Guardant Health, Owkin. All other authors have declared no conflicts of interest.