262P - Predictive clinico-biological factors of toxicity associated to neo-adjuvant chemo- immunotherapy in early-stage triple-negative breast cancer

Background

Pembrolizumab is now combined with neoadjuvant chemotherapy (CT) for ≥T2 and/or N≥1 early triple-negative breast cancer. The clinically meaningful 13.6% pCR benefit and 7.7 % EFS benefit at 36 months is at cost of a significant toxicity, potentially irreversible in a curable population. Identification of predictive factor of toxicity is an unmet medical need.

Methods

We included all triple negative early breast cancer patients treated with the Keynote 522 neoadjuvant regimen between April 2022 and July 2023 at Institut de Cancérologie de l’Ouest France. Patients received at least one cycle of treatment. CT related adverse events (≥ grade III crAE) and any grade immune therapy related AE (irAE) according to CTCAE v 5.0 were collected.

Results

106 patients (96.2% of ≥cT2 and/or 53.7% ≥cN1 tumors) were included and pCR rate was 63%. Median age was 52.4 years [28.2-85.6] with 13 (12.2%) patients >70 years. Significant medical history included current or former smoking (40.6%), BMI>25 (48.1%), cardiovascular disease (23.6%) and autoimmune disease (3%). Overall, 56.6 % of pts required a dose reduction, 16% (n=17) and 8.4 % (n=9) discontinued any treatment or pembrolizumab respectively. TrAE led to hospitalization in 12 patients including irAE (n=10) and crAE (n=2). crAE included febrile neutropenia in 15% (n=16) of patients. irAE of all grades was 54.7% (n=58), including thyroid dysfunction (n=26, 24.5%), hypophysitis (n=3), and optic neuritis (n=1). One case of crAE leading to death was reported (sepsis). pCR rate was 64.8% and 64.4% in patients with or without irAE respectively. In univariate analysis, young age as a continuous variable was a significant associated with irAE (0.034) while BMI, leucocyte count at baseline, neutrophil-to-lymphocyte ratio (NLR) were not. Current or former smoking was significantly associated with crAE.

Conclusions

In this real-life cohort of early stage TNBC patients treated with neoadjuvant chemotherapy and pembrolizumab, a high rate of irAE and discontinuation due to toxicity were witnessed. Young age was statistically associated with probability of irAE. Further studies are needed to confirm these findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institut de Cancérologie de l'Ouest, FRANCE.

Funding

Has not received any funding.

Disclosure

J. Frenel: Financial Interests, Personal, Advisory Board: pfizer, novocure, pierre fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, amgen, Eisai; Financial Interests, Institutional, Advisory Board: Exactscience, lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Coordinating PI: AstraZeneca, Seagen; Financial Interests, Local PI: MSD, Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD. A. Patsouris: Financial Interests, Institutional, Advisory Board: Lilly, Gilead, AstraZeneca, Novartis, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Other, teaching: Gilead; Financial Interests, Institutional, Invited Speaker: Novartis. P. Augereau: Financial Interests, Institutional, Advisory Board: Azd Daichy, MSD; Financial Interests, Institutional, Invited Speaker: GSK, Novartis, Seagen. M. Campone: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Sanofi, Daiichi Sankyo, Lilly, Stemline, Gilead, Seagen; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly. M. Robert: Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Other, travel and congress fees: AstraZeneca; Non-Financial Interests, Personal, Training: Novartis. All other authors have declared no conflicts of interest.