Centre François Baclesse

MOVIE assessed the enhancement of immunotherapy activity in advanced breast cancer (BC) tumors with metronomic chemotherapy associated to dual ICI combination.

MOVIE was a national, multicenter, open-label, phase I/II, non-randomized. It tested the antitumor activity and safety of metronomic vinorelbine associated with anti-PD-L1 durvalumab + anti-CTLA-4 tremelimumab using a Bayesian approach. Here, we report on the cohort of patients with advanced BC during MOVIE phase 2. Patients were aged≥18 years with histologically confirmed locally advanced or metastatic breast tumors, resistant to conventional therapies, presenting a measurable disease according to RECISTv1.1. They received vinorelbine 40 mg thrice a week, and durvalumab 1500 mg plus tremelimumab 75 mg at day 1 of 28-day cycles. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Between 2018 and 2020, 30 BC patients, including 19 triple negative breast cancers were enrolled. Mean estimated CBR (95 % credible interval) using a non-informative prior was 15.6 % (5.5-29.8). ORR was 6.7 % (2 PR), median PFS 1.8 months (95 % confidence interval [CI]:1.8-1.8) and median OS 8.8 months (95 %CI:5.6-12.8). Fifteen patients (50.0 %) presented grade≥3 ICI-related adverse events (AEs), mostly fatigue (N = 3; 10.0 %). Grade≥3 vinorelbine-related AEs mostly included neutropenia (N = 5; 16.7 %), and fatigue (N = 3; 10.0 %). Four (13.3 %) patients discontinued their treatment due to treatment-related toxicity. There was no treatment-related death.

Metronomic vinorelbine and durvalumab plus tremelimumab showed limited antitumor activity in pretreated advanced BC. Alternative strategies are warranted to enhance the efficacy of ICI in those tumors.

This trial is registered with ClinicalTrials.gov, identifier NCT03518606.

Breast cancer (BC) survivors receiving adjuvant treatments often report clinically relevant cancer-related cognitive complaints (CRCC), which have a significant impact on quality of life. We aimed to develop a comprehensive model of prediction of CRCC, including clinical and serum inflammatory protein data.

We included 9575 stage I-III BC patients from the CANTO cohort (NCT01993498). Data were collected at diagnosis, 2(year-2) and 4(year-4) years post-diagnosis. Outcome of interest was CRCC (cognitive dimension of the EORTC QLQ-C30 questionnaire, score < 75/100) at year-2 and year-4. Serum inflammatory markers (IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IFNg, IL-1, IL1Ra, TNF-a, CRP) were available in a subset of patients with hormone-receptor-positive BC. Multivariable logistic regression models assessed associations of baseline clinical and inflammatory variables with CRCC.

Rates of CRCC were 31% (diagnosis), 39% (year-2), and 37% (year-4). Baseline validated predictors of CRCC reported at year-2 were chemotherapy, pre-treatment CRCC, pain, and fatigue; predictors of CRCC reported at year-4 were pre-treatment CRCC, pain, and anxiety. Other clinically relevant factors associated with CRCC at both timepoints during model development were pre-treatment insomnia, receipt of endocrine therapy, and younger age/premenopausal status. No significant associations were observed between inflammatory markers and CRCC.

Approximately one-in-three BC survivors in this cohort reported CRCC at diagnosis, with this rate being stable until year-4 after diagnosis. Pre-treatment symptom burden and chemotherapy were validated as risk factors for long term CRCC. No associations between inflammatory markers and self-reported CRCC emerged from this study.