Tremelimumab plus durvalumab combined to metronomic oral vinorelbine: Results from the breast cancer cohort of the phase II MOVIE study
Purpose: MOVIE assessed the enhancement of immunotherapy activity in advanced breast cancer (BC) tumors with metronomic chemotherapy associated to dual ICI combination. Methods: MOVIE was a national, multicenter, open-label, phase I/II, non-randomized. It tested the antitumor activity and safety of...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-10-01
|
| Series: | Breast |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977625005661 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Purpose: MOVIE assessed the enhancement of immunotherapy activity in advanced breast cancer (BC) tumors with metronomic chemotherapy associated to dual ICI combination. Methods: 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). Results: 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. Conclusion: 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. Trial registration: This trial is registered with ClinicalTrials.gov, identifier NCT03518606. |
|---|---|
| ISSN: | 1532-3080 |