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 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.