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.

Oligometastatic head and neck squamous cell carcinoma is a distinct clinical state inadequately addressed in current metastatic disease trials. This narrative review is based on historical literature and recently published data of the Omet trial. The Gortec 2014-04 Omet phase II randomized trial investigated whether genuine metachronous oligometastases in head and neck squamous cell carcinoma, characterized by a limited number (up to three) of lesions not induced by prior systemic therapy, may benefit from a "de-escalation strategy" using curative-intent stereotactic ablative radiotherapy alone rather than strategies relying on systemic treatments upfront. Randomized phase II-III trials are scarce on head and neck squamous cell carcinoma. In the Omet trial, survival at 1 year exceeded 85 % in both arms. Progression-free survival was, as anticipated, slightly longer in the group chemotherapy and stereotactic ablative radiotherapy (10 months versus 7.5 months) but without deleterious impact upon metastatic relapse. Stereotactic ablative radiotherapy alone showed significantly lower grade 3-4 toxicity (8.8 % versus 60 %). Quality of life declined less with stereotactic ablative radiotherapy alone. Poor prognostic factors included male sex and multiple metastases. Major protocol deviations correlated with worse outcomes. Stereotactic ablative radiotherapy offers a viable, less toxic alternative to systemic therapy for genuine oligometastatic head and neck squamous cell carcinoma, warranting refined patient selection and further research. Despite its role as a new standard-of-care, the role of immunotherapy remains uncertain in the oligometastatic setting and requires specific studies in oligometastatic head and neck squamous cell carcinoma to challenge this new option.

Several cases of radio-induced neurotrophic keratitis had been observed after proton therapy delivering a mean corneal dose of ≥50 GyRBE. We conducted a prospective exploratory study to assess corneal sensitivity in subsequent patients undergoing proton therapy for cephalic extraocular tumors.

Forty-three patients (85 eyes) treated with high-energy proton therapy were included in this prospective, single-center, observational cohort study. All patients had their corneal sensitivity measured using Cochet–Bonnet esthesiometer, before and average 6 months after irradiation. Ocular surface was clinically assessed for stromal opacity, corneal thinning, corneal perforation, superficial punctate keratitis graded according to Oxford classification, and tear break-up time. Cornea and extraocular sensitive innervation structures of cornea were contoured and their dose metrics assessed.

No severe corneal damage was detected. Corneal sensitivity, superficial punctate keratitis according to Oxford classification, and tear break-up time did not vary significantly after irradiation. The mean value of maximal dose to cornea and extraocular sensory innervation of cornea were 10.7 GyRBE and 42.0 GyRBE, respectively. Doses to cornea and its innervation structures were not associated with significant changes in corneal sensitivity (P = 0.423 and P = 0.614). A dose per fraction greater than 2 GyRBE was significantly associated (P = 0.033) with a decrease of corneal sensitivity after proton therapy.

This pilot study showed no excess risk of damage to corneal sensitivity 6 months after proton therapy, as doses to the cornea could be minimized. However, based on prior neurotrophic keratitis cases for corneal doses above 50 GyRBE, further investigation is needed to establish the impact of high-dose proton therapy on corneal sensitivity.