A case of a life-threatening toxicity following capecitabine treatment: advocacy for dihydropyrimidine dehydrogenase deficiency screening

We discuss a life-threatening case of capecitabine toxicity due to the presence of a heterozygous variant on exon 14 (c.1905+1G>A, rs3918290) of the dihydropyrimidine dehydrogenase gene (DPYD). We advocate the need for dihydropyrimidine dehydrogenase deficit screening, which could become mandatory in Belgium, as in France, before any fluoropyrimidine administration to avoid cases of foreseeable toxicity

Tumour-agnostic plasma assay for circulating tumour DNA predicts outcome in recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with a PD-1 inhibitor.

Only 15-20% of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients derive long-term benefit from nivolumab or pembrolizumab. We developed a circulating tumour DNA (ctDNA) tumour-agnostic assay aimed at the early prediction of single agent programmed cell death 1 (PD1) inhibitor efficacy in R/M SCCHN. Our tumour-agnostic assay included 37 genes frequently mutated in R/M SCCHN and two HPV16 genes. Primary endpoint was the concordance between ctDNA kinetics (ΔctDNA) and the best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1. ΔctDNA was defined as the difference in mean variant allele frequency (VAF) between the on-treatment sample harvested 6-10 weeks (FU1) after PD1 inhibitor initiation and the pre-treatment plasma sample (ΔctDNA = mean FU1 VAF - mean pre-treatment VAF). ctDNA was detected in 35/44 (80%) of the pre-treatment plasma samples. The concordance between ΔctDNA and imaging response was observed in 74%. Median progression-free survival was 8.6 months in the favourable ΔctDNA group and 2.5 months in the unfavourable ΔctDNA group (p = 0.057). Median overall survival (OS) was 18.1 and 8.2 months in the favourable and unfavourable ΔctDNA groups, respectively (p = 0.13). In patients with PD-L1 expressing SCCHN (Combined Positive Score ≥1), OS was significantly better in patients with favourable ΔctDNA compared with patients with unfavourable ΔctDNA: median OS was 41.5 and 8.4 months (p = 0.033), respectively. Tumour-agnostic ctDNA analysis for human papillomavirus (HPV)-negative and HPV-positive R/M SCCHN is feasible. ctDNA kinetics show promising results in predicting the efficacy of PD1 inhibitors in R/M SCCHN

Theia: Faint objects in motion or the new astrometry frontier

In the context of the ESA M5 (medium mission) call we proposed a new satellite mission, Theia, based on relative astrometry and extreme precision to study the motion of very faint objects in the Universe. Theia is primarily designed to study the local dark matter properties, the existence of Earth-like exoplanets in our nearest star systems and the physics of compact objects. Furthermore, about 15 % of the mission time was dedicated to an open observatory for the wider community to propose complementary science cases. With its unique metrology system and "point and stare" strategy, Theia's precision would have reached the sub micro-arcsecond level. This is about 1000 times better than ESA/Gaia's accuracy for the brightest objects and represents a factor 10-30 improvement for the faintest stars (depending on the exact observational program). In the version submitted to ESA, we proposed an optical (350-1000nm) on-axis TMA telescope. Due to ESA Technology readiness level, the camera's focal plane would have been made of CCD detectors but we anticipated an upgrade with CMOS detectors. Photometric measurements would have been performed during slew time and stabilisation phases needed for reaching the required astrometric precision

Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial.

Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.info:eu-repo/semantics/publishe