High risk of recurrence for grade II meningioma: a 10-year multicenter analysis of prognosis factors Laura Bender, François Somme, Benoît Lhermitte, Guido Ahle, Mathieu Boone, Marie Blonski, Celso Pouget, Gilles Truc, Hélène Cebula, Georges Noël

Antibody-drug conjugates (ADCs) are an emerging class of therapeutics for lung cancer, and several are currently in development for this malignancy. The structure of these molecules is based on an antibody that targets a protein on the lung cancer cell surface and a cytotoxic payload attached by a linker. Many protein targets, including TROP2, c-MET, CEACAM5, HER2, and HER3 have been identified. In metastatic non-small cell lung carcinoma (NSCLC) without alterations in oncogenic drivers, platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) targeting the programmed death-1/programmed death-ligand 1 (PD1/PDL1) interaction are the standard first-line treatments. In patients with EGFR-mutated or ALK-rearranged NSCLC, tyrosine kinase inhibitors (TKIs) are recommended. However, although the prognosis of patients with metastatic NSCLC differs between such with and without alterations in oncogenic drivers, most patients eventually experience disease progression. A novel therapeutic class is needed in routine practice to overcome the mechanisms of resistance to ICIs and EGFR/ALK TKIs. Several ADCs have already been approved for other cancers, such as breast cancer and urothelial carcinoma. This review summarizes the knowledge about the efficacy and tolerance profiles of ADCs targeting TROP2, HER2, HER3, CEACAM5 and c-MET in metastatic NSCLC with and without alterations in oncogenic drivers.

Meningioma is the most common adult primary intracranial tumor. Malignant meningioma is a rare variant of meningioma. The prognosis for the patients with these tumors is poor, due to the tumor’s capacity for relapse and to develop distant metastases. These tumors can present the same evolutionary course as aggressive carcinoma. We report the case of distant brain and gastro-intestinal tract (GIT) metastases. A 78-year-old patient developed malignant meningioma with a Ki-67 proliferative index of 40%. According to guidelines, surgery followed by postoperative radiotherapy (RT) was performed. Three months after the end of RT, he presented histologically proven meningioma distant brain and GIT metastases. To our knowledge, this is the first case of meningioma GIT metastases. Also, we report the difficulty to confirm the diagnosis of meningioma metastases. Indeed, malignant meningioma has the same histopathological features as melanoma or carcinoma. The standard of care for the management of malignant meningioma is gross total surgery followed by postoperative radiotherapy. Metastatic meningioma is uncommon and no guidelines for the management of recurrent or metastatic meningioma have yet been published. However, several studies reported systemic therapeutic options such as antibody against VEGF, somatostatin analogs, PDGF-R, and VEGF-R tyrosine kinase inhibitors, in the case of recurrent or metastatic meningioma. We also made a review of the actual literature of systemic treatment options for metastatic meningioma.

ROS1 gene rearrangements define a distinct molecular subtype of non-small cell lung cancer (NSCLC), occurring in approximately 2% of cases and frequently associated with younger age, non-smoker status, and a high incidence of brain metastases. The discovery of ROS1 as an oncogenic driver has led to the development of targeted tyrosine kinase inhibitors (TKIs). Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape.

The combination of endocrine treatment with cycline-dependent-kinase 4/6 inhibitor is the new standard of treatment in hormone receptor-positive HER2 negative metastatic breast cancer. The optimal subsequent treatment after CDK4/6 inhibitor remain unclear. As recommended by standard guidelines, capecitabine, an oral chemotherapy is a therapeutic option in endocrine resistant metastatic breast cancer. The objective of this study was to evaluate capecitabine efficacy after disease progression under combination of ET and CDK4/6 inhibitor in a hormone receptor positive metastatic breast cancer population. Patients progressing under CDK 4/6 inhibitor plus ET and treated with capecitabine, between January 2016 and December 2020, were retrospectively included. Primary endpoint was time to treatment failure (TTF) on capecitabine. Logistic regression were used to identify predictive factors: exclusive bone versus visceral metastases, first-line versus ≥ 2 lines of combination therapy, aromatase inhibitor (AI) versus fulvestrant. Fifty-six patients with a 62-year median age (IC95% 42-81) were analyzed. The CDK 4/6 inhibitor and ET combination was prescribed in first-line setting in 26 patients (46%). Twenty-five patients (44%) had exclusive bone metastasis. Median TTF was 6.1 months. Six patients discontinued capecitabine due to toxicity. Outcomes were not significantly different regardless of metastases localization, ET, and treatment line of the combination of CDK 4/6 inhibitor and ET. Median PFS was 7.1 months. Median OS was 41.3 months. Compared to other data of capecitabine prescribed in patients with hormonal resistant MBC, this retrospective study suggests that capecitabine remains effective after CDK 4/6 inhibitor plus ET progression, regardless of therapeutic-line setting and metastases localization. Cycline dependant kinase 4/6 inhibitor plus endocrine therapy have become the standard of care in metastatic hormone receptor positive (HR+) breast cancer (BC). Few data reported the optimal subsequent therapy after progression under the combination. Capecitabine is a therapeutic option in endocrine resistant HR+/HER2- metastatic breast cancer. Data evaluating efficacy of capecitabine after disease progression on endocrine therapy plus cycline-dependant kinase 4/6 inhibitor are poor. This study showed a 6.1-month median time to treatment failure on capecitabine. Capecitabine remained effective regardless of therapeutic-line setting and metastases localization.