Neuropathie périphérique persistante induite par les taxanes chez les patientes de plus de 65 ans traitées pour un cancer du sein localisé

Médecine. Oncologie MédicaleLe traitement du cancer du sein localisé fait intervenir les taxanes qui sont neurotoxiques. La persistance de cette neuropathie périphérique induite par les taxanes (NPIT) chez les patientes âgées est peu décrite dans la littérature. Nous avons mené une étude rétrospective monocentrique sur les patientes de plus de 65 ans traitées pour un cancer du sein localisé avec un suivi de 2 ans. Nous avons évalué la fréquence de la persistance d'une NPIT de grade CTCAE 2 et 3, puis identifié les facteurs de risque pour construire un score pronostique. Parmi les 302 patientes incluses, 21% et 9% ont développé une NPIT respectivement de grade 2 et 3. Les facteurs de risque étaient l'âge (p-0,0001), l'indice de masse corporelle (p-0,0001) et le diabète (p-0,0093). Le risque était plus élevé après paclitaxel que docetaxel (p-0,0001). La NPIT est un effet secondaire fréquent et sévère des taxanes chez les patientes âgées. Des chimiothérapies sans neurotoxicité sont donc à privilégier chez elles.Early breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. We carried out a monocenter cohort study including all women over 65 years old treated with a taxane-based chemotherapy for an early breast cancer. All cases were followed-up for at least two years. We report on the frequency and risk factors and establish a prognostic score of persistent CTCAE grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9%, developed persistent TIPN of grade 2 and 3 respectively. Risk factors included age (p-0.0001), body mass index (p-0.0001), and diabetes (p=0.0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (p-0.0001). TIPN is a frequent and sometimes severe persistent side-effect of taxanes among elderly women with a major impact on quality of life. hemotherapy without neurotoxicity could be a valid option

Neuropathie périphérique persistante induite par les taxanes chez les patientes de plus de 65 ans traitées pour un cancer du sein localisé

Médecine (oncologie médicale)Le traitement du cancer du sein localisé fait intervenir les taxanes qui sont neurotoxiques. La persistance de cette neuropathie périphérique induite par les taxanes (NPIT) chez les patientes âgées est peu décrite dans la littérature. Nous avons mené une étude rétrospective monocentrique sur les patientes de plus de 65 ans traitées pour un cancer du sein localisé avec un suivi de 2 ans. Nous avons évalué la fréquence de la persistance d'une NPIT de grade CTCAE 2 et 3, puis identifié les facteurs de risque pour construire un score pronostique. Parmi les 302 patientes incluses, 21% et 9% ont développé une NPIT respectivement de grade 2 et 3. Les facteurs de risque étaient l'âge (p-0,0001), l'indice de masse corporelle (p-0,0001) et le diabète (p-0,0093). Le risque était plus élevé après paclitaxel que docetaxel (p-0,0001). La NPIT est un effet secondaire fréquent et sévère des taxanes chez les patientes âgées. Des chimiothérapies sans neurotoxicité sont donc à privilégier chez elles.Early breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. We carried out a monocenter cohort study including all women over 65 years old treated with a taxane-based chemotherapy for an early breast cancer. All cases were followed-up for at least two years. We report on the frequency and risk factors and establish a prognostic score of persistent CTCAE grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9%, developed persistent TIPN of grade 2 and 3 respectively. Risk factors included age (p-0.0001), body mass index (p-0.0001), and diabetes (p=0.0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (p-0.0001). TIPN is a frequent and sometimes severe persistent side-effect of taxanes among elderly women with a major impact on quality of life. hemotherapy without neurotoxicity could be a valid option

Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer

The therapeutic algorithm of lung cancer has recently been revolutionized by the emergence of immune checkpoint inhibitors. However, an objective and durable response rate remains low with those recent therapies and some patients even experience severe adverse events. Prognostic and predictive biomarkers are therefore needed in order to select patients who will respond. Nowadays, the only validated biomarker is the PD-L1 expression, but its predictive value remains imperfect, and it does not offer any certainty of a sustained response to treatment. With recent progresses in molecular biology, genome sequencing techniques, and the understanding of the immune microenvironment of the tumor and its host, new molecular features have been highlighted. There are evidence in favor of the positive predictive value of the tumor mutational burden, as an example. From the expression of molecular interactions within tumor cells to biomarkers circulating in peripheral blood, many markers have been identified as associated with the response to immunotherapy. In this review, we would like to summarize the latest knowledge about predictive and prognostic biomarkers of immune checkpoint inhibitors efficacy in order to go further in the field of precision immuno-oncology

Direct Targeting <i>KRAS</i> Mutation in Non-Small Cell Lung Cancer: Focus on Resistance

KRAS is the most frequently mutated oncogene in non-small cell lung cancers (NSCLC), with a frequency of around 30%, and encoding a GTPAse that cycles between active form (GTP-bound) to inactive form (GDP-bound). The KRAS mutations favor the active form with inhibition of GTPAse activity. KRAS mutations are often with poor response of EGFR targeted therapies. KRAS mutations are good predictive factor for immunotherapy. The lack of success with direct targeting of KRAS proteins, downstream inhibition of KRAS effector pathways, and other strategies contributed to a focus on developing mutation-specific KRAS inhibitors. KRAS p.G12C mutation is one of the most frequent KRAS mutation in NSCLC, especially in current and former smokers (over 40%), which occurs among approximately 12–14% of NSCLC tumors. The mutated cysteine resides next to a pocket (P2) of the switch II region, and P2 is present only in the inactive GDP-bound KRAS. Small molecules such as sotorasib are now the first targeted drugs for KRAS G12C mutation, preventing conversion of the mutant protein to GTP-bound active state. Little is known about primary or acquired resistance. Acquired resistance does occur and may be due to genetic alterations in the nucleotide exchange function or adaptative mechanisms in either downstream pathways or in newly expressed KRAS G12C mutation

Molecular Mechanism of EGFR-TKI Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Application to Biological Diagnostic and Monitoring

International audienceNon-small cell lung cancer (NSCLC) is the most common cancer in the world. Activating epidermal growth factor receptor (EGFR) gene mutations are a positive predictive factor for EGFR tyrosine kinase inhibitors (TKIs). For common EGFR mutations (Del19, L858R), the standard first-line treatment is actually third-generation TKI, osimertinib. In the case of first-line treatment by first (erlotinib, gefitinib)- or second-generation (afatinib) TKIs, osimertinib is approved in second-line treatment for patients with T790M EGFR mutation. Despite the excellent disease control results with EGFR TKIs, acquired resistance inevitably occurs and remains a biological challenge. This leads to the discovery of novel biomarkers and possible drug targets, which vary among the generation/line of EGFR TKIs. Besides EGFR second/third mutations, alternative mechanisms could be involved, such as gene amplification or gene fusion, which could be detected by different molecular techniques on different types of biological samples. Histological transformation is another mechanism of resistance with some biological predictive factors that needs tumor biopsy. The place of liquid biopsy also depends on the generation/line of EGFR TKIs and should be a good candidate for molecular monitoring. This article is based on the literature and proposes actual and future directions in clinical and translational research