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Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFAnonymized data from BRAFForty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAF

BACKGROUND/AIM Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. PATIENTS AND METHODS Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics. RESULTS Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. CONCLUSION Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients.

Introduction: LAG-3 is an inhibitory immune checkpoint molecule that suppresses T cell activation and inflammatory cytokine secretion. T cell density in the tumor microenvironment of colon cancer plays an important role in the host’s immunosurveillance. We therefore hypothesized that LAG-3 expression on tumor-infiltrating lymphocytes (TILs) predicts outcome in patients with stage II colon cancer. Patients and Methods: Immunohistochemical staining for LAG-3 was performed on tissue microarrays (TMAs) of formalin-fixed paraffin-embedded tissue from 142 stage II colon cancer patients. LAG-3 expression was assessed in TILs within both the tumor front and tumor center and scored as either positive or negative. The primary endpoint was disease-free survival (DFS). Results: In patients diagnosed with stage II colon cancer, the presence of LAG-3 expression on TILs was significantly associated with better 5-year DFS (HR 0.34, 95% CI 0.14–0.80, p = 0.009). The effect on DFS was mainly due to LAG-3-positive TILs in the tumor front (HR 0.33, 95% CI 0.13–0.82, p = 0.012). Conclusion: Assessment of LAG-3 might help to predict outcomes in patients with stage II colon cancer and potentially identify those patients who might benefit from adjuvant chemotherapy. Therefore, LAG-3 may serve as a prognostic biomarker in stage II colon cancer.

The emergence of immunotherapy has generated great enthusiasm in oncology improving the prognosis of pathologies such as melanoma, lung cancer, kidney cancer, bladder and head and neck cancers. This enthusiasm concerns also older patients in view of the good tolerance of immunotherapy in young people. However, advanced age is linked to changes in the immune system, called immunosenescence, which could have a negative impact on the efficacy and toxicity of immunotherapy treatment. Knowledge in terms of efficacy and tolerance is limited for geriatric patients, few being included in clinical studies. This article summarizes the experience of immunotherapy in large clinical trials. It appears that the immune checkpoint inhibitors are effective and well tolerated in the elderly.L’émergence de l’immunothérapie a engendré un grand enthousiasme en oncologie en améliorant le pronostic de pathologies telles que le mélanome et les cancers pulmonaires, rénaux, vésicaux et de la sphère ORL. Cet enthousiasme concerne aussi les patients âgés au vu de la bonne tolérance de l’immunothérapie chez les jeunes. Cependant, l’âge avancé est lié à des modifications du système immunitaire, appelées immunosénescence, qui pourraient avoir un impact négatif sur l’efficacité et la toxicité du traitement par immunothérapie. Les connaissances en termes d’efficacité et de tolérance restent limitées pour les patients gériatriques, inclus en petit nombre dans les études cliniques. Cet article résume l’expérience de l’immunothérapie dans les grands essais cliniques. Il apparaît que les inhibiteurs de points de contrôle immunitaire soient efficaces et bien tolérés chez le sujet âgé.