SummaryScoring systems for classifying genomic alterations (GAs) with respect to their potential targeted anticancer therapies (TTs) may be useful for rational and evidence-based decision-making, for example in molecular tumor boards. Therefore, a working group of the European Society for Medical Oncology (ESMO) has developed a comprehensive and reproducible classification score that allows the ranking of GAs and TTs according to their level of evidence and clinical relevance. This score is called the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Another score not explicitly developed for TTs but helpful in grading novel TTs is the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). This tool was designed to objectively quantify the clinical benefit of novel approved therapies. The current review summarizes the status quo of these scores and their applicability for molecular tumor boards.
The mTOR‐inhibitor everolimus has been approved for the treatment of advanced neuroendocrine tumors (NETs) but is associated with relevant toxicities in clinical practice. Hence, optimal treatment sequencing and the impact of dose reductions have yet to be clarified. This retrospective analysis assessed patients with advanced, well‐differentiated NET treated with everolimus at the Medical University of Vienna. The primary objective was to evaluate the efficacy of everolimus in a real‐world cohort. A total of 52 patients treated with everolimus for advanced NET grade 1 (G1) or G2 (or typical or atypical carcinoid) 2010–2021 were included in this analysis. The most common sites of origin were pancreas (44%) and lung (29%). The initial dose was decided by the treating physician based on clinical assessment and 25 patients (48%) each were started at 10 mg/day and 5 mg/day. Median progression‐free survival (PFS) following everolimus in the overall cohort was 9.8 months (95% CI: 4.3–15.3), with a statistically significant PFS difference (p = .03) between NET G1/typical carcinoids (42.9 months) and NET G2/atypical carcinoids (8.9 months). PFS was numerically but not significantly shorter in patients treated with a reduced dose (7.5 months vs. 12.4 months, p = .359). Even in this mixed full/half dose cohort, 93% developed treatment‐related side effects (mostly grade I, no grade IV), 63% had dose reductions or interruptions, and five stopped due to toxicity. Median survival following treatment was 40.9 months (95% CI: 21.5–60.3) and no difference with regard to dosing was observed (p = .517). These data from an unselected patient cohort show long‐term outcomes similar to those reported in the pivotal studies. Comparing everolimus starting dose, median PFS did not significantly differ for patients treated at a lower dose. While this finding is limited by the sample size and warrants prospective verification, initiating therapy at a reduced dose might be practicable and safe in a distinct subset of patients.
Background: Different oncological therapies have been approved for small intestinal neuroendocrine tumors (SI-NETs), but relatively little is known about efficacy and long-term outcome outside of phase III trials. Methods: This retrospective analysis assessed patients with well-differentiated, metastatic SI-NETs treated at the Medical University of Vienna, an approved European Neuroendocrine Tumor Society (ENETS) Center of Excellence for neuroendocrine tumors. The primary objective was to assess progression-free survival (PFS) following approved therapies, that is, octreotide, lanreotide, peptide receptor radionuclide therapy (PRRT), and everolimus, in a representative real-world collective. Results: A total of 77 patients receiving systemic treatment for advanced SI-NETs between 2010 and 2021 were included, with a median follow-up time of 82.3 months [95% confidence interval (CI), 57.8–106.8 months]. In the entire collective, the estimated median PFS following first-line therapy was 32.0 months (95% CI, 23.5–40.5 months). Peritoneal carcinomatosis was significantly associated with worse PFS ( p = 0.016). Regarding therapeutic strategies and outcome, 59 patients received somatostatin analogs first line and no significant difference in PFS was observed between lanreotide and octreotide (29.3 versus 35.5 months, p = 0.768). Across all treatment lines, 42 patients underwent PRRT (estimated median PFS: 32.0 months; 95% CI, 25.6–38.3 months) and a small subgroup of 7 patients received everolimus (estimated median PFS: 9.2 months; 95% CI, 1.6–17.0 months). For the total cohort, the estimated median OS following first-line therapy was 100.6 months (95% CI, 82.3–118.8 months), but the high proportion of deaths attributed to NET (77.8%) underlines the lethal nature of the disease. No unexpected toxicities were observed. Conclusions: While peritoneal carcinomatosis emerged as an adverse prognostic factor for PFS in this collective, the long-term outcome of patients treated at a specialized NET center using approved therapies appeared comparable to pivotal studies in SI-NET.
SummaryEstablished systemic treatment options for advanced thyroid cancer include the multityrosine kinase inhibitors lenvatinib and sorafenib for radioactive iodine refractory differentiated thyroid cancer (DTC) and vandetanib and cabozantinib for medullary thyroid cancer (MTC). Recently, the COSMIC-311 study resulted in approval of cabozantinib for DTC with progression upon lenvatinib and/or sorafenib; thus, for the first time a specific second-line therapy has been defined for these patients. In addition, the therapeutic landscape of thyroid cancer has been expanded by targeted therapies based on molecular tumor profiles. Selective RET inhibitors such as selpercatinib and pralsetinib show high activity in DTC with RET fusions and MTC with RET mutations, respectively. Further targeted treatment options include NTRK inhibitors for thyroid cancers with NTRK fusions and BRAF-targeted therapy for BRAF V600E-mutated (anaplastic) thyroid cancer.
Brain metastases (BM) in patients with thyroid cancer (TC) are rare with an incidence of 1% for papillary and follicular, 3% for medullary and up to 10% for anaplastic TC (PTC, FTC, MTC and ATC). Little is known about the characteristics and management of BM from TC. Thus, we retrospectively analyzed patients with histologically verified TC and radiologically verified BM identified from the Vienna Brain Metastasis Registry. A total of 20/6074 patients included in the database since 1986 had BM from TC and 13/20 were female. Ten patients had FTC, 8 PTC, one MTC and one ATC. The median age at diagnosis of BM was 68 years. All but one had symptomatic BM and 13/20 patients had a singular BM. Synchronous BM at primary diagnosis were found in 6 patients, while the median time to BM diagnosis was 13 years for PTC (range 1.9–24), 4 years for FTC (range 2.1–41) and 22 years for the MTC patient. The overall survival from diagnosis of BM was 13 months for PTC (range 1.8–57), 26 months for FTC (range 3.9–188), 12 years for the MTC and 3 months for the ATC patient. In conclusion, development of BM from TC is exceedingly rare and the most common presentation is a symptomatic single lesion. While BM generally constitute a poor prognostic factor, individual patients experience long-term survival following local therapy.
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