memo - Magazine of European Medical Oncology

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Molecular profiling in breast cancer—ready for clinical routine?

Tendl, Kristina A.; Bago-Horvath, Zsuzsanna

2020 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-020-00578-0

SummaryThe herald of genomic testing opened novel diagnostic and therapeutic possibilities for many tumor entities. For breast cancer, molecular profiling has become an integral part of disease management on multiple levels. Genetic testing allows for the identification of hereditary cancer syndromes in patients with a family history of malignancies and contributes to the successful prevention of breast cancer. In early breast cancer, several prospective randomized trials demonstrated the prognostic significance of commercially available mRNA-based gene expression analyses, which now have become part of standard of care in the adjuvant setting. In advanced breast cancer, testing for targetable mutations ensures personalized cancer treatment. Poly-ADP-ribose polymerase (PARP) inhibitors provide the first targeted alternative for patients with BRCA 1/2-associated breast cancer. In advanced breast cancer of luminal type, the detection of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutations provides a novel treatment option with alpelisib, a PIK3CA inhibitor. Further targetable mutations include NTRK3 in rare cases of secretory breast carcinoma and human epidermal growth factor receptor 2 (HER2). Recent data support the importance of the analysis of circulating tumor cells and cell-free DNA. These “liquid biopsies” open novel possibilities of molecular profiling. However, clinical benefit of such analyses remains to be confirmed.
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Current state and perspectives of checkpoint inhibitors in ovarian cancer treatment

Bartl, Thomas; Paspalj, Valentina; Polterauer, Stephan; Grimm, Christoph

2020 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-020-00579-z

SummaryThe introduction of checkpoint inhibitors (CPI) has set a paradigm shift within the therapies for a variety of advanced solid tumors. By altering key regulators of cellular immune response, so-called immune checkpoints, CPIs modulate peripheral cancer immune tolerance to induce cancer-targeted immune reactions. Response rates, however, vary significantly between different solid tumor types. A certain efficacy of CPIs has been described for gynecological malignancies, as the KEYNOTE-028 study reported an objective response rate (ORR) of 13.0% (95% confidence interval [CI] 2.8–33.6) for endometrial and the CheckMate-358 study an ORR of 26.3% (95% CI 9.1–51.2) for cervical cancer. With respect to epithelial ovarian cancer (EOC), recent evidence suggests only modest response, as the largest study to date by Matulonis et al. reported in 2019 that pembrolizumab induced an ORR of only 8.0% in 376 patients with EOC. Thus, latest clinical data indicate EOC to be rather “immunologically cold”, most likely due to both an inherently low tumor mutational burden (TMB) and a subsequently limited cellular antigen presentation. As CPI monotherapy therefore seems to be of limited clinical significance, ongoing clinical trials moved to combine CPI with PARP inhibitors and/or with antiangiogenic agents to elucidate possible synergistic antitumoral effects of these combinations. Despite promising preliminary data, the large phase 3 trials are still ongoing. To date, CPI monotherapy in OC remains highly experimental and is only to be administered within clinical studies and a highly selected group of patients.
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PLATON: use of romiplostim to treat chronic primary immune thrombocytopenia

Mihaylov, Georgi; Skopec, Barbara; Sninska, Zuzana; Tzvetkov, Nikolai; Cerna, Olga; Ivanushkin, Vladlen; Niepel, Daniela; Björklöf, Katja; Černelč, Peter

2020 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-020-00580-6

SummaryChronic primary immune thrombocytopenia (ITP) is an autoimmune disease involving the formation of antibodies to thrombocytes, leading to increased platelet destruction and chronic thrombocytopenia. Additionally, impaired platelet production is due to relative thrombopoietin deficiency. Romiplostim, a thrombopoietin receptor agonist, normalized platelet counts in affected patients in randomized controlled trials and real-world observational studies. The present study collected real-world practice data from Central and Eastern Europe, i.e. Slovakia, Slovenia, Bulgaria, Russia, and Czech Republic, between December 2010 and July 2017. This was an ambidirectional observational, noninterventional cohort study within the approved romiplostim indication. One-hundred patients were analyzed. Prior to romiplostim start, 98% had received other ITP medications and, in the prior 6 months, 40% had experienced bleeding events. Romiplostim was started 1.92 years (median) after ITP diagnosis. The median mean on-study dose was 2.62 µg/kg/week. During romiplostim treatment, platelet counts rapidly normalized to >50 × 109/L, 20% of patients experienced bleeding events (none grade 3/4), and 13% required splenectomy. At the end of study, 25% of patients were in remission. One patient experienced serious adverse drug reactions (thrombosis, dysphagia), none were fatal. In conclusion, romiplostim dosing, effectiveness and safety in these unselected ITP patients seemed comparable with observations in clinical trials and similarly designed observational studies.
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The role of pathology in sarcoma

Liegl-Atzwanger, Bernadette

2020 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-020-00574-4

SummarySoft tissue sarcomas are exceedingly rare cancers with more than 100 different histiologic subtypes and tremendous morphologic heterogeneity. Next generation sequencing (NGS) techniques have drastically improved our knowledge about these tumours. The possibility to use these techniques routinely changed the diagnostic standards in soft tissue pathology. Within the last few years pathologists were confronted with a growing number of exceedingly rare, partly molecularly defined, tumour entities. The proposed pathologic diagnosis dictates prognosis and treatment. Therefore, specialized soft tissue pathology units with the possibility to include molecular diagnostics into a histopathological report for diagnostic, predictive and prognostic aspects are needed. A second opinion by a soft tissue pathologist, before final treatment decision, should be mandatory to ensure optimal treatment for all patients by a multidisciplinary team in a specialized centre.
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