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Hutterer, Georg C.; Pichler, Martin
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00798-6
Summary In this short review article we discuss three key oral presentations from the European Society for Medical Oncology (ESMO) Congress 2021 concerning localised, as well as advanced/metastatic renal cell carcinoma, highlighting their potential implications for the improvement of therapeutic modalities in affected patients. (1) Conditional survival and 5‑year follow-up of CheckMate 214 currently represent the longest available phase III follow-up data in the first-line (combination) treatment of clear cell renal cell carcinoma patients with nivolumab + ipilimumab vs. sunitinib. This analysis demonstrated durable efficacy benefits with the respective combination vs. sunitinib. Moreover, conditional survival results predict an increased probability of durable overall survival, progression-free survival, and response rates with nivolumab + ipilimumab at 2‑ and 3‑year landmarks. (2) The randomised, double-blind, phase III KEYNOTE-564 study, presented as a highlight late-breaking abstract at the ASCO Congress 2021, met its primary endpoint of disease-free survival with post nephrectomy adjuvant pembrolizumab vs. placebo in clear cell renal cell carcinoma patients. At ESMO 2021, the authors presented patient-reported outcomes, whereby no clinically meaningful changes from baseline in health-related quality of life or symptom scores were observed with adjuvant pembrolizumab or placebo. These findings suggest that adjuvant pembrolizumab was tolerable from a patient perspective. (3) A phase II prospective trial of frontline cabozantinib in metastatic collecting ducts carcinoma, namely the BONSAI trial (Meeturo 2), met its primary endpoint objective response rate, showing promising efficacy and acceptable tolerability of cabozantinib in respective patients. Since metastatic collecting ducts carcinoma is biologically poorly characterised and heavily underrepresented in prospective randomised trials, BONSAI gains particular importance.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00801-0
Summary The following three abstracts presented at EESMO 2021 highlight three different areas of therapeutic strategies for non small cell lung cancer. First, neoadjuvant Atezolizumab managed to show a superior DFS compared to best supportive care in completely resected NSCLC stage II–IIIA. Second, Cemiplimab combined with chemotherapy reached the primary endpoint of OS compared to chemo alone in advanced stage IIIB/C & stage IV NSCLC patients. Third, the BEVERLY trial showed that the combination of Erlotinib with Bevacizumab in advanced EGFR-mutated NSCLC prooved to be superior to Erlotinib monotherapy in the current/former smoker subgroup, suggesting that this subgroup represents a differnt tumor biology with sprecial therapeutic needs.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00810-zpmid: 35540707
Summary The congress of the European Society of Medical Oncology (ESMO) that recently took place virtually was marked by highlights in many different cancer types. New therapeutic options especially in metastatic breast cancer will hopefully bring a longer life to thousands of patients all over the world. These include new antibody–drug conjugates (ADCs) and checkpoint inhibitors as well as cyclin-dependent kinase (CDK)4/6 inhibitors prolonging overall survival. In Her2-positive advanced breast cancer trastuzumab deruxtecan (T-DXd) compared to trastuzumab emtansine showed a superior benefit in progression-free survival (PFS) in patients who received at least one prior therapy line in the metastatic setting. In the first-line treatment of metastatic triple-negative breast cancer, an overall survival (OS) benefit of pembrolizumab plus chemotherapy versus chemotherapy alone was confirmed for patients with a combined positive score (CPS) ≥ 10. Final results of MONALESSA‑2 demonstrated a great OS benefit for the cyclin dependent kinase (CDK)4/6 inhibitor ribociclib plus endocrine therapy as first-line treatment of patients with hormone receptor (HR)-positive, Her2-negative breast cancer.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00808-7pmid: 35505999
Summary This short review reflects on a personal selection of three abstracts on colorectal cancer (CRC) presented at the 2021 ESMO Congress: (1) KRASG12C as a new therapeutic target in metastatic CRC, supported by data from the KRYSTAL‑1 and CodeBreaK101 trials, (2) positive phase 3 data on the possible role of selective internal radiotherapy (SIRT) in the second-line treatment of liver-limited metastatic CRC, and (3) the impact of the coronavirus disease 2019 (COVID-19) pandemic on CRC screening, management and mortality, now and in the upcoming years.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00799-5
Summary The treatment of breast cancer is constantly evolving, making it hard for oncologists to be up-to-date with all aspects of the disease. Guidelines summarizing the current treatment standard for different clinical scenarios may be used to overcome these challenges. There are several guidelines that can be used in clinical practice: The NCCN guidelines, most widely known around the world, are very up-to-date and cover all treatment options for a wide range of scenarios using decision trees. The German S3-guidelines are text-based and include levels of evidence and grades of recommendation. Those of the German ‘Arbeitsgemeinschaft für Gynäkologische Onkologie‘ (AGO) in addition provide short summaries of recent publications to support the recommendations. The St. Gallen recommendations for early breast cancer are consensus-based and very interdisciplinary. And finally, the ESMO guidelines for advanced breast cancer most recently include the ESMO Scale for a Actionability of Molecular Targets (ESMO-ESCAT), which helps in deciding which molecular test to use with respect to treatment decisions. Most guidelines are very up-to-date and may be a helpful in clinical decision-making. However, one should never forget that the complexity of clinical scenarios goes beyond the factors that can be mapped in guidelines. This also includes, for example, age, comorbidities and, last but not least, our patients’ preferences.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00804-xpmid: 35437451
Summary The treatment landscape of chronic lymphocytic leukemia (CLL) has undergone profound change in recent years. Targeted therapies have outnumbered chemotherapy-based treatment approaches demonstrating superior efficacy and tolerability profiles across nearly all CLL patient subgroups in the frontline and relapsed disease treatment setting. Individual selection of these novel agents is rather driven by patients’ comorbidities and personal preferences than fitness and age. Given the high amount of currently licensed novel agents in both treatment-naïve as well as relapsed CLL patients and currently limited evidence from comparative clinical trials, clinicians sometimes appear spoilt for choice when selecting optimal therapy. This short review discusses recent clinical trial data focusing on treatment with targeted drugs and aims to help guide CLL treatment selection in individual patients.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-021-00780-8
Summary Antibody–drug conjugates (ADCs) are a relatively new class of highly potent molecules which combine the targeting properties of monoclonal antibodies with the cell destructive properties of cytotoxic agents in order to reduce systemic exposure and toxicity of the latter. Gemtuzumab–ozogamicin was the first-in-class drug approved by the US Food and Drug Administration (FDA) in 2000, but later approval was withdrawn. In the meantime, the number of these types of drugs available for clinical use is rapidly evolving. This review gives a brief overview of currently approved ADCs, with special consideration of pharmaceutical aspects
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-021-00781-7
Summary Antibody–drug conjugates (ADCs) against numerous molecular targets are currently being developed for the treatment of breast cancer (BCa). While the first ADC directed against Her2, namely trastuzumab–emtansine, was approved several years ago, targeting of TROP‑2, an epithelial cell marker overexpressed in approximately 80% of triple-negative breast cancers (TNBC) has gained interest through positive clinical data reported for the compound sacituzumab–govitecan (SG) resulting from the phase 3 ASCENT trial. This short review summarizes the data that led to approval of SG and to take a closer look at the state of clinical development of other ADCs targeting TROP‑2 in TNBC.
Mayrhofer, Karl; Niedersüß-Beke, Dora
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-021-00782-6
Summary New agents and combinations continue to change the clinical practice of treating patients with renal cell carcinoma. In this review we want to highlight the most recent therapeutic developments and also give an overview of the current standard of care in advanced disease. Studies investigating lenvatinib plus pembrolizumab, belzutifan and cabozantinib are discussed.
Feichtner, Andreas; Kugler, Valentina; Schwaighofer, Selina; Nuener, Thomas; Fleischmann, Jakob; Stefan, Eduard
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-021-00790-6pmid: 35677701
Summary Numerous kinases act as central nodes of cellular signaling networks. As such, many of these enzymes function as molecular switches for coordinating spatiotemporal signal transmission. Typically, it is the compartmentalized phosphorylation of protein substrates which relays the transient input signal to determine decisive physiological cell responses. Genomic alterations affect kinase abundance and/or their activities which contribute to the malignant transformation, progression, and metastasis of human cancers. Thus, major drug discovery efforts have been made to identify lead molecules targeting clinically relevant oncokinases. The concept of personalized medicine aims to apply the therapeutic agent with the highest efficacy towards a patient-specific mutation. Here, we discuss the implementation of a cell-based reporter system which may foster the decision-making process to identify the most promising lead-molecules. We present a modular kinase conformation (KinCon) biosensor platform for live-cell analyses of kinase activity states. This biosensor facilitates the recording of kinase activity conformations of the wild-type and the respective mutated kinase upon lead molecule exposure. We reflect proof-of-principle studies demonstrating how this technology has been extended to profile drug properties of the full-length kinases BRAF and MEK1 in intact cells. Further, we pinpoint how this technology may open new avenues for systematic and patient-tailored drug discovery efforts. Overall, this precision-medicine-oriented biosensor concept aims to determine kinase inhibitor specificity and anticipate their drug efficacies.
Sharie, Ahmed H. Al; Zu’bi, Yazan O. Al; Sharie, Sarah Al; Baydoun, Hawra A.; Atawneh, Farah H.; Alshari, Osama; Albals, Dima
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-021-00789-zpmid: 35096191
Summary Introduction Systemic capillary leak syndrome (SCLS) is a rare and often fatal clinical entity used to describe a generalized increase in vascular permeability leading to fluid extravasation toward the interstitial compartment. SCLS could be an idiopathic disease or secondary to infections, malignancies or drugs. Case We present a case of presumably granulocyte colony-stimulating factor (G-CSF)-induced SCLS in a 21-year-old man diagnosed with T‑lymphoblastic leukemia/lymphoma. He received the 6th cycle (part B) of the hyper-CVAD chemotherapeutic regimen followed by the initiation of neutropenic fever prophylaxis protocol which included antibiotics and G‑CSF. In a course of hours, the patient became dyspneic, hypotensive, and edematous which required intensive care unit admission and was stabilized accordingly. In the following days the patient’s anasarca progressively increased which was associated with hypoalbuminemia, hypotension and anemia with pericardial and bilateral plural effusions. As a diagnosis of exclusion augmented by the acuity of such clinical event, observed concomitantly with the administration of the prophylaxis protocol, the suspicion of G‑CSF-induced SCLS was established. Consequently, G‑CSF was discontinued and treatment with dexamethasone and intravenous immunoglobulins (IVIG) was started. The patient’s condition improved significantly illustrated by hemodynamic stability in addition to improvement regarding the anasarca, hypoalbuminemia, and anemia. Follow-up scans suggest resolution of the pericardial and plural effusions. Conclusion SCLS remains a serios and potentially fatal complication of G‑CSF administration which should be taken into consideration, since such medication is widely utilized in oncology wards.
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-021-00719-zpmid: 34149939
Summary The outbreak of coronavirus disease 2019 (COVID-19) has put health systems worldwide under great pressure on numerous levels. COVID-19 is a heterogeneous situation where some people experience mild symptoms for which no serious intervention is needed, while others may experience serious situations ranging from acute respiratory distress syndrome (ARDS) or even respiratory failure and end organ damage. Serious COVID-19 cases may be complicated with a cytokine storm caused by hemophagocytic lymphohistocytosis, which is a life-threatening situation. Efforts should be directed to reveal accompanying diseases that may trigger the cytokine storm. Early diagnosis leads to a better understanding of how to deal with this emergency status; however, even with early intervention, outcomes are still very poor.
Udovica, Simon; Müser, Nino; Pechlaner, Agnes; Reichinger, Andreas; Aichinger, Christoph; Strasser-Weippl, Kathrin; Rumpold, Holger; Petzer, Andreas; Wöll, Ewald; Hilbe, Wolfgang; Müldür, Ercan
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00814-9
Summary Background Various registries of patients with cancer and coronavirus disease 2019 (COVID-19) emerged over the last few months and patients with cancer are reported to be at increased risk for severe outcome of COVID-19. Yet, many studies lack a direct control group and include patients with different baseline parameters. Here we report data for patients with active malignancy who were hospitalized for severe COVID-19 and a control group hospitalized with severe COVID-19, but not diagnosed with ongoing malignant disease. Moreover, we incorporate the prognostic 4C Mortality Score which estimates in-hospital mortality for COVID-19 patients. Methods In all, 245 patients hospitalized with severe COVID-19 between March 2020 and March 2021 were included in the analysis. Among those, 89 patients were diagnosed with active malignancy. Primary endpoint was COVID-19-associated mortality. Results COVID-19-associated mortality was significantly higher in cancer patients than in the control group (46.1 vs. 27.6%, odds ratio [OR] 2.56, p < 0.001). In multivariable analysis, diagnosis of active malignancy (OR 4.59) and poor ECOG status ≥ 3 (OR 6.56) were the strongest predictors of COVID-19-related death. The prognostic 4C Mortality Score correctly predicted mortality in the control group (occurred: 27.6%, vs. estimated: 27.3%, p > 0.999), but significantly underestimated COVID-19-related mortality in cancer patients (occurred: 46.1% vs. estimated: 32.2%, p = 0.003). Conclusion Active malignancy was associated with high mortality in patients with severe COVID-19 during the first period of the COVID-19 pandemic. The mortality rate was underestimated by the 4C Mortality Score.
Udovica, Simon; Strasser-Weippl, Kathrin; Fischer, Eva; Niedersüß-Beke, Dora
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00805-w
Summary Neurotoxicity is a rare but often fatal immune-related adverse event (irAE). Here we report the case of a 73-year-old woman treated with pembrolizumab for metastatic bladder cancer who developed aseptic meningoencephalitis after two courses of immunotherapy. Cranial magnetic resonance imaging (cMRI) showed disseminated dot-like lesions in the terminal vascular bed of both hemispheres suggesting aseptic meningitis or vasculitis. No infectious cause could be identified in cerebrospinal fluid (CSF) cultures and polymerase chain reaction (PCR) analyses. She was treated with high-dose steroids and pre-emptive antiviral/antibiotic therapy. The patient died 6 days after onset of symptoms.
Mutschlechner, Beatrix; Dertinger, Susanne; Offner, Felix; Buck, Veronika; Becherer, Alexander; Gasser, Klaus; Hartmann, Bernd; Winder, Thomas
2022 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-022-00806-9
Summary Immunotherapy is the first-line treatment in many solid cancers. Immune system activation leads to specific immune-related adverse events (irAE), which also include the rare sarcoid-like reaction (SLR). In imaging studies SLR can mimic cancerous lesions. Even though patients suffering from SLR are mostly asymptomatic and do not need antisarcoidosis therapy, it is crucial to not misdiagnose irAE as disease progression and unnecessarily discontinue vital immunotherapy. However, SLR should be considered at any point if disease progression is suspected. In addition, the diagnosis of SLR can only be confirmed histologically. In this case report, we want to highlight the clinical relevance of recognizing SLR in a patient with advanced melanoma treated with nivolumab and emphasize the importance of rebiopsy in case of suspected disease progression.