Friedrich Overkamp

Patient-based strategy for systemic treatment of metastatic renal cell carcinoma

There were only a few options 3 years ago to treat metastatic renal cell carcinoma (mRCC), a disease with a very poor prognosis. With the approval of targeted therapies for mRCC since December 2005, this situation has changed dramatically. Currently, oncologists can choose between several promising options to improve the longevity and quality of their patients’ lives. A widely accepted treatment scheme for targeted therapies in mRCC does not yet exist. Based on a selective literature search, drawing on studies with six targeted therapies for mRCC, and including data from the latest American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) Annual Meetings, this review introduces the available therapies, evaluates patient-specific criteria for their application and suggests an algorithm for a patient-based treatment scheme. Clinical experiences with sequential therapies are summarized and potential combination therapies discussed. In conclusion, the crucial criteria of the treatment scheme we propose are the tumor burden and the disease pace, as well as the quality of life of a patient. These define whether tumor control or tumor remission should be the primary therapeutic goal. This scheme suggests which kind of therapeutic sequence to pursue to optimize patient care in mRCC.

Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer

Background The purpose of this analysis was to assess the long-term impact of adding bevacizumab to adjuvant chemotherapy for early triple-negative breast cancer (TNBC). Methods Patients eligible for the open-label randomized phase III BEATRICE trial had centrally confirmed triple-negative operable primary invasive breast cancer (pT1a–pT3). Investigators selected anthracycline- and/or taxane-based chemotherapy for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of chemotherapy alone or with 1 year of bevacizumab (5 mg/kg/week equivalent). Stratification factors were nodal status, selected chemotherapy, hormone receptor status, and type of surgery. The primary end point was invasive disease-free survival (IDFS; previously reported). Secondary outcome measures included overall survival (OS) and safety. Results After 56 months’ median follow-up, 293 of 2591 randomized patients had died. There was no statistically significant difference in OS between treatment arms in either the total population (hazard ratio 0.93, 95% confidence interval [CI] 0.74–1.17; P = 0.52) or pre-specified subgroups. The 5-year OS rate was 88% (95% CI 86–90%) in both treatment arms. Updated IDFS results were consistent with the primary IDFS analysis. Five-year IDFS rates were 77% (95% CI 75–79%) with chemotherapy alone versus 80% (95% CI 77–82%) with bevacizumab. From 18 months after first study dose to study end, new grade ≥3 adverse events occurred in 4.6% and 4.5% of patients in the two arms, respectively. Conclusion Final OS results showed no significant benefit from bevacizumab therapy for early TNBC. Late-onset toxicities were rare in both groups. Five-year OS and IDFS rates suggest that the prognosis for patients with TNBC is better than previously thought. ClinicalTrials.gov NCT00528567

Everolimus in Metastatic Renal Cell Carcinoma after Failure of Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor (VEGFr-TKI) Therapy: Results of an Interim Analysis of a Non-Interventional Study

Background: Everolimus is approved for treatment of anti-vascular endothelial growth factor (VEGF)-refractory patients with metastatic renal cell carcinoma (mRCC). Clinical trials rarely mirror treatment reality. Thus, a broader evaluation of everolimus is valuable for routine use. Patients and Methods: A German multicenter non-interventional study documented mRCC patients starting everolimus after failure of initial VEGF-targeted therapy. Primary endpoint was effectiveness, defined as time to progression (TTP) according to investigator assessment (time from first dose to progression). Results: Of 382 documented patients, 196 were included in this interim analysis. In the efficacy population (n = 165), median TTP was 7.0 months (95% confidence interval (CI) 5.1-9.0). Among patients with < or ≥ 6 months of previous VEGF-targeted therapy, median TTP was 6.6 months (95% CI 3.8-not estimable) and 7.4 months (95% CI 4.6-9.6), respectively. Most common adverse events were anemia (13%) and dyspnea (14%). Physicians assessed high tolerance and documented high adherence to everolimus therapy (approximately 97%). Conclusion: In routine clinical practice, everolimus is effective, as measured by median TTP (longer than median progression-free survival in RECORD-1 trial), and well tolerated. Our results support everolimus use in anti-VEGF-refractory patients with mRCC.

Differenzialtherapie beim metastasierenden Nierenzellkarzinom

ZusammenfassungIm Jahr 2006 wurden Sorafenib und Sunitinib in Europa für die Behandlung von metastasierenden Nierenzellkarzinomen (mNZK) zugelassen. Weitere innovative Substanzen, über die noch keine Daten veröffentlicht wurden, sind auf dem Markt zu erwarten. Sie werden eine ganze Palette individueller therapeutischer Optionen ermöglichen. Die Grundlagen der primären chirurgischen Verfahren zur Tumor- und Metastasenresektion bleiben hierbei unberührt. Da ein anerkannter Algorithmus für diese neue Medikamentenklasse bisher fehlt, werden Empfehlungen zur mNZK-Therapie in der klinischen Praxis notwendig. Der vorgestellte Behandlungsalgorithmus basiert auf Ergebnissen der evidenzbasierten Medizin in Verbindung mit Parametern, die sich aus den im Jahr 2007 beim ASCO-Kongress vorgestellten Daten ergeben haben – und letztendlich auf breiten Erfahrungen bei der Behandlung von mNZK-Patienten.AbstractIn 2006 the new compounds Sorafenib and Sunitinib were approved in Europe for the treatment of advanced renal cell carcinoma (mRCC). Additional innovative substances are to be expected on the market for which data have not yet been published and will provide physicians with a whole array of individual therapeutic options. Principles of primary surgical procedures for tumor and metastasis resection remain untouched. An accepted algorithm for the new drug entities has, however, been missing and it is felt that recommendations on how mRCC should be treated in clinical practice are needed. The suggested treatment algorithm is based on results from evidence-based medicine together with parameters which resulted in the approval of recent data announced at the ASCO congress in 2007 and, last but not least, on wide experience in treating mRCC patients.

Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study

Background This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. Patients and methods Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. Results A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). Conclusion This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.

Adherence to Treatment Guidelines in Breast Cancer Care – a Retrospective Analysis of the ‘Organgruppe Mamma der Arbeitsgemeinschaft Gynaekologische Onkologie’

Background: The Organgruppe Mamma of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) performed a nationwide 3-phase analysis of the structure of care and standard of therapy given to patients with breast cancer from 2002 (4th quarter) to 2004 (4th quarter). The extent to which national and international treatment recommendations are implemented in routine clinical practice had so far not been evaluated in an interdisciplinary approach. No reliable data on the pattern of care of these patients have been published in Germany before. Patients and Methods: The project included early breast cancer in the adjuvant and neoadjuvant setting as well as metastatic disease. We present the results of phase III of the AGO analysis, which are based on a survey conducted by the Organkommission Mamma in the 4th quarter of 2004. Results: Evaluation of the data reveals that treatment based on the guidelines is now being implemented very reliably in certain sectors. This is of particular relevance to the pattern of adjuvant treatment in early breast cancer. In contrast, in metastatic breast cancer (MBC), the complexity of the interdisciplinary treatment approach is complicating this kind of straightforward analysis. Conclusion: The present analysis conducted by the AGO was the first attempt to analyse the treatment provided in patients presenting with MBC in a systematic fashion. The fundamental problem remains, irrespective of the stage of the tumour, that too few patients are treated in randomised clinical trials. The mission set by the AGO-Organkommission Mamma is the longitudinal observation of the therapy practices for breast cancer on the basis of the observations discussed here, which should ultimately benefit the optimisation of therapy quality in Germany.

Update Breast Cancer 2017 – Implementation of Novel Therapies

In recent years, numerous new therapy options for patients with breast cancer have been developed in clinical studies, with some options already approved for routine treatment. As the speed at which innovations are introduced increases, the importance of conferences also increases, as conferences are where the data underpinning new therapies are usually presented for the first time. This review looks at publications of the ASCO (American Society of Clinical Oncology) and ESMO (European Society of Medical Oncology) conferences in 2017, summarizes them and evaluates them in the context of existing data. The focus is on new insights for neoadjuvant therapy and new treatment options in the metastatic setting, such as the use of CDK4/6 inhibitors or PARP inhibitors. The first results of treatments with checkpoint inhibitors are presented. With the patent expiry of trastuzumab, a number of study results for trastuzumab biosimilars have also been published. The digitization of patient care provides the first results on quality of life and prognosis of patients with advanced cancer. Digital communications between patients and physicians are being evaluated in several studies in Germany. As the discussion about patient-relevant endpoints for patients in the metastatic setting continues, overall survival rates from studies of big endocrine-based therapies are urgently needed. Preliminary analyses of small study cohorts offer initial insights. In the context of improving patient care, in the coming years, questions will center on which patients particularly benefit from certain therapies and which patients need particular protection from specific side effects. Questions about these predictors are raised in many scientific projects as attention increasingly focuses on this topic.

Use of complementary and integrative medicine among German breast cancer patients: predictors and implications for patient care within the PRAEGNANT study network

PurposeThe present study aims to analyze a cohort of advanced breast cancer patients in Germany to assess their interest in complementary and alternative medicine (CAM) and patient’s use of most frequent CAM methods.Patients and methodsBased on the PREGNANT real-time breast cancer registry which is a multicenter study in Germany, questionnaires of 580 patients with advanced breast cancer were evaluated. The implemented questionnaire for CAM asked for general interest in CAM and for patient’s use of different CAM methods at present and in the past. The interest and application of CAM were analyzed for association with patients’ characteristics such as tumor, patient, and therapy characteristics.ResultsIn total, 436 out of 580 (75%) patients claimed to be interested in CAM. Further, interest in CAM is significantly correlated with younger age and absence of metastasis at the time of diagnosis. Multivariate analysis confirmed the patient’s age and distant disease status at the time of diagnosis as related to interest in CAM. A total of 56.4% of patients applied any CAM method in the past. Moreover, with increasing lines of therapies, the more frequent use of CAM was observed. Hereby, praying, vitamin supplements, and other food supplements were most frequently applied.ConclusionOur data demonstrate high overall interest and frequent use of CAM in advanced breast cancer patients supporting a strong demand of breast cancer patients for complementary counseling and treatments additional to the established cancer therapies. It is indispensable to implement counseling and evidence-based complementary treatments into clinical routine of cancer centers and to adapt postgraduate medical education, respectively.

Das ökonomische Dilemma

Die Bereitschaft von Praxen und Kliniken für ein Engagement im Bereich der Klinischen Forschung ist in den letzten 10 Jahren deutlich gestiegen. Es macht sich jedoch zunehmend Ernüchterung breit im Hinblick auf die eklatante Unterfinanzierung klinischer Studien. Der vorliegende Beitrag möchte aufgrund praktischer Erfahrungen Denkanstöße und Impulse für eine Neuorientierung der Vergütung setzen. Ursachen und Hintergründe der Unterfinanzierung werden erläutert, insbesondere werden die anfallenden Kosten eingehend dargelegt. Die Etablierung von Werkzeugen zur Kostenkalkulation erscheint dringend notwendig, erste Ansätze dazu gibt es bereits.Clinical studies have been situated very well in Germany during the last 10 years; oncologists in practices and clinics are highly motivated. However, the financing of clinical trials is desolate so that disillusionment spreads in many centers. This paper would like to give some impetus to the discussion on better and more adequate financing. Facts and backgrounds concerning unsatisfactory financing of clinical trials are demonstrated; costs are analyzed in a detailed way. It seems to be very important to establish tools for a better calculation of costs. First approaches have been defined.

Umsetzung integrativer Konzepte – eine Bestandsaufnahme

Die CAM-Beratung am Beispiel einer Patientin mit Brustkrebs Bei einer 39-jahrigen Patientin wurde aufgrund eines invasiven Mammakarzinoms eine Teilresektion der Mamma vorgenommen und anschliesend eine adjuvante Chemotherapie mit Fluoruracil, Epirubicin, Cyclophosphamid (FEC)/Paclitaxel eingeleitet. Die Patientin vertrug die Chemotherapie sehr schlecht und berichtete von anhaltender Ubelkeit, Appetitlosigkeit und starkem Gewichtsverlust von insgesamt 8 kg Korpergewicht sowie Schleimhautentzundungen, Depression und Fatigue. Sie erwog deshalb, die Therapie nach 2 Therapiezyklen abzubrechen, sofern sich die Vertraglichkeit nicht durch weitere, bisher nicht genutzte Masnahmen – namentlich eine Misteltherapie – deutlich verbessern liese. Wahrend ihr behandelnder Onkologe dezidiert von einer begleitenden Misteltherapie abgeraten hatte, war ihr von einem telefonischen Beratungsdienst empfohlen worden, die Chemotherapie abzubrechen und eine rein komplementarmedizinische Nachbehandlung vornehmen zu lassen. In dieser belastenden Situation suchte sie unsere Beratungsstelle auf und bat um sachliche Information und Unterstutzung. Die Frage nach dem Nutzen der Mistel insbesondere bei Brustkrebs ist durchaus berechtigt. Gemas Cochrane Review zur Misteltherapie, der auf einer Auswertung von 21 prospektiv-randomisierten Studien (davon 7 bei Mammakarzinom) beruht, gibt es Hinweise, dass die Misteltherapie sich uberwiegend gunstig auf bestimmte Aspekte der Lebensqualitat Integrative Onkologie im Kontext eines universitaren Cancer Centers Verantwortlicher Autor: Matthias Rostock, Hamburg