A rational two-step approach to KRAS mutation testing in colorectal cancer using high resolution melting analysis and pyrosequencing

HRM analysis of NRAS codon 61. (TIF 553 kb

Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer A Phase 1 and Randomized Phase 2 Trial

Importance: ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life. Objective: To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients with mBC (phase 2). Design, setting, and participants: The MTD in phase 1 was assessed using a 3 + 3 design with capecitabine dose modification. Phase 2 was an open-label, randomized, international multicenter study of patients with mBC treated with T-DM1 plus capecitabine or T-DM1 alone. Eligible patients had previously treated ERBB2-positive mBC or LA/mGC with no prior chemotherapy treatment for advanced disease. Interventions: Patients in the phase 1 mBC cohort received capecitabine (750 mg/m2, 700 mg/m2, or 650 mg/m2 twice daily, days 1-14 of a 3-week cycle) plus T-DM1 3.6 mg/kg every 3 weeks. Patients with LA/mGC received capecitabine at the mBC phase 1 MTD, de-escalating as needed, plus T-DM1 2.4 mg/kg weekly. In phase 2, patients with mBC were randomized (1:1) to receive capecitabine (at the phase 1 MTD) plus T-DM1 or T-DM1 alone. Main outcomes and measures: The phase 1 primary objective was to identify the MTD of capecitabine plus T-DM1. The phase 2 primary outcome was investigator-assessed overall response rate (ORR). Results: In phase 1, the median (range) age was 54.0 (37-71) and 57.5 (53-70) years for patients with mBC and patients with LA/mGC, respectively. The capecitabine MTD was identified as 700 mg/m2 in 11 patients with mBC and 6 patients with LA/mGC evaluable for dose-limiting toxic effects. In phase 2, between October 2014 and April 2016, patients with mBC (median [range] age, 52.0 [28-80] years) were randomized to receive combination therapy (n = 81) or T-DM1 (n = 80). The ORR was 44% (36 of 81 patients) and 36% (29 of 80 patients) in the combination and T-DM1 groups, respectively (difference, 8.2%; 90% CI, -4.5 to 20.9; P = .34; clinical cutoff, May 31, 2017). Adverse events (AEs) were reported in 78 of 82 patients (95%) in the combination group, with 36 (44%) experiencing grade 3-4 AEs, and 69 of 78 patients (88%) in the T-DM1 group, with 32 (41%) experiencing grade 3-4 AEs. No grade 5 AEs were reported. Conclusions and relevance: Adding capecitabine to T-DM1 did not statistically increase ORR associated with T-DM1 in patients with previously treated ERBB2-positive mBC. The combination group reported more AEs, but with no unexpected toxic effects

Key aspects of psychosocial needs in palliative care - a qualitative analysis within the setting of a palliative care unit in comparison with specialised palliative home care

Abstract Background The number of palliative care patients with complex needs is increasing in developed countries. In addition to physical aspects and symptom control, psychosocial aspects are of great importance for palliative care patients. The aim of this study was to understand which psychosocial aspects are important to patients, relatives and health professionals within the setting of a palliative care unit in comparison with specialised palliative home-care (SPHC). Methods We used a qualitative design based on semistructured interviews, which were coded via qualitative content analysis. The study took place in the state of Hesse, Germany, and data collection was conducted in 2017 (interviews from the ELSAH study, which was conducted in a SPHC) and 2018 (supplementary interviews conducted in a palliative care unit). The results from both settings were compared. Results In the palliative care unit, 10 health professionals, 11 patients and 8 relatives were interviewed. In the outpatient setting, we interviewed 30 health professionals, 14 patients and 14 relatives. We identified four key psychosocial issues related to palliative care that were relevant in both the inpatient and outpatient settings: care planning, patient-centred care, a protected environment with feelings of safety, and psychological well-being. In addition, immediate availability of medical staff, greater relief of the relatives and better accessibility of psychological care were more important in the inpatient setting than in the specialised palliative home care setting. Conclusions Knowledge and application of the identified key issues may improve patient-centred palliative care. Accessibility of psychological care and immediate availability of medical staff may be important factors for enhancing psychological well-being in the inpatient palliative care setting. Consideration of the identified key issues may help to develop more collaborative transitions between the palliative care unit and the SPHC and may help to provide palliative care patients and their families with care that is appropriate and feasible for them. Trial registration The underlying comparative study of the outpatient setting of specialised palliative home-care (ELSAH) was registered within the German Clinical Trials Register DRKS-ID: DRKS00012421, ( https://drks.de/search/de/trial/DRKS00012421 ) on 19th May 2017

Collaborative advance care planning in advanced cancer patients: col-ACP –study – study protocol of a randomised controlled trial

Background: To assure patient-centred end-of-life care, palliative interventions need to account for patients' preferences. Advance care planning (ACP) is a structured approach that allows patients, relatives and physicians to discuss end-of-life decisions. Although ACP can improve several patient related outcomes, the implementation of ACP remains difficult. The col-ACP-study (collaborative advance care planning) will investigate a new ACP procedure (col-ACP-intervention (German: Hand-in-Hand-Intervention)) in palliative cancer patients and their relatives that addresses individual values and targets barriers of communication before an ACP process. Methods: In a randomised controlled trial, 270 cancer patients without curative treatment options and their relatives will receive either 1) col-ACP 2) a supportive intervention (active control group) or 3) standard medical care (TAU). col-ACP comprises two steps: a) addressing various barriers of patients and relatives that discourage them from discussing end-of-life issues followed by b) a regular, structured ACP procedure. The col-ACP-intervention consists of 6 sessions. Primary endpoint is the patients' quality of life 16 weeks after randomisation. Secondary endpoints include measurements of distress; depression; communication barriers; caregivers' quality of life; existence of ACP or advance directives; the consistence of end of life care; and others. Patients will be followed up for 13 months. Multivariate analyses will be carried out. Qualitative evaluation of the intervention will be conducted. Discussion: Augmentation of a regular ACP program by a structured psycho-oncological intervention is an innovative approach to target barriers of communication about end-of-life issues. Study findings will help to understand the value of such a combined intervention in palliative care

Cancer patient utilisation of psychological care in Germany : The role of attitudes towards seeking help

OBJECTIVE Even if significantly distressed, many patients with cancer do not seek psychological help. There is growing evidence that attitudes are central barriers for help-seeking, and instruments to assess cancer patients' attitudes towards help-seeking are urgently needed. This study aimed to evaluate the German Attitudes towards Seeking Help after Cancer Scale (ASHCa-G) and investigated the relationship between patients' attitudes and psychological care utilisation. METHODS The ASHCa-G was presented to 270 patients with cancer (age 63.0~±~12.7~years, 44.8% women). Item analyses, principal component analysis and associations with age, social support, help-seeking intention and psychological care utilisation were calculated. A hierarchical logistic regression was performed to ascertain the leading role of attitudes in explaining psychological care utilisation. RESULTS Principal component analysis supported a two-component solution, which showed good internal consistency for the positive attitudes (eka~=~0.80) and negative attitudes (eka~=~0.75) subscales. The associations with age, distress and help-seeking intention confirmed the validity of the ASHCa-G. Positive attitudes explained most variance of cancer patients' current psychological care utilisation. CONCLUSION The ASHCa-G seems to be a reliable and valid questionnaire for assessing attitudes towards seeking psychological help among patients with cancer. Clinical practice might profit from identifying attitudinal barriers that hinder patients with cancer from seeking psychological help

First‐line nab‐paclitaxel plus carboplatin for patients with advanced non‐small cell lung cancer: results of the NEPTUN study

Abstract Background Platinum‐based chemotherapy remains a first‐line standard of care for approximately 30% of patients with non‐small cell lung cancer (NSCLC) not harboring a druggable alteration. Favorable efficacy and safety of the nab‐paclitaxel/carboplatin (nab‐P/C) combination was shown in the pivotal phase 3 trial. However, information on effectiveness of nab‐P/C in a real‐world setting in Germany is missing. The NEPTUN study prospectively investigated the effectiveness and safety of nab‐P/C in patients with advanced NSCLC in a real‐world setting. Methods Patients with advanced or metastatic NSCLC received first‐line nab‐P/C according to clinical routine. The primary endpoint was 6‐month progression‐free survival rate (PFS6). Other endpoints included further effectiveness parameters, safety and quality of life. Data were analyzed descriptively. Results 408 patients were enrolled. PFS6 was 40.8% (95% confidence interval [CI], 35.3–46.2); median PFS was 5.2 months (95% CI, 4.5–5.7). overall response rate was 41.5% (95% CI, 36.3–46.8). Median overall survival (OS) was 10.5 months (95% CI, 9.2–11.6). Subgroup analyses revealed median OS for squamous versus non‐squamous histology (11.8 months [95% CI, 9.2–13.8] vs. 9.6 months [95% CI, 7.7–11.2]) and age ≥70 versus <70 years (11.7 months [95% CI, 9.4–14.3] vs. 9.6 months [95% CI, 7.5–11.2]). Most common treatment‐emergent adverse events (TEAEs) were anemia (26.5%), leukopenia (25.7%), and thrombocytopenia (16.6%). Mostly reported grade 3/4 TEAEs were leukopenia (10.2%), anemia (8.6%), and pneumonia (5.1%). nab‐paclitaxel‐related deaths as reported by the investigator occurred in 0.8% of patients. Conclusion These real‐world data support the effectiveness and safety of nab‐P/C as first‐line treatment for patients with advanced NSCLC independent of tumor histology. The results are comparable with the pivotal phase 3 trial. No new safety signals emerged