Onkozentrum Dresden

Patients with lung cancer under treatment have been associated with a high risk of COVID-19 infection and potentially worse outcome, but real-world data on patient-reported outcomes (PROs) are rare. We assess patients' characteristics and PROs before and during the COVID-19 pandemic in an advanced non-small cell lung cancer (NSCLC) cohort in Germany. Patients with locally advanced or metastatic NSCLC from the prospective, multicentre, observational CRISP Registry (NCT02622581) were categorised as pre-pandemic (March 2019 to Feb 2020, n = 1621) and pandemic (March 2020 to Feb 2021, n = 1317). From baseline to month 15, patients' health-related quality of life (HRQoL) was assessed by FACT-L, anxiety and depression by PHQ-4. Association of pandemic status with time to deterioration (TTD) in QoL scales adjusted for potential covariates was estimated using Cox modelling. PROs were documented for 1166 patients (72%) in the pre-pandemic, 979 (74%) in the pandemic group. Almost 60% of patients were male, median age was 66 years, comorbidities occurred in 85%. Regarding HRQoL, mean-change-from-baseline plots hardly differed between both samples. Approximately 15%-21% of patients reported anxiety, about 19%-27% signs of depression. For the pandemic group, TTD was slightly, but statistically significantly, worse for the physical well-being-FACT-G subscale (HR 1.15 [95%CI 1.02-1.30]) and the anxiety-GAD-2 subscale (HR 1.14 [95%CI 1.01-1.29]). These prospectively collected real-world data provide valuable insights into PROs before and during the COVID-19 pandemic in advanced NSCLC. For the patients, the pandemic seemed to be less of a burden than the disease itself, as there was a considerable proportion of patients with anxiety and depression in both groups.

1065 Background: RIBANNA is a real-world, noninterventional study conducted in Germany evaluating efficacy, safety, and tolerability of RIB in combination with AI/FUL aiming to gain insights into routine clinical practice for pts with HR+, HER2– ABC. Here, we present results of the fourth IA from RIBANNA. Methods: Pre-, peri- and postmenopausal pts who received 1L tx with RIB+AI/FUL, or ET or CT for HR+, HER2– ABC were included in accordance with the German tx guideline. The effect of baseline demographic characteristics, including histological grade, age, previous adjuvant tx, Eastern Cooperative Oncology Group-performance score (ECOG-PS), and metastatic sites on progression-free survival was evaluated using Cox regression model. Results: At data cutoff October 11, 2021, 2598 pts were enrolled in the study (RIB+AI/FUL, n = 2177; ET, n = 239; CT, n = 182). Data from 1L tx were available for 2492 pts (95.9%), second-line tx for 689 pts (26.5%), third-line tx for 263 pts (10.1%), and fourth-line tx for 94 pts (3.6%). Significant differences were observed in baseline mean age and metastatic sites for pts in RIB+AI/FUL cohort vs ET and CT cohorts (both < 0.001). At baseline, the mean (SD) ages of pts were 65.5 (11.6), 70.7 (11.5) and 61.6 (11.6) years in RIB+AI/FUL, ET, and CT cohorts, respectively. While comparing the performance status, 44.2% of pts in RIB+AI/FUL, 34.7% of pts in ET and 42.1% of pts in CT cohort were fully active with ECOG-PS = 0. CNS, liver, or lung metastases were recorded in 42.6% of pts in RIB+AI/FUL, 26.8% of pts in ET and 67.1% of pts in CT cohort. Bone only metastases were reported in 30.8%, 47.9% and 15.0% of pts in RIB+AI/FUL, ET, and CT cohorts, respectively. Overall, 32.1%, 37.7%, and 52.7% of pts discontinued the study in RIB+AI/FUL, ET, and CT cohorts, respectively, the most common reasons being deaths (16.1%,17.2%, and 31.9%, respectively) and lost to follow-up (5.9%, 8.8%, and 9.3%, respectively). The most common tx-emergent adverse event (grade 3 or 4) observed in RIB+AI/FUL cohort was neutropenia (14.8%), while 6.6% and 6.9% of pts in ET and CT cohorts, respectively, experienced neutropenia. The efficacy results from all 3 cohorts, including Kaplan-Meier curves, will be presented during ASCO 2022. Conclusions: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. Overall higher number of pts were treated in 1L with RIB+AI/FUL followed by ET and CT. The differences in baseline characteristics on metastatic pattern, age, and ECOG-PS reflect different selection strategies for 1L tx decision. No new safety signals were identified. Clinical trial information: CLEE011ADE03.

Abstract Background: Ribociclib (RIB; a selective CDK4/6 inhibitor) + endocrine therapy (ET; aromatase inhibitor or fulvestrant along with ovarian suppression in pre- and perimenopausal patients [pts]) received USFDA and EMA approval for pre-, peri- and postmenopausal pts with HR+, HER2- advanced breast cancer (ABC) based on results from phase 3 MONALEESA (ML) trials. In ML-2 trial, first-line treatment (tx) with RIB + letrozole (LET) vs placebo (PBO) + LET significantly improved median progression-free survival (mPFS) in postmenopausal pts with HR+, HER2- ABC. In ML-3 and ML-7 trials, RIB + ET vs PBO + ET showed a significant improvement in mPFS and overall survival among pts with HR+, HER2- ABC, irrespective of menopausal status, line of tx and combination partner. Real-world evidence on the effectiveness, safety, and tolerability of RIB + ET in pts with HR+, HER2- ABC would help to gain insight into routine clinical practice. Methods: RIBANNA is a prospective, noninterventional study ongoing in Germany since October 2017. Pre-, peri- and postmenopausal pts who received first-line tx with RIB + ET, or ET alone or chemotherapy (CT) for HR+, HER2- ABC in accordance with German tx guidelines were included. Data from routine clinical practice in all 3 cohorts, including further lines of sequential therapy, were collected. The third interim analysis data from RIBANNA study was presented in SABCS 2020. Fourth interim analysis data will be presented during SABCS 2021. Results: Till February 11, 2021, 2594 pts were included in the study (RIB + ET, n = 2183; ET, n = 229; CT, n = 182) and the enrollment was stopped; however, pt follow-up will be continued for an additional 4 years. For the fourth interim analysis, full analysis set (comprising all pts, except screening failures and locked pts, who received at least one dose of study medication [safety analysis set] and for whom ≥ 1 post-baseline evaluation was recorded) included 2131 pts (RIB + ET, n = 1814 [81.2%]; ET, n = 175 [73.8%]; CT, n = 142 [72.1%]), while the safety analysis set comprised 2452 pts (RIB + ET, n = 2062 [92.3%]; ET, n = 216 [91.1%]; CT, n = 174 [88.3%]). Until last patient first visit, among 2594 treated pts (including screening failures), data from first-line (1L) tx are available for 2452 pts (94.5%), from second-line (2L) tx for 343 pts (13.2%), and from third-line (3L) tx for 74 pts (2.9%, Table 1). Overall, 23.9%, 27.9%, and 43.4% of pts discontinued the study in RIB + ET, ET, and CT cohorts, respectively. The fourth interim analysis is planned in October 2021, and the final baseline demographic data as well as updated information on safety will be presented during SABCS 2021. Conclusion: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. The data from fourth interim analysis, which is planned in October 2021, including final baseline demographic data and updated safety data will be presented. Table 1. Patient disposition following last patient first visit on February 11, 2021PatientsTotal. (N = 2594). n (%)RIB + AI/FUL (n = 2183). n (%)ET (n = 229). n (%)CT. (n = 182). n (%)Includeda2594 (100.0)2183 (100.0)229 (100.0)182 (100.0)Treated (including screening failures)2452 (94.5)2062 (94.5)216 (94.3)174 (95.6)1L therapyb2452 (94.5)2062 (94.5)216 (94.3)174 (95.6)2L therapyb343 (13.2)264 (12.1)36 (15.7)43 (23.6)3L therapyb74 (2.9)53 (2.4)10 (4.4)11 (6.0)4L therapyb7 (0.3)7 (0.3)0 (0.0)0 (0.0)Discontinued studyc664 (25.6)521 (23.9)64 (27.9)79 (43.4)aAll pts signing informed consent form, bNumber of data set available till February11, 2021, cEnd of documentation with reason other than ‘end of study. Citation Format: Diana Lüftner, Cosima Brucker, Thomas Decker, Peter Fasching, Thomas Göhler, Christian Jackisch, Jan Janssen, Andreas Köhler, Kerstin Lüdtke-Heckenkamp, Marion van Mackelenbergh, Frederik Marmé, Arnd Nusch, Beate Rautenberg, Toralf Reimer, Marcus Schmidt, Rudolf Weide, Pauline Wimberger, Naiba Nabieva, Christian Roos, Achim Wöckel. Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) locally advanced or metastatic breast cancer: Fourth interim analysis from the RIBANNA study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-15.

We investigated the health-related quality of life (HRQoL) of patients with gastrointestinal stromal tumours (GIST). In the multicentre PROSa study, the HRQoL of adult GIST patients was assessed between 2017 and 2019 using the European Organisation for Research and Treatment of Cancer HRQoL questionnaire (EORTC QLQ-C30). We performed group comparisons and multivariate linear regressions. Among 130 patients from 13 centres, the mean global HRQoL was 63.3 out of 100 points. Higher sores indicate better HRQoL. The highest restrictions were in emotional, social, role functioning, insomnia, fatigue, and pain. In multivariate linear regression, we found no significant differences between patients receiving tyrosine kinase inhibitor (TKI) treatment and those without TKI treatment as well as between patients treated with curative or with palliative intent. Patients who received multiple lines of TKI treatment had the most restrictions, notably in physical (unstandardized regression coefficient [B] = -15.7), role (B = -25.7), social (B = -18.4), and cognitive functioning (B = -19.7); fatigue (B = 15.93); general health (B = -14.23); and EORTC-sum score (B = -13.82) compared to all other patients. The highest HRQoL restrictions were in GIST patients receiving multiple lines of TKI therapy. Underlying causes need further investigation.

TPS4163 Background: The multi-targeted tyrosine kinase inhibitor cabozantinib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in adults, who have previously been treated with sorafenib. In the pivotal phase 3 CELESTIAL trial a significant improvement for OS and PFS was shown for cabozantinib in comparison to placebo treated patients (Abou-Alfa GK et al. N Engl J Med 2018; 379:54-63). However, in 62% of patients a dose reduction of cabozantinib was necessary and the median average daily dose was 35.8 mg. The discontinuation rate due to treatment-related adverse events (TRAEs) was 16% and grade 3-4 TRAEs occurred in 68% of patients. For HCC patients treated with sorafenib in first-line, a reduced starting dose of 200 mg BID was not inferior in terms of OS but showed a trend toward a decreased rate of sorafenib discontinuation(Reiss KA et al. J Clin Oncol 2017; 35:3575-3581). The aim of the CaboRISE trial is to study the effect of a reduced starting dose of cabozantinib on tolerability, safety, and efficacy. Methods: The CaboRISE trial is an open-label, single arm, multicenter phase II trial, including patients with advanced stage hepatocellular carcinoma (HCC) with compensated liver cirrhosis (Child-Pugh A) in second line treatment, after first line treatment with sorafenib or lenvatinib. Forty evaluable patients will be enrolled in the study to receive a reduced starting dose of 40 mg cabozantinib once-daily for 4 weeks and subsequent dose escalation to 60 mg cabozantinib once-daily to be maintained until disease progression or intolerable toxicities. The objective of the trial is to assess the tolerability of a reduced starting dose of cabozantinib, in order to reduce the treatment discontinuation rates due to treatment-related adverse events below 10%. Primary endpoint is the treatment discontinuation rate due to TRAEs. Secondary endpoints are overall survival, progression free survival at 10 weeks, objective response rate, time on treatment, treatment exposure, toxicity, and quality of life. Study start of the CaboRISE trial was in October 2020. By February 2021, 7 centers across Germany have been initiated and a total of 4 out of 40 planned patients have been enrolled. The study is currently ongoing. This study is financially supported by Ipsen. ClinicalTrials.gov: NCT04522908 EudraCT: 2020-000775-20. Clinical trial information: NCT04522908.

Abstract Background Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC. Methods In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0-100), which were summarized to the overall VAS score. Results 470 patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (-2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (-7.82 vs. non-responders − 1.97, p = 0.0005). The VAS for pain (-16.37 vs. non-responders − 8.89, p = 0.001) and swallowing of solid food (-16.67 vs. non-responders − 5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05–1.20, p = 0.0009) Conclusion In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.

Abstract Background: The effects of intravenous immunoglobulin G substitution on health status and infections of patients suffering from immunoglobulin G (IgG) deficiencies should be evaluated in a prospective analysis.Methods: Patients with symptomatic primary or secondary IgG deficiencies were interviewed prior to the first IgG infusion (t0) and over the course of their treatment. The respondents rated their current health using a 100-point scale (EQ-5D-5L), ranging from 0 ('worst imaginable health') to 100 ('best imaginable health'). The patients also provided information on the frequency of infections and infections requiring antibiotics in the past 8 weeks. A control group (CG) without oncologic diseases answered the questions on an one-off basis.Results: 106 patients with a median age of 65 years (21-85 years) were investigated. The median serum IgG-concentration changed from 500 mg/dl (t0) to 772 mg/dl (t6). The mean number of infections and of infections requiring antibiotics decreased during IgG substitution significantly. The EQ-5D-5L health status improved from 57 (t0) to 68 (t6), compared to 73 in the CG.Conclusion: During the course of IgG substitution patients reported fewer and less severe infections. Their health status improved but still was inferior to the healthy CG.Previous presentationData were presented in part at the annual meeting of the German, Austrian and Swiss Societies of Hematology and Medical Oncology in Vienna, Austria, 2018.