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Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Purpose: This phase II study evaluated the impact of adding ribociclib to maintenance endocrine therapy (ET) treatment of physicians’ choice following the first palliative chemotherapy in pre- and post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (mBC). Patients and methods: The initial randomized study design was later amended into a single-arm study, and all subsequent patients received ribociclib and ET. The primary end point was locally assessed progression-free survival (PFS). Secondary end points included overall survival (OS), clinical benefit rate (CBR), safety, compliance, and quality of life (QoL). Results: A total of 43 patients received ribociclib + ET and 10 patients received ET only. Median PFS was 12.4 months [95% CI 8.7–24.4] for patients who received ribociclib + ET and 4.75 months [95% CI 1.0–10.3] for those who received ET only. Median OS was not reached for patients who received ribociclib + ET, and 28 (65.1%) patients experienced clinical benefit [95% CI 49.1–79.0]. For patients who received ribociclib + ET, grade 3–4 hematological adverse events (AEs) occurred in 25 (58.1%) patients, and grade 3–4 non-hematological AEs occurred in 17 (39.5%) patients. During the study, 15 patients died – 14 of whom due to tumor-related reasons, and one patient due to pneumonia, which was not treatment-related. Conclusion: The results of the AMICA study show a promising efficacy and safety of maintenance treatment with ribociclib added to ET after at least stable disease following the first metastatic chemotherapy in patients with HR+/HER2-mBC. Trial registration: Anti-hormonal Therapy With Ribociclib in HR-positive/HER2- Negative Metastatic Breast Cancer (AMICA), NCT03555877, https://clinicaltrials.gov/ct2/show/NCT03555877.

Abstract Background The effects of intravenous immunoglobulin G replacement on perceived health and infection susceptibility 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 (t1 - t6). 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 of infections requiring antibiotics in the past 8 weeks. A healthy control group (CG) without oncologic diseases answered the questions once. Results One hundred six 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 replacement significantly. Current health according to EQ-5D-5L improved from 57 (t0) to 68 (t6), compared to 73 in the CG. Conclusion During the course of IgG replacement patients reported fewer and less severe infections. Their health assessment improved but still was inferior to the healthy CG.

Background: In breast cancer and prostate cancer patients, bone metastases (BM) present the main cause of morbidity and often cause debilitating pain, impaired functioning and subsequent deterioration of quality of life (QoL). The management of BM is still challenging. Maintenance or improvement in QoL is the main goal of treatment. Antiresorptive treatment, such as denosumab and bisphosphonates, can help to reduce the frequency of skeletal complications, to control bone pain and potentially to improve QoL. The optimal time point for initiation of antiresorptive therapy is still discussed controversially. In patients with BM, bone pain can be used as a surrogate measure of QoL. However, limited data exist on health-related QoL in patients with BM under antiresorptive treatment. The PROBone registry study evaluated complaints and limitations caused by BM of breast and prostate cancer patients using patient-reported outcomes (PROs) in real-world in Germany. Methods: Between 2014 and 2019, 500 patients with histological confirmation of advanced breast or prostate cancer, diagnosed with BM at start of their first antiresorptive therapy were prospectively enrolled in 65 outpatient-centers specialized in medical oncology across Germany. Changes of QoL were assessed monthly from baseline until a maximum of 12 months using the validated pain score Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) supplemented by questions on general pain and on the impact of time spent for treatment of illness on patients’ daily activities. Statistical analysis was performed descriptively by relative and absolute frequencies. Results: In total, 486 patients were eligible for final analysis, of these 310 were diagnosed with breast cancer and 176 with prostate cancer. Median age was 67 years for breast cancer and 76 years for prostate cancer patients. 79.7% of breast cancer and 59.7% of prostate patients started antiresorptive treatment within 3 months after diagnosis of BM. More than 75% of patients suffered from bone pain at study inclusion. In total 52% of breast cancer patients and 47.9% of prostate cancer patients reported to take pain medication during the observation period. In breast and prostate cancer patients an initial pain reduction after start of BTA was observed: General pain and bone pain levels as well as the median FACT-BP score showed a constant improvement over the first months and maintained stable at a constant level afterwards. Subgroup analysis showed that patients without pain at baseline reported distinctly better FACT-BP scores throughout the whole observation period than patients with pain at baseline. Looking at time-stress (M)-scores, younger breast cancer patients (

Abstract Background Bevacizumab (Avastin®), a recombinant humanized monoclonal antibody, in combination with platinum-doublet chemotherapy has become a routine treatment for advanced non-small-cell lung cancer (NSCLC). The post-authorization, non-interventional study ‘AVAiLABLE’ assessed the effectiveness and safety of bevacizumab combined with chemotherapy as first-line treatment. Methods Nine hundred and eighty-seven adult patients (mean age 61.5 years, 59.8% male) with non-resectable advanced, metastatic or recurrent, predominantly non-squamous NSCLC were evaluated at 185 sites across Germany. 72.8% of the patients had stage IV disease at start of observation, 90.1% had histologically confirmed adenocarcinoma and 80.8% met the bevacizumab label ‘NSCLC other than predominantly squamous cell histology’. According to bevacizumab label, chemotherapy plus bevacizumab was recommended, followed by bevacizumab maintenance therapy. Effectiveness endpoints included response rates and progression-free survival (PFS); safety endpoints comprised adverse drug reactions (ADRs). Patients were followed until progression or intolerable toxicity. Data were evaluated by descriptive statistical methods. Results Median PFS was 7.4 months (95% CI: 7.1; 8.4), overall response rate (ORR) 45.6% and disease control rate (DCR) 75%. The majority of patients (72.7%) achieved partial response or stable disease. Complete response was reached by 2.3%. 33.6% of patients experienced an ADR of grade ≥ 3. Bevacizumab-related ADRs of grade ≥ 3 occurred in 5.7% of patients, with the highest incidence for leukopenia, neutropenia, and hypertension. Conclusions Results of the non-interventional study ‘AVAiLABLE’ confirmed the effectiveness and safety of bevacizumab in combination with platinum-based chemotherapy as first-line treatment for advanced NSCLC in accordance with previous studies. No new safety signals were identified. Maintenance therapy with bevacizumab was well tolerated and safe even over extended periods (> 20 cycles). Trial registration ClinicalTrials.gov Identifier: NCT02596958; registered on 4 November 2015.

Background: Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC)., Objective: To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies., Design, Setting and Participants: Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany., Interventions: Cabozantinib was administered as a standard of care., Outcome Measurements and Statistical Analysis: Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized., Results and Limitations: About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study., Conclusions: Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment., Competing Interests: Disclosure VG: Compensated lectures: AstraZeneca, Astellas, BMS, EISAI, Ipsen, Janssen-Cilag, Merck, MSD, Pfizer, ONO Pharmaceutical, Novartis/AAA. Advisory Board: Apogepha, BMS; EISAI, EUSA Pharm, Cureteq, Debiopharm, Gilead, Janssen-Cilag, Merck, MSD, Pfizer, Novartis, Oncorena, PCI Biotech. Research Grant: AstraZeneca, BMS, MSD, Ipsen, Pfizer. Travel support: AstraZeneca, Ipsen, Merck, Janssen, Pfizer MB: RR: Advisory Board: Apogepha,Ipsen, Merck .Pfizer Travel support: Janssen, Pfizer GN: compensated lectures: Roche Pharma, MEDAC, Pfizer, BMS, AstraZeneca, Merck, Janssen-Cilag, Astellas; Advisory Boards: Roche Pharma, Sanofi, BMS, Merck Serono, Pfizer, MEDAC, Ipsen, Janssen, Travel support:Roche Pharma, Pfizer, Merck, Janssen, maunscript writing: Pfizer, BMS, Merck MJS: Compensated lectures: Astellas, Apogepha, Bayer, BMS, EISAI, Hexal, Ipsen, Merck, Pfizer, Medac, MSD, Janssen-Cilag. Advisory board: BMS, Gilead, Ipsen, Merck, Novartis, Pfizer, MSD, Janssen-Cilag. Congress: Apogepha, Janssen-Cilag, Ipsen, Pfizer. Research Grants: Gilead, Ipsen, Janssen-Cilag, AstraZeneca, QED, MSD. FA: none, MM: none, MC: none, MOZ: none AW: Compensated lectures: AIO, BMS, Gilead, Janssen, Lilly, iOMEDICO Advisory Board: BMS;Gilead, Lilly Merck, MSD, Pfizer,Janssen Research Grant: AIO, iOMEDICO AH: none JC: none CD: Compensated lectures from Janssen-Cilag, Ipsen. Advisory Board: Janssen-Cilag, Ipsen. Travel support: Janssen-Cilag, Ipsen and Bayer HT: none, MS: none, DS: none PI: Compensated lectures: AstraZeneca, BMS, EISAI, Merck, MSD, Pfizer, Novartis/AAA. Advisory Board: Apogepha, BMS; EISAI, EUSA Pharm, Gilead, Ipsen, Merck, MSD, Pfizer, Novartis, Oncorena, PCI Biotech. Research Grant: AstraZeneca, BMS, MSD, Ipsen, Pfizer. Travel support: AstraZeneca, Ipsen, Merck, Pfizer, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)