Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.

PURPOSE: Non-inflamed (cold) tumors such as leiomyosarcoma do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis or PARP inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pretreated patients with leiomyosarcoma. PATIENTS AND METHODS: Patients were randomized to receive durvalumab 1,500 mg IV every 4 weeks with either olaparib 300 mg twice a day orally (Arm A) or cediranib 20 mg every day orally 5 days/week (Arm B) until unacceptable toxicity or disease progression. Paired tumor biopsies, serial radiologic assessments and stool collections were performed. Primary endpoints were safety and immune cell changes in the TME. Objective responses and survival were correlated with transcriptomic, radiomic, and microbiome parameters. RESULTS: Among 30 heavily pretreated patients (15 on each arm), grade ≥ 3 toxicity occurred in 3 (20%) and 2 (13%) on Arms A and B, respectively. On Arm A, 1 patient achieved partial response (PR) with increase in CD8 T cells and macrophages in the TME during treatment, while 4 had stable disease (SD) ≥ 6 months. No patients on Arm B achieved PR or SD ≥ 6 months. Transcriptome analysis showed that baseline M1-macrophage and B-cell activity were associated with overall survival. CONCLUSIONS: Durvalumab plus olaparib increased immune cell infiltration of TME with clinical benefit in some patients with leiomyosarcoma. Baseline M1-macrophage and B-cell activity may identify patients with leiomyosarcoma with favorable outcomes on immunotherapy and should be further evaluated.

Comparative review of pharmacological therapies in individuals with HER2-positive advanced breast cancer with focus on hormone receptor subgroups.

Breast cancer is the fifth leading cause of cancer-related deaths worldwide. The randomized controlled trials (RCTs) of targeted therapies in human epidermal receptor 2 (HER2)-positive advanced breast cancer (ABC) have provided an evidence base for regulatory and reimbursement agencies to appraise the use of cancer therapies in clinical practice. However, a subset of these patients harbor additional biomarkers, for example, a positive hormone receptor status that may be more amenable to therapy and improve overall survival (OS). This review seeks to explore the reporting of evidence for treatment effects by the hormone receptor status using the RCT evidence of targeted therapies for HER2-positive ABC patients. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to identify published RCTs. Extracted data were synthesized using network meta-analysis to obtain the relative effects of HER2-positive-targeted therapies. We identified a gap in the reporting of the effectiveness of therapies by the hormone receptor status as only 15 out of 42 identified RCTs reported hormone receptor subgroup analyses; the majority of which reported progression-free survival but not OS or the overall response rate. In conclusion, we recommend that future trials in ABC should report the effect of cancer therapies in hormone receptor subgroups for all outcomes.

Cancer pain control in a Nigerian oncology clinic: treating the disease and not the patient.

INTRODUCTION: inadequate pain control negatively impacts the quality of life of patients with cancer while potentially affecting the outcome. Proper pain evaluation and management are therefore considered an important treatment goal. This study assessed the prevalence of pain, the prescribing patterns, and the efficacy of pain control measures in cancer patients at the Radiation Oncology Unit of the Lagos University Teaching Hospital, Lagos. METHODS: this was a longitudinal study design recruiting adults attending outpatient clinics. Participants were assessed at initial contact and again following six weeks using the Universal Pain Assessment Tool developed by the UCLA Department of Anaesthesiology. RESULTS: among the patients reviewed, 34.0% (118 of 347) were at the clinic, referred for initial assessment following primary diagnosis. All respondents had solid tumours; the most common was breast cancer. The prevalence of pain at initial assessment was 85.9% (298 of 347), with over half of respondents, 74.5% (222 of 347) characterising their pain as moderate to severe. Over a quarter, 28.9% (100 of 347) of patients were not asked about their pain by attending physicians, and none of the patients had a pain assessment tool used during evaluation. In 14.4% (43 of 298) of patients, no intervention was received despite the presence of pain. At six weeks review, 31.5% (94 of 298) of patients had obtained no pain relief despite instituted measures. CONCLUSION: under-treatment of cancer pain remains a significant weak link in cancer care in (Low-to-middle-income country) LMICs like Nigeria, with a significant contributor being physician under-evaluation and under-treatment of pain. To ensure pain eradication, the treatment process must begin with a thorough evaluation of the patient's pain, an explicit pain control goal and regular reevaluation.

Comparing attitudes of younger and older patients towards cancer clinical trials.

OBJECTIVES: To determine the attitudes of patients towards cancer clinical trials (CCTs) and assess the differences between older and younger patients. MATERIALS AND METHODS: Patients with cancer, receiving treatment or in follow-up in University Hospital Waterford, Ireland were eligible. Patients completed a self-administered questionnaire. To determine attitudes towards CCTs, patients indicated their preference if offered participation in three hypothetical studies (cancer prevention/screening trial; CCT comparing standard to new treatment; a trial of new drug where no standard exists). Patients' reasons to or not to participate in CCTs were explored. RESULTS: From May 2014 to March 2015, 219 patients were accrued, 119 <65years and 100 ≥65years. Twenty-two (18%) younger and 4 (4%) older patients had been/were actively enrolled on a CCT (p=0.0012). No older patient and 5 (4%) of younger patients had enquired about CCT availability. For the CCT questions, 85 (71%) younger vs 57 (57%) older patients would participate in a prevention/screening CCT (p=0.033); 60 (50%) vs 44 (44%) for standard vs new drug (p=0.415), and 83 (69%) vs 78 (78%) for a CCT where no standard exists (p=0.218). The most common reason to participate in a CCT was a recommendation from the oncologist -98% <65years vs 87% ≥65years (p=0.001), with health problems being the leading reason not to participate, 86% vs 72% (p=0.01), respectively. CONCLUSIONS: Older and younger patients in this study gave similar importance to reasons for and against participation in CCTs. Most patients did not actively seek out a CCT, which may reflect a lack of awareness and a need for better education.