Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme.

BACKGROUND AND AIMS: Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. METHODS: Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). RESULTS: Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. CONCLUSION: This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists.

BACKGROUND: Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians' views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation. METHODS: A study-specific 17-question survey was emailed (01 February-12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics. RESULTS: Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation. CONCLUSION: PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians' hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation.

Patterns of care for people with small cell lung cancer in Victoria, 2011-19: a retrospective, population-based registry data study.

OBJECTIVES: To report stage-specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC). DESIGN: Cross-sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR). SETTING, PARTICIPANTS: All people diagnosed with SCLC in Victoria during 1 April 2011 - 18 December 2019. MAIN OUTCOME MEASURES: Stage-specific management and treatment of people with SCLC; median survival time. RESULTS: During 2011-19, 1006 people were diagnosed with SCLC (10.5% of all lung cancer diagnoses in Victoria); their median age was 69 years (interquartile range [IQR], 62-77 years), 429 were women (43%), and 921 were current or former smokers (92%). Clinical stage was defined for 896 people (89%; TNM stages I-III, 268 [30%]; TNM stage IV, 628 [70%]) and ECOG performance status at diagnosis for 663 (66%; 0 or 1, 489 [49%]; 2-4, 174 [17%]). The cases of 552 patients had been discussed at multidisciplinary meetings (55%), 377 people had received supportive care screening (37%), and 388 had been referred for palliative care (39%). Active treatment was received by 891 people (89%): chemotherapy, 843 (84%); radiotherapy, 460 (46%); chemotherapy and radiotherapy, 419 (42%); surgery, 23 (2%). Treatment had commenced within fourteen days of diagnosis for 632 of 875 patients (72%). Overall median survival time from diagnosis was 8.9 months (IQR, 4.2-16 months; stage I-III: 16.3 [IQR, 9.3-30] months; stage IV: 7.2 [IQR, 3.3-12] months). Multidisciplinary meeting presentation (hazard ratio [HR], 0.66; 95% CI, 0.58-0.77), multimodality treatment (HR, 0.42; 95% CI, 0.36-0.49), and chemotherapy within fourteen days of diagnosis (HR, 0.68; 95% CI, 0.48-0.94) were each associated with lower mortality during follow-up. CONCLUSION: Rates of supportive care screening, multidisciplinary meeting evaluation, and palliative care referral for people with SCLC could be improved. A national registry of SCLC-specific management and outcomes data could improve the quality and safety of care.

"Take the tablet or don't take the tablet?"-A qualitative study of patients' experiences of self-administering anti-cancer medications related to adherence and managing side effects.

PURPOSE: Medication non-adherence is a well-recognised problem in cancer care, negatively impacting health outcomes and healthcare resources. Patient-related factors influencing medication adherence (MA) are complicated and interrelated. There is a need for qualitative research to better understand their underlying interaction processes and patients' needs to facilitate the development of effective patient-tailored complex interventions. This study aimed to explore experiences, perceptions, and needs relating to MA and side effect management of patients who are self-administering anti-cancer treatment. METHODS: Semi-structured audio-recorded interviews with patients who have haematological cancer were conducted. A comparative, iterative, and predominantly inductive thematic analysis approach was employed. RESULTS: Twenty-five patients from a specialist cancer hospital were interviewed. While self-administering cancer medications at home, patients' motivation to adhere was affected by cancer-related physical reactions, fears, cancer literacy and beliefs, and healthcare professional (HCP) and informal support. Patients desired need for regular follow-ups from respectful, encouraging, informative, responsive, and consistent HCPs as part of routine care. Motivated patients can develop high adherence and side effect self-management over time, especially when being supported by HCPs and informal networks. CONCLUSION: Patients with cancer need varied support to medically adhere to and manage side effects at home. HCPs should adapt their practices to meet the patients' expectations to further support them during treatment. We propose a multi-dimensional and technology- and theory-based intervention, which incorporates regular HCP consultations providing tailored education and support to facilitate and maintain patient MA and side effect self-management.

Telehealth in oncology: a cost analysis to evaluate the financial impact of implementing regional trial hubs within a phase 3 cancer clinical trial.

This cost analysis, from a societal perspective, compared the cost difference of a networked teletrial model (NTTM) with four regional hubs versus conventional trial operation at a single metropolitan specialist centre. The Australian phase 3 cancer interventional randomised controlled trial included 152 of 328 regional participants (patient enrolment 2018-2021; 6-month primary end point). The NTTM significantly reduced (AU$2155 per patient) patient travel cost and time and lost productivity.

Infective complications in cancer patients treated with subcutaneous versus intravenous trastuzumab and rituximab: An individual patient data meta-analysis.

BACKGROUND: Investigation of infection risk with subcutaneous versus intravenous trastuzumab and rituximab administration in an individual patient data (IPD) and published data meta-analysis of randomised controlled trials (RCTs). METHODS: Databases were searched to September 2021. Primary outcomes were serious and high-grade infection. Relative-risk (RR) and 95% confidence intervals (95%CI) were calculated using random-effects models. RESULTS: IPD meta-analysis (6 RCTs, 2971 participants, 2320 infections) demonstrated higher infection incidence with subcutaneous versus intravenous administration, without reaching statistical significance (serious: 12.2% versus 9.3%, RR 1.28, 95%CI 0.93to1.77, P = 0.13; high-grade: 12.2% versus 9.9%, RR 1.32, 95%CI 0.98to1.77, P = 0.07). With exclusion of an outlying study in post-hoc analysis, increased risks were statistically significant (serious: 13.1% versus 8.4%, RR 1.53, 95%CI 1.14to2.06, P = 0.01; high-grade: 13.2% versus 9.3%, RR 1.56, 95%CI 1.16to2.11, P < 0.01). Published data meta-analysis (8 RCTs, 3745 participants, 648 infections) demonstrated higher incidence of serious (HR 1.31, 95%CI 1.02to1.68, P = 0.04) and high-grade (HR 1.52, 95%CI 1.17to1.98, P < 0.01) infection with subcutaneous versus intravenous administration. CONCLUSIONS: Results suggest increased infection risk with subcutaneous versus intravenous administration, although IPD findings are sensitive to exclusion of one trial with inconsistent results and identified risk-of-bias. Ongoing trials may confirm findings. Clinical surveillance should be considered when switching to subcutaneous administration. PROSPERO registration CRD42020221866/CRD42020125376.

Mechanisms of Cognitive Behavioral Therapy and Light Therapy for Cancer-Related Insomnia: A Randomized Clinical Trial during Chemotherapy for Breast Cancer.

STUDY OBJECTIVES: This study aimed to investigate the mechanisms of a combined brief cognitive behavioral plus bright light therapy (CBT-I+Light) in women receiving chemotherapy. METHODS: Women (N = 101) were randomly assigned to CBT-I+Light or treatment as usual plus relaxation audios (TAU+). Participants completed sleep diaries and wore an actigraph during the 6-week intervention period. Patient-reported outcomes were assessed at baseline, mid-point (week 3), and later (week 6). Cognitive (i.e., dysfunctional sleep beliefs, pre-sleep cognitions, and arousal) and behavioral (i.e., time in bed awake and day-to-day out-of-bedtime variability) mechanisms were examined. RESULTS: Cognitively, both groups declined significantly in overall dysfunctional sleep beliefs from pre- to post-intervention (both p< .04); however, they did not differ on sleep-related beliefs nor pre-sleep cognitions and arousal at post-intervention (both p> .50). Dysfunctional beliefs sleep expectations subscale was lower in CBT-I+Light versus TAU+ (p= .01). Behaviorally, CBT-I+Light reported less overall time in bed awake after the start of the intervention (p< .05) and significantly less time in bed during the morning until the final week of the intervention period. Out-of-bedtime day-to-day variability was lower in the CBT-+Light vs TAU+ at the final intervention day. CONCLUSION: Mechanisms of CBT-I+Light during chemotherapy remain to be shown. Our results suggest that changes in behavioral mechanisms may be associated with sleep improvements within this cohort. Future studies should assess the role of additional mechanisms (e.g., sleep effort) within larger samples. Whilst intervention brevity is important, more potent interventions may be required to achieve robust changes in target mechanisms.

A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing.

BACKGROUND: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type). METHODS: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life). RESULTS: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27-0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24-0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93-1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66-2.44], p = 0.47). CONCLUSION: PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response. REGISTRATION NUMBER: The study is registered with PROSPERO, registration number CRD42020223768.

A randomised controlled trial of clinical pharmacy intervention versus standard care to improve medication adherence in outpatients with head and neck cancer receiving radiotherapy.

PURPOSE: Patient understanding of medicines information and adherence to medication instructions are important variables for ensuring optimal cancer care. This randomised controlled trial (RCT) aimed to evaluate the impact of an outpatient clinical pharmacy service on medication adherence and symptom burden in cancer patients. METHODS: In this single-centre RCT, 115 patients were randomised 1:1 to a pharmacist-led pharmaceutical care program (intervention, n = 59) versus standard of care (control, n = 56) within an outpatient multidisciplinary radiotherapy clinic. The primary endpoint was medication adherence as assessed by Medication Understanding and Use Self-Efficacy (MUSE) scale and Teach-Back assessment. Secondary endpoints were patient-reported symptom burden assessed by the Edmonton Symptom Assessment Scale (ESAS). Patients were assessed at baseline (weeks 1-2) and at discharge from radiotherapy (weeks 5-7). RESULTS: Polypharmacy (use of five or more medications) was observed in 26% of patients at baseline compared to 97% at discharge. Patient self-efficacy and medication adherence was higher in the intervention arm compared to the control arm, with a mean MUSE score difference of 2.70 (95% CI 1.24, 4.17) after adjustment for baseline, and a higher proportion of patients with average Teach-Back score of four or more (86% vs 14%; odds ratio (OR) 46.09, 95% CI 14.49, 146.56). The mean (SD) scores for aggregate ESAS (0-100) at discharge were 26.2 (14.0) in the intervention arm and 32.0 (15.8) in the control arm demonstrating lower overall symptom burden associated with the intervention (mean score difference adjusted for baseline - 0.52; 95% CI - 1.03, - 0.01). CONCLUSION: A structured outpatient clinic pharmacy service significantly improved medication adherence and reduced overall symptom burden in patients receiving radiotherapy.

Impact of coronavirus of 2019 on the delivery of pharmacy services to patients with cancer: An international survey of oncology pharmacy practitioners.

INTRODUCTION: The coronavirus of 2019 pandemic has necessitated vast and rapid changes in the way oncology pharmacy services are delivered around the world. METHODS/AIMS: An international survey of oncology pharmacists and technicians was conducted via the International Society of Oncology Pharmacy Practitioners and collaborating global pharmacy organisations to determine the impact that the coronavirus of 2019 has had on pharmacy service delivery, pharmacy practitioners and oncology practice. RESULTS: The survey received 862 responses from 40 different countries from September to October 2020. The majority of respondents were pharmacists (n = 841, 97.6%), with 24% involved in the direct care of patients with the coronavirus of 2019. Of the survey participants, 55% increased their time working remotely, with remote activities including dispensing, patient assessment/follow-up and attending multi-disciplinary rounds. Respondents reported a 72% increase in the use of technology to perform remote patient interaction activities and that participation in educational meetings and quality improvement projects was reduced by 68% and 44%, respectively. Workforce impacts included altered working hours (50%), cancelled leave (48%) and forced leave/furloughing (30%). During the pandemic, respondents reported reduced access to intensive care (19%) and anti-cancer (15%) medications. In addition, 39% of respondents reported reduced access to personal protective equipment, including N95 masks for chemotherapy compounding. Almost half of respondents (49%) reported that cancer treatments were delayed or intervals were altered for patients being treated with curative intent. A third of practitioners (30%) believed that patient outcomes would be adversely impacted by changes to pharmacy services. Sixty-five percent of respondents reported impacts on their mental health, with 12% utilising support services. CONCLUSION: The coronavirus of 2019 pandemic has altered the way oncology pharmacy services are delivered. These results demonstrate the adaptability of the oncology pharmacy profession and highlight the importance of formal evaluation of the varied practice models to determine the evidence-based practices that enhance pharmacy services and, thus, should be reinstated as soon as practical and reasonable.

Intrathecal Morphine in Postoperative Analgesia for Colorectal Cancer Surgery: A Retrospective Study.

BACKGROUND: Colorectal cancer surgery is commonly performed with adequate analgesia essential for patient recovery. This study assessed the effectiveness of intrathecal morphine and patient-controlled analgesia (ITM + PCA) vs patient-controlled analgesia alone (PCA) for postoperative pain management in colorectal cancer surgery. METHODS: This retrospective study extracted and analyzed data covering a 4-year period (2014-2018) from a clinical database with 24- and 48-hour postsurgery follow-up. Primary outcomes included pain scores, median opioid consumption (oral morphine equivalence dose), sedation, nausea and vomiting, and length of admission. Outcomes were analyzed for ITM + PCA vs PCA alone, overall and stratified by laparotomy or laparoscopy procedures. RESULTS: In total, 283 patients were included: ITM + PCA (163) and PCA alone (120). Median opioid consumption in the first 24 hours for ITM + PCA vs PCA alone was lower for laparotomy (-32.7 mg, P<0.001) and laparoscopy (-14.3 mg, P<0.001). Median pain score (worst pain) within the first 24 hours for ITM + PCA vs PCA alone was similar for laparotomy (P>0.05) and lower for laparoscopy (-1 unit, P=0.031). Sedation occurred less frequently for ITM + PCA vs PCA at 24 hours (3.5% vs 11.4%, P=0.031), with nonsignificant reduction at 48 hours (4.8% vs 18.8%, P=0.090) for laparotomy, but with no difference for laparoscopy (P>0.05). Incidence of nausea and vomiting and length of admission were similar for ITM + PCA vs PCA alone for laparotomy or laparoscopy (P>0.05). CONCLUSION: This retrospective study demonstrated that ITM + PCA can achieve similar analgesic effects after laparotomy and laparoscopy colorectal cancer surgery compared with PCA alone while resulting in a reduction of oral opioid consumption and lower incidence of sedation.

Educational needs of oncology pharmacists: A survey by the International Society of Oncology Pharmacy Practitioners.

BACKGROUND: The International Society of Oncology Pharmacy Practitioners (ISOPP) is committed to providing educational resources to members for their continuous learning and professional development. This survey was conducted to explore the educational needs of International Society of Oncology Pharmacy Practitioners members for the purpose of developing resources to support future learning relevant to the diverse global pharmacy practitioner membership of our society. METHODS: A cross-sectional survey of International Society of Oncology Pharmacy Practitioners membership was conducted between 10 December 2018 and 15 January 2019. The survey contained 17 questions and consisted of four sections: (1) respondents' demographics, (2) common challenges/barriers faced by members in accessing oncology pharmacy education, (3) areas within oncology pharmacy where members need education and (4) preferred methods of education delivery. Descriptive statistics were utilized to summarize survey results. RESULTS: The survey was completed by 62 out of 363 International Society of Oncology Pharmacy Practitioners members (17% response rate). Respondents were from 19 different countries, representing all the habitable continents. Most respondents were practicing in North America (21%), Oceania (21%) and Asia (16%). The majority of respondents worked in inpatient cancer units (60%), ambulatory tertiary cancer centres (31%) and academia (26%). Reported barriers to accessing education relevant to oncology pharmacy practice included lack of financial support (44%), time spent travelling to attend educational activities (39%), limited learning opportunities in their country of practice (34%) and limited growth of the oncology pharmacy discipline in their country of practice (32%). The content areas of greatest demand included pharmacotherapy of various cancers followed by oncology pharmacy research, International Society of Oncology Pharmacy Practitioners oncology pharmacy practice standards, supportive care and medication safety. Among educational activities offered by International Society of Oncology Pharmacy Practitioners, respondents valued annual International Society of Oncology Pharmacy Practitioners symposia and Journal of Oncology Pharmacy Practice the most. Most respondents (87%) indicated webinars as an effective educational tool. CONCLUSION: Among an international oncology pharmacist cohort, we identified practice areas prioritized by pharmacists for continuing and professional development. Time and cost were common barriers to education, both in developing and developed countries. These survey findings may help to guide future education initiatives of International Society of Oncology Pharmacy Practitioners and other providers of pharmacist oncology education.

Value of Precision Medicine in Advanced Non-Small Cell Lung Cancer: Real-World Outcomes Associated with the Use of Companion Diagnostics.

BACKGROUND: Companion diagnostic (CDx) testing for patients with advanced non-small cell lung cancer (aNSCLC) identifies patients more likely to benefit from biomarker-driven treatments. METHODS: Patients with nonsquamous cell (non-Sq) aNSCLC from the Flatiron Health database (diagnosed January 1, 2011-May 31, 2018) who had CDx testing were compared with those who had no reported evidence of testing. The association between CDx testing and overall survival was evaluated by unadjusted and adjusted Cox proportional hazards regression models. Logistic regression analysis identified characteristics associated with CDx testing. The revised modified Lung Cancer Prognostic Index and other factors identified a priori were included in the adjusted models. RESULTS: A total of 17,555 patients with non-Sq aNSCLC (CDx, n = 14,732; no CDx, n = 2,823) with mean ± SD age of 67.2 ± 10.0 years were included. Most were insured (91.7%) and white (67.1%). Asian patients and those who were never-smokers were more likely to undergo CDx testing. Those with CDx testing lived longer than those without (median [95% confidence interval (CI)] survival, 13.04 [12.62-13.40] vs. 6.01 [5.72-6.24] months) and had a decreased mortality risk (adjusted hazard ratio [95% CI], 0.72 [0.69-0.76]). A survival advantage was also seen for patients with CDx testing who received biomarker-driven first-line therapy. CONCLUSION: Patients with non-Sq aNSCLC who had CDx testing had a greater survival benefit than those without, supporting broader use of CDx testing in routine clinical practice to identify patients more likely to benefit from precision medicine. IMPLICATIONS FOR PRACTICE: Companion diagnostic (CDx) testing coupled with biomarker-driven treatment offers a greater survival benefit for patients with advanced non-small cell lung cancer (aNSCLC). In this study, patients with nonsquamous aNSCLC from Flatiron Health, a large, real-world oncology database, with CDx testing had a reduced mortality risk and lived longer than patients without reported evidence of CDx testing; those who received biomarker-driven therapy as their first line of treatment were likely to survive three times longer than those who did not. These results demonstrate the clinical utility of CDx testing as the first step in treating nonsquamous aNSCLC in real-world clinical practice.

Pulmonary function testing for the early detection of drug-induced lung disease: a systematic review in adults treated with drugs associated with pulmonary toxicity.

Pulmonary function tests (PFT) are sometimes monitored during treatment with known pulmonary toxic drugs to detect asymptomatic drug-induced interstitial lung disease (DILD). We conducted a systematic review to assess the accuracy of PFT, including the diffusing capacity for carbon monoxide (DLCO), for early detection of DILD in a range of drugs. Using a pre-specified, registered review protocol, OvidMEDLINE and EMBASE were searched from 1946 to February 2018. Two reviewers independently screened abstracts and reviewed full-text articles for inclusion. Included studies were assessed for risk of bias using adapted QUADAS-2 domains and primary outcome data were extracted and entered into RevMan5 to estimate sensitivity and specificity with 95% confidence intervals (CI). The search identified 4065 citations and included 42 studies. The most commonly studied drugs were bleomycin and amiodarone. Due to clinical heterogeneity between studies, a pooled analysis was not performed. Sensitivity of monitoring with DLCO varied between 0 and 100%, with the majority of studies finding a sensitivity of <80%. CI were wide for the majority of studies. Specificity was less than 90% in all studies. Risk of bias was high for the majority of studies for the quality domain of reference standard. The findings of this review do not support routine PFT for early detection of DILD. Due to methodological limitations, the relatively small number of participants and the low prevalence of DILD in the included studies, there remains significant uncertainty about the sensitivity of PFT to screen for DILD.

Global oncology pharmacy response to COVID-19 pandemic: Medication access and safety.

Response, action, and adaptation of the way health services are delivered will impact our ability to provide optimized and continuity of care while acting within resource constraints imposed by COVID-19. Care for patients with cancer is particularly important given increased infection rates and worse outcomes from COVID-19 in this patient population, as well as potential adverse outcomes if treatment pathways need to be compromised. In this commentary, we provide a global oncology pharmacy perspective (including both developed and developing nations) on how COVID-19 has impacted access to and delivery of cancer therapies. This perspective was prepared by the International Society of Oncology Pharmacy Practitioners, with input from national and regional oncology pharmacy practice groups (42 practice leaders from 28 countries and regions) who contributed to a snapshot survey between 10 and 22 April 2020. Specifically, we highlight challenges related to safe handling of hazardous drugs and maintaining high-quality medication safety standards that have impacted various stakeholders.

Parecoxib as an adjunct therapy for the treatment of refractory non-surgical cancer pain.

BACKGROUND: Evidence for the use of short-term daily parenteral parecoxib for refractory or uncontrolled non-surgical cancer pain is limited. This study aimed to characterise the real-world off-label use and report on clinical experiences in an Australian cancer cohort. METHODS: Eligible patients received at least one dose of parecoxib of an intended three-day course between October 2015 and December 2018. Data were collected to characterise the parecoxib treatment cohort (cancer diagnosis, metastases, sites and types of pain and prior analgesia). Parecoxib-related adverse events, pain scores (worst and median), and concurrent opioid use were assessed at 24 h pre (T0) and 24 (T1), 48 (T2), 72 (T3) and 96 h (T4) post first parecoxib dose. RESULTS: Sixty-five patients (39 males and 26 females) and 68 courses of parecoxib (three patients treated twice) were included in analyses: metastatic disease (86%), bone pain (54%) and taking ≥3 classes of analgesic medications (69%). Pain types varied (46% non-specific, 22% neuropathic and 32% other). Most (94%) received parecoxib by subcutaneous administration. Following parecoxib, median 24-h pain scores and worst pain scores improved for 59% (40/68) and 50% (34/68) of patients, respectively. In the first 24 h (T0 to T1), median (4 vs. 2, p < 0.01) and worst (6 vs. 5, p < 0.01) pain scores were reduced and sustained to T4 (4 vs. 2.5, p = 0.01). Breakthrough analgesia requirements reduced for 63% (43/68) of patients, while total concurrent opioid use remained constant. Mean/median oral morphine equivalence for T0 vs. T1 was 111 mg/75 mg vs. 162 mg/90 mg, (p > 0.8). Two patients ceased parecoxib due to renal/liver function abnormalities and two experienced mild injection-site reactions. CONCLUSIONS: In this real-world study, parecoxib was utilised as adjunctive therapy in a select patient cohort to contribute to reduced pain scores with no new safety signals. Prospective randomised studies in larger cohorts would improve understanding of the effects of parecoxib.

Radiation oncology outpatient medication management needs and service gaps - A cross-sectional study of patients and clinicians.

BACKGROUND: Patients receiving radiotherapy for the treatment of cancer can have complex medication requirements related to the management of side-effects and impaired swallowing ability. This study surveyed patients and clinicians to identify service gaps and unmet medication management needs. METHODS: Patient and clinician surveys were developed by a multidisciplinary team based on previously validated questionnaires. The patient survey focused on medication use and adherence. The clinician survey was based around a clinical case study and focused on identifying service gaps and practice variations. This survey was disseminated to radiation oncologists, pharmacists and nurses involved with the care of head and neck or lung cancer patients in Victoria. RESULTS: A total of 93 surveys were completed including 53 patient surveys and 40 clinician surveys. Radiotherapy patients reported high medication usage with up to 53% taking five or more medications daily. When asked the same set of questions relating to medication education requirements, patients receiving polypharmacy reported greater needs (72%) than recognised by the surveyed multidisciplinary clinician group (58%). They also reported a non-adherence rate of 46%. In addition, further disparities were identified in clinician practices and their approach to clinical situations which may result in conflicting advice and confusion for patients. CONCLUSION: While recognising deficiencies relating to the provision of medication information, oncologists, nurses and pharmacists underestimated patient needs for medication information, education and follow-up. Findings support the rationale for integration of pharmacy services within the radiotherapy clinics to support patient care and bridge service gaps relating to medication management.

Paroxetine for the treatment of intractable and persistent cough in patients diagnosed with cancer.

INTRODUCTION: Intractable and persistent cough is experienced by more than a third of patients with advanced cancer, with a significant negative impact on quality of life. Pharmacological treatment has been of little help in some patients. Limited evidence suggests novel agents such as paroxetine may reduce cough severity. This retrospective study aimed to assess effectiveness and tolerability of paroxetine for the treatment of intractable cough in patients with cancer. METHODS: Single-centre medical record review of paroxetine use in patients with advanced malignancy and cough treated at an Australia tertiary referral cancer centre between 1 October 2012 and 1 October 2017. Data relating to cough type and severity, response and adverse events were extracted from medical records. Cough type was described as non-productive dry cough, productive chesty cough or cough exhibiting both non-productive and productive features (mixed cough). RESULTS: Overall, 24/34 patients (71%) experienced a major or moderate reduction in their cough severity after treatment with paroxetine. Nearly half (47%) described a major improvement and a quarter (24%) moderate improvement. Of the 34 patients, nearly half had a lung primary cancer (16/34, 47%) and nearly all (17/18) of those without lung cancer had lung metastases from another primary cancer. Patients with dry cough reported greater benefit from paroxetine. Of the 56% (19/34) of patients with non-productive dry cough, 80% (15/19) reported an improvement in symptoms post paroxetine. The remaining 15 patients, 44% of the group, presented with either a productive chesty cough (9/34, 27%) or mixed cough (6/34, 18%). Of these patients, 60% (9/15) reported an improvement in symptoms. Two thirds of patients were commenced on paroxetine 10 mg (22/34, 65%), with the remainder starting at 20 mg (14/34, 35%). CONCLUSION: Paroxetine may be an effective, novel, off-label treatment for intractable and persistent cough in patients with advanced cancer.

A systematic review of the impact of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies.

BACKGROUND: Patients receiving anticancer therapies are frequently prescribed complex and high-risk medication regimens, which at times can result in medication misadventures. The objective of this review was to assess the effect of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies, including patients undergoing radiotherapy. METHODS: A systematic review of original publications indexed in EMBASE, MEDLINE and Cochrane Library from June 2007 to June 2017. Eligible studies evaluated outpatient pharmacy clinic services for cancer patients and reported at least one medication-related quantitative outcome measure. Two authors independently reviewed full-text articles for inclusion, then extracted data and performed quality and risk of bias assessments. RESULTS: Of 908 identified publications, 13 met predefined eligibility criteria; 1 randomised control trial, 2 controlled cohort studies and 10 uncontrolled before-after studies. Many excluded studies described outpatient pharmacy services but lacked medication-related outcomes. All included studies had informative practice model designs, with interventions for drug-related problems including drug dose optimisation ( n = 8), reduced drug interaction ( n = 6) and adverse drug reaction reporting ( n = 3). Most studies ( n = 11) reported on symptom improvement, commonly nausea ( n = 7) and pain ( n = 5). Of four studies in radiotherapy cohorts, pharmacist involvement was associated with improved symptoms, satisfaction and wellbeing scores. CONCLUSION: Few studies have objectively assessed outpatient pharmacy cancer services, even fewer in the radiotherapy settings. Although the results support these services, significant heterogeneity and bias in the study designs prohibit robust conclusions and further controlled trials are required.

Survival difference according to mutation status in a prospective cohort study of Australian patients with metastatic non-small-cell lung carcinoma.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histological subtypes but also different molecular subtypes. AIM: To describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled in a prospective Thoracic Malignancies Cohort Study between July 2012 and August 2016 were selected. Patients underwent molecular testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangements, Kirsten rat sarcoma (KRAS), B-Raf proto-oncogene (BRAF) mutations and ROS1 gene rearrangements. Survival was calculated using the Kaplan-Meier method for groups of interest, and comparisons were made using the log-rank test. RESULTS: A total of 392 patients were included, 43% of whom were female with median age of 64 years (28-92). Of 296 patients tested, 172 patients (58%) were positive for an oncogenic driver: 81 patients (27%) were EGFR positive, 25 patients (9%) were ALK positive, 57 patients (19%) had KRAS mutation and 9 patients (3%) were ROS1 or BRAF positive. Patients with an actionable mutation (EGFR/ALK) had a survival advantage when compared with patients who were mutation negative (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.33-0.71; P < 0.01). Survival difference between mutation negative and mutation status unknown was not statistically significant when adjusted for confounding factors in a multivariate analysis (HR 1.29; 95% CI 0.97-1.78, P = 0.08). CONCLUSION: In this prospective cohort, the presence of an actionable mutation was the strongest predictor of overall survival. These results confirm the importance of molecular testing and suggest likely survival benefit of identification and treatment of actionable oncogenes.