Standard-Dose Osimertinib in EGFR-Mutated Non-Small-Cell Lung Adenocarcinoma With Leptomeningeal Disease.

PURPOSE: Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non-small-cell lung cancer who developed LMD and were subsequently treated with osimertinib. METHODS: We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used. RESULTS: Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months). CONCLUSION: There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.

Use of clinical quality indicators to improve lung cancer care in a regional/rural network of health services.

PROBLEM: Optimal lung cancer care requires multidisciplinary team input, with access to specialised diagnostic and therapeutic services that may be limited in rural or regional areas and impact clinical outcomes. Clinical quality indicators can be used to measure the quality of care delivered to patients with lung cancer in a region and identify areas for improvement. We describe the implementation of internationally recognised clinical quality indicators for lung cancer care in the Barwon South Western region. DESIGN: The consensus of an expert panel was used for the selection of clinical quality indicators. The data were retrospectively collected from the Evaluation of Cancer Outcomes Barwon South West Registry, which systematically records detailed information on all new patients with cancer in the region. SETTING: Region-based health service. KEY MEASURES FOR IMPROVEMENT: Adherence to clinical quality indicator targets. STRATEGIES FOR CHANGE: Clinical quality indicators, which fall short of the expected targets, highlight areas for improvement in the service provided to patients with lung cancer. These results have prompted changes in the service offered to these patients, such as the introduction of a multidisciplinary lung cancer clinic. EFFECTS OF CHANGE: The multidisciplinary lung cancer clinic has streamlined the access to lung cancer services, including specialist consultations, diagnostics and therapeutic services, in a regional setting. Ongoing data collection is required to determine the effect of such changes on adherence to clinical quality indicator targets. LESSONS LEARNT: The regular monitoring of clinical quality indicators serves as a useful method of quality assurance in the care of patients with lung cancer. We expect these clinical quality indicators to also be used by other health services to analyse and improve services provided to patients with lung cancer.

Development of a cognitive behavioural therapy-based guided self-help intervention for adults with intellectual disability.

BACKGROUND: Despite strong evidence for cognitive behaviour therapy (CBT) in treating mental health, its use, thus far, has been limited for people with intellectual disabilities. This study describes a CBT-based guided self-help (CBT-GSH) manual for individuals with intellectual disability, and focus groups explore the views of clinicians, therapists, support staff and managers. MATERIAL AND METHODS: Using a qualitative methodology, an expert team adapted the manual. Focus groups provided feedback, followed by thematic content analysis for modifications. RESULTS: Participants supported using the manual, with varying views about the delivery. Quality of relationships and competence of the administrator determined the best person to deliver the treatment. Heterogeneity in the intellectual disability population was a challenge to delivering manual-based interventions. Participants made suggestions about language and organization. CONCLUSIONS: Amendments were made to the manual in line with expert feedback. An evaluation is warranted to test for feasibility, delivery, acceptability and efficacy.

Epidermal growth factor receptor-tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung: a meta-analysis.

AIM: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are well established in treating metastatic pulmonary adenocarcinoma, especially patients with activating EGFR mutations. EGFR mutations are rare in pulmonary squamous cell carcinomas (SCCs). There are conflicting data supporting the efficacy of EGFR-TKIs in advanced lung SCC. We analyzed the impact of EGFR-TKIs on progression-free survival (PFS) and overall survival (OS) in unselected patients with lung SCC. METHODS: We searched for randomized controlled trials (RCTs) comparing EGFR-TKIs alone with placebo in patients with metastatic non-small cell lung cancer. RCTs in all settings (front line/maintenance/subsequent) were included. The primary outcome was OS in the SCC population. We used published hazard ratios (HRs), and when unavailable, unpublished data were sought. Pooled estimates of treatment effect on OS and PFS were calculated using the fixed-effects inverse variance weighted method. RESULTS: Eight eligible RCTs were included: 2 first-line, 6 second-line or beyond, evaluating 1781 patients. Data were available for OS in four studies (second-line; N=1420) and for PFS in four studies (3 second-line, 1 first-line; N=788). EGFR-TKIs significantly prolonged OS with a HR of 0.88 (95% confidence interval [CI] 0.78-1.00, P=0.04), and significantly prolonged PFS with a HR of 0.77 (95% CI 0.65-0.92, P=0.004). CONCLUSION: EGFR mutations are rare in lung SCC. However, EGFR-TKIs have a modest therapeutic effect compared to placebo in unselected patients with advanced pulmonary SCC, and can be considered in these patients. EGFR-mutation-independent mechanisms may explain efficacy of EGFR inhibitors in this setting.

Machine-learning prediction of cancer survival: a retrospective study using electronic administrative records and a cancer registry.

OBJECTIVES: Using the prediction of cancer outcome as a model, we have tested the hypothesis that through analysing routinely collected digital data contained in an electronic administrative record (EAR), using machine-learning techniques, we could enhance conventional methods in predicting clinical outcomes. SETTING: A regional cancer centre in Australia. PARTICIPANTS: Disease-specific data from a purpose-built cancer registry (Evaluation of Cancer Outcomes (ECO)) from 869 patients were used to predict survival at 6, 12 and 24 months. The model was validated with data from a further 94 patients, and results compared to the assessment of five specialist oncologists. Machine-learning prediction using ECO data was compared with that using EAR and a model combining ECO and EAR data. PRIMARY AND SECONDARY OUTCOME MEASURES: Survival prediction accuracy in terms of the area under the receiver operating characteristic curve (AUC). RESULTS: The ECO model yielded AUCs of 0.87 (95% CI 0.848 to 0.890) at 6 months, 0.796 (95% CI 0.774 to 0.823) at 12 months and 0.764 (95% CI 0.737 to 0.789) at 24 months. Each was slightly better than the performance of the clinician panel. The model performed consistently across a range of cancers, including rare cancers. Combining ECO and EAR data yielded better prediction than the ECO-based model (AUCs ranging from 0.757 to 0.997 for 6 months, AUCs from 0.689 to 0.988 for 12 months and AUCs from 0.713 to 0.973 for 24 months). The best prediction was for genitourinary, head and neck, lung, skin, and upper gastrointestinal tumours. CONCLUSIONS: Machine learning applied to information from a disease-specific (cancer) database and the EAR can be used to predict clinical outcomes. Importantly, the approach described made use of digital data that is already routinely collected but underexploited by clinical health systems.

Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

UNLABELLED: Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. RESULTS: All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. CONCLUSION: In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

Randomized phase 2 sequencing and pharmacokinetic study of gemcitabine and oxaliplatin in advanced non-small cell lung cancer.

AIM: This multicentre phase II trial examined the combination of gemcitabine and oxaliplatin in patients with advanced non-small cell lung cancer (NSCLC). The effect of sequence administration was randomized and pharmacokinetics (PK) assessed. METHODS: Eligible patients had stage IIIB or IV or recurrent NSCLC, no prior chemotherapy, World Health Organization performance status ≤2 and measurable disease. Treatment comprised: gemcitabine (1250 mg/m(2)) and oxaliplatin (70 mg/m(2)), each given on days 1 and 8 of a 21-day cycle. Patients were randomized 1:1 to the sequencing of the two drugs for the duration of their treatment. The primary end-point was response rate (RR). Secondary end-points included progression-free survival (PFS), overall survival (OS), toxicity, PK and the effect of drug sequencing. RESULTS: A total of 46 patients were enrolled of whom 43 were evaluable for response. Overall 13 patients (30%) achieved a partial response, PFS was 4.2 months (95% CI 2.8-5.8 months), and OS was 6.8 months (95% CI 4.4-10.1 months). There was only one case of grade 3 neurosensory toxicity despite a median cumulative oxaliplatin dose in excess of 500 mg/m(2) . No differences in clinical or PK end-points were observed between the two different sequencing arms. CONCLUSION: This oxaliplatin and gemcitabine schedule has shown activity in advanced NSCLC with modest toxicity. Neither clinical nor PK outcomes were influenced by the sequencing of these agents, although definite conclusions are limited by small patient numbers. The favorable toxicity profile of this doublet, in light of an encouraging RR, warrants its further investigation in NSCLC.

Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study.

PURPOSE: To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial. PATIENTS AND METHODS: Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL). RESULTS: Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups. CONCLUSION: Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.