Optimising oncology drug expenditure in Ireland.

A combination of improvements in patient survival, increasing treatment duration, and the development of more expensive agents has led to a doubling of per-capita spending on cancer medicines in Ireland (2008-2018). Despite this, access to new drugs is poor in comparison to other EU countries. We examine methods to optimise oncology drug spending to facilitate access to newer anticancer agents. Key targets for spending optimisation (biosimilar use, clinical trials and expanded access programs, waste reduction, avoidance of futile treatment, and altered drug scheduling) were identified through an exploratory analysis. A structured literature search was performed, with a focus on articles relevant to the Irish Healthcare system, supplemented by reports from statutory bodies. At the present time, EMA-approved agents are available once approved by the NCPE. Optimising drug costs occurs through guideline-based practice and biosimilar integration, the latter provides €80 million in cost savings annually. Access to novel therapies can occur via over 50 clinical trials and 28 currently available expanded access programmes. Additional strategies include reversion to weight-based immunotherapy dosing, potentially saving €400,000 per year in our centre alone, vial sharing, and optimisation of treatment schedules. A variety of techniques are being employed by oncologists to optimise costs and increase access to innovation for patients. Use of biosimilars, drug wastage, and prescribing at end of life should be audited as key performance indicators, which may lead to reflective practice on treatment planning. Such measures could further optimise oncology drug expenditure nationally facilitating approval of new agents.

Dietary supplement beliefs and use patterns among Irish patients with early-stage breast cancer.

BACKROUND: Level one evidence reported poorer outcomes among patients taking dietary supplements after breast cancer (BC) diagnosis. METHODS: We evaluated dietary supplement behaviours among adult BC patients via questionnaire. Sociodemographic data, supplement use, attitudes, and healthcare provider (HCP) advice were analysed. RESULTS: Of 185 participants, 45% were regular supplement users following diagnosis. Regular supplement use was associated with higher education level (p = 0.05). The majority perceived supplements to be safe. Over half reported not receiving advice from HCPs. CONCLUSION: In summary, supplement use is prevalent among BC patients. Development of guidelines in relation to safe use of dietary supplements after cancer diagnosis is crucial.

Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial).

Predictive biomarkers of response to human epidermal growth factor receptor 2 (HER2)-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early declines in tumor SUVs corrected for lean body mass (SULmax) on 18F-FDG PET/CT predicted a pathologic complete response (pCR) to HER2 therapy with neoadjuvant trastuzumab and pertuzumab (HP) without chemotherapy in estrogen receptor (ER)-negative, HER2-positive breast cancer. We hypothesized that 18F-FDG PET/CT SULmax parameters would predict recurrence-free survival (RFS) and overall survival (OS). Methods: Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (n = 88). pCR after HP alone was 22% (18/83), additional nonstudy neoadjuvant therapy was administered in 28% (25/88), and the majority received adjuvant therapy per physician discretion. 18F-FDG PET/CT was performed at baseline and at cycle 1, day 15 (C1D15). RFS and OS were summarized using the Kaplan-Meier method and compared between subgroups using logrank tests. Associations between 18F-FDG PET/CT (≥40% decline in SULmax between baseline and C1D15, or C1D15 SULmax ≤ 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. Results: Median follow-up was 53.7 mo (83/88 evaluable), with 6 deaths and 14 RFS events. Estimated RFS and OS at 3 y was 84% (95% CI, 76%-92%) and 92% (95% CI, 87%-98%), respectively. A C1D15 SULmax of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11-1.05; P = 0.06) and OS (HR, 0.14; 95% CI, 0.01-0.85; P = 0.03), the latter statistically significant. The association of an SULmax decline of at least 40% (achieved in 59%) with RFS and OS did not reach statistical significance. pCR was associated with improved RFS (HR, 0.25; 95% CI, 0.01-1.24; P = 0.10) but did not reach statistical significance. Conclusion: For the first time, we report a potential association between a C1D15 SULmax of 3 or less on 18F-FDG PET/CT and RFS and OS outcomes in patients with ER-negative, HER2-positive breast cancer receiving neoadjuvant HP alone. If confirmed in future studies, this imaging-based biomarker may facilitate early individualization of therapy.

Metastatic gastroesophageal cancer in older patients - is this patient cohort represented in clinical trials?

BACKGROUND: Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer. METHODS: A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model. RESULTS: Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18-94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65-80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). CONCLUSIONS: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.

COVID-19-related mortality in cancer patients in an Irish setting.

BACKGROUND: The COVID-19 pandemic has impacted significantly on healthcare across the globe. It has been reported to have higher incidence and be associated with worse outcomes in patients with cancer. AIM: To examine the characteristics of patients with cancer who were diagnosed with COVID-19 and to identify factors which may predict a poorer outcome. METHODS: Patients attending oncology services in Beaumont Hospital who were diagnosed with COVID-19 between March and May 2020 were included. Demographics and outcomes were determined by chart review. RESULTS: Twenty-seven patients were included in the study. The median age was 62; 59% were male. Ten patients (37%) died all of whom had metastatic or incurable locally advanced disease. Patients with lung cancer had a higher rate of COVID-19 and poorer outcomes. Those with a performance status (PS) ≥ 3 were more likely to die than those with PS ≤ 2. Compared to those who recovered, patients who died had a higher number of organs affected by cancer and a higher mean Palliative Prognostic Score. CONCLUSION: Patients attending oncology services during the initial phase of the COVID-19 pandemic had an increased rate of SARS-CoV-2 infection and a higher mortality rate than the general population. Those who died had more advanced cancer as demonstrated by poorer performance status, a greater burden of metastatic disease and a higher Palliative Prognostic Score.

Delivery of systemic anti-cancer therapy during the COVID-19 pandemic.

BACKGROUND: The first confirmed case of COVID-19 in Ireland was on February 29th 2020. From March until late April, the number of cases increased exponentially. The delivery of anti-cancer therapy during the COVID-19 pandemic was extremely challenging. In order to balance the benefits of continuing anti-cancer therapy with the associated increased hospital visits, combined with the risk of COVID-19 infection, we undertook a series of system changes in the delivery of cancer care. METHODS: Patients who attended our dayward over a 4-month period were included. Data were obtained from patient and chemotherapy prescribing records. Patients were screened for symptoms of COVID-19 at two separate timepoints: prior to their visit via telephone, and using a symptom questionnaire on arrival at the hospital. If patients displayed COVID-19 symptoms, they were isolated and a viral swab arranged. RESULTS: A total of 456 patients attended from January 1st to April 30th. The numbers of visits from January to April were 601, 586, 575, and 607, respectively. During this period, there were 2369 patient visits to the dayward and 1953 (82%) intravenous regimens administered. Of the 416 visits that did not lead to treatment, 114 (27%) were scheduled non-treatment review visits, 194 (47%) treatments were held due to disease-related illness, and 108 (26%) treatments were held due to treatment-related complications. Screening measurements were implemented on March 18th due to rising COVID-19 prevalence in the general population. Overall, 53 treatments were held due to the screening process: 19 patients (36%) elicited COVID-19 symptoms via telephone screening; 34 patients (64%) were symptomatic in our pre-assessment area and referred for swabs, of which 4 were positive. Those with a negative swab were rescheduled for chemotherapy the following week. CONCLUSIONS: With careful systematic changes, safe and continued delivery of systemic anti-cancer therapy during the COVID-19 pandemic is possible.

Prognostic factors influencing survival following re-resection for isocitrate dehydrogenase (IDH) -wildtype glioblastoma multiforme - Data from a national neuro-oncology registry.

The role of surgical resection in recurrent Glioblastoma Multiforme (GBM) remains unclear. We aimed to investigate survival outcomes and associated prognostic factors in patients undergoing surgical re-resection for recurrent IDH-wildtype GBM in a national neuro-oncology center. We evaluated all patients who underwent re-resection for recurrent GBM following adjuvant treatment between 2015 and 2018. 32 patients were eligible for inclusion. 19 (59%) were male,median age at re-resection was 53. Median time from initial surgery to re-resection was 13.5 months. Median overall survival (OS) was 28.6 months from initial surgery and 9.5 months from re-resection. MGMT methylation was significantly associated with improved OS from initial surgery, 40 months versus 19.1 months, (p = 0.004), and from re-resection, 9.47 months versus 6.93 months, (p = 0.028). A late re-resection was associated with improved OS compared to an early re-resection, 44.1 months versus 15.7 months, (p = 0.002). There was a trend for improved outcomes in younger patients, median OS from initial surgery 44.1 months for <53 years compared to 21.7 months for patients ≥53, (p = 0.099). Higher Karnofsky Performance Status (KPS) at re-resection was associated with improved median OS, 9.5 months versus 4.1 months for KPS ≥70 and <70 respectively, (p = 0.013). Furthermore, there was a trend for improved OS with greater extent of re-resection, however this did not reach statistical significance, possibly due to small sample size. Re-resection for recurrent GBM was associated with improved OS in those with good performance status and could be considered in carefully selected cases.

One year of procarbazine lomustine and vincristine is poorly tolerated in low grade glioma: a real world experience in a national neuro-oncology centre.

BACKGROUND: Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice. METHODS: We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities. RESULTS: Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia. CONCLUSION: Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.

Chemotherapy in the Covid-19 era: the patient's perception.

BACKGROUND: The Covid-19 pandemic poses significant challenges for the management of patients with cancer. In our institution, we adapted our delivery of outpatient systemic anti-cancer therapy (SACT) by introducing a number of 'risk-reducing' measures including pre-assessment screening. AIMS: We sought to evaluate the experience and perceptions of patients with cancer undergoing SACT during the Covid-19 pandemic. METHODS: Patients on SACT during the Covid-19 pandemic were eligible for participation. Data were collected by anonymous survey over a 1 week period during the most intensive phase of government restrictions. Patients were asked questions under three headings: perceived risk of infection exposure, changes to treatment plan and psychological impact of Covid-19. RESULTS: One hundred patients were assessed, 60% were male, 41% were > 65 years of age and 67% had advanced cancer. Eleven percent of patients were living alone. Fifty-seven percent reported feeling at increased risk in general of contracting Covid-19. Sixty-eight percent of patients did not feel worried about contracting Covid-19 in the hospital. Ninety-two percent of patients reported wanting to continue on SACT as originally planned. Fifty-eighty percent felt isolated and 40% reported increased anxiety. CONCLUSION: Though patients on active treatment for cancer during the Covid-19 pandemic reported increased anxiety and feelings of isolation due to Covid-19, the majority of patients wanted to continue SACT as originally planned. Patients would benefit from enhanced psycho-oncological supports in the event of a prolonged Covid-19 pandemic.

Patient demographics and management challenges in an Irish symptomatic breast cancer unit.

BACKGROUND: Breast cancer is the most common cancer in women. Beaumont Hospital is a nationally designated symptomatic breast cancer unit, independent of the national screening programme, BreastCheck. AIMS: We hypothesised that patients attending symptomatic breast cancer units differ from national registry data and aimed to characterise this in a retrospective study. METHODS: A prospective database of patients diagnosed with breast cancer was maintained between 2014 and 2017. Multiple patient and tumour demographics were analysed retrospectively and compared with data from the National Cancer Registry. RESULTS: In total, 944 patients were diagnosed with breast cancer, 379 (40%) were aged < 50, 206 (22%) 50-64, 208 (22%) 65-75 and 151 (16%) > 75 years respectively. Expectedly, older patients (≥ 65 years) had a higher proportion of oestrogen receptor-positive, HER2-negative breast cancer (72%). Triple negative breast cancer was relatively more common (17%) among younger patients. These patients received more intensive chemotherapy: 118 (64%) received combination anthracycline-taxane chemotherapy, in comparison with only 14 (21%) of older patients. Patients generally presented at a later stage compared with national registry data: stage II 491 (52%) and stage III 179 (19%) versus stage II (50%) and stage III (13%). CONCLUSION: Patients attending the symptomatic breast cancer unit Beaumont Hospital have different demographics compared with the national registry data. This presents particular challenges for management.

Induction treatment prior to chemoradiotherapy in nasopharyngeal carcinoma: triplet or doublet chemotherapy?

Nasopharyngeal carcinoma is a malignancy that is endemic in Asia. The current standard of care for loco-regionally advanced disease is platinum-based concurrent chemo-radiotherapy. However, relapse remains a common issue. Phase II trials have shown encouraging results when induction chemotherapy with gemcitabine and cisplatin is added to chemo-radiation. In a major recent advance, a phase III trial demonstrated significantly improved recurrence-free survival (RFS) and overall survival (OS) for this approach compared to chemo-radiotherapy alone. Results from this trial showed a 4.3% improvement in OS over standard therapy at 3 years, (94.6% vs 90.3%), with an expected increase in acute adverse events. In this article, we put this treatment in context of other proven approaches in nasopharyngeal carcinoma. There is a lack of comparative data in relation to the optimal induction regimen. It remains to be seen whether or not treatment with the gemcitabine-cisplatin doublet differs significantly from the established induction triplet of docetaxel, cisplatin and fluorouracil (TPF) with regard to efficacy or toxicity, but it is likely that many more patients would tolerate gemcitabine-cisplatin compared to TPF. Immunotherapy could prove a promising strategy in combination with induction therapy. Future treatment strategies for nasopharyngeal carcinoma will likely adopt a more personalised approach.