Pertuzumab study in the neoadjuvant setting for HER2-positive nonmetastatic breast cancer in Australia (PeRSIA).

The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.

The Elderly Functional Index (ELFI), a patient-reported outcome measure of functional status in patients with cancer: a multicentre, prospective validation study.

BACKGROUND: Functional assessment of patients with cancer can be challenging and is often undertaken by the clinician with minimal direct input from the patient. We developed and aimed to validate the Elderly Functional Index (ELFI), a composite measure of self-reported functioning in older patients with cancer. METHODS: In this multicentre, prospective validation study, we validated ELFI in adult patients attending five oncology practices in Australia. ELFI is a 12-item composite measure of self-reported functioning derived from functional scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ): physical, role, and social functioning, and mobility. For evaluation of validity and internal consistency, participants self-completed ELFI, cognitive functioning and emotional functioning scales of the EORTC QLQ Core-30, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), instrumental activities of daily living (IADL), and Clinical Frailty Scale (CFS) at baseline. For evaluation of test-retest reliability, participants opted in to repeat ELFI, cognitive functioning scale, emotional functioning scale, and ECOG-PS 1 week later, as well as completing the Global Rating of Change. Internal consistency reliability was assessed using Cronbach's α and test-retest reliability was assessed using intraclass correlation (ICC). We assessed ELFI for convergent and discriminant validity (Spearman's r), known-groups validity (ANOVA), and structural validity (exploratory factor analysis). FINDINGS: Between May 6 and Dec 15, 2017, 877 participants with cancer returned a total of 869 baseline questionnaires and 482 retest questionnaires. 621 (71%) participants (192 [31%] aged ≥70 years) were included in evaluations of validity and internal consistency and 278 (32%) participants (106 [38%] aged ≥70 years) in evaluations of test-retest reliability. ELFI demonstrated excellent internal consistency reliability (Cronbach's α=0·93 for all participants; p<0·0001) and test-retest reliability (overall ICC 0·90, 95% CI 0·87-0·92; p<0·0001). Hypotheses regarding convergent and discriminant validity were confirmed, with all item-scale correlations exceeding 0·40 except for one on the physical functioning scale. ELFI was better than its component scales and other function measures at differentiating between groups with different function and frailty scores (known-groups validity). Exploratory factor analysis provided empirical support to the structural validity of ELFI. Strong correlation was observed between ELFI and its component scales (r ranging from 0·67 to 0·79), ECOG-PS (-0·79), IADL (0·69), and CFS (-0·73). INTERPRETATION: ELFI is a validated and simple person-reported multidimensional measure of functional status, which captures broad dimensions of functioning. ELFI has enhanced statistical efficiency relative to its components, reducing the sample size required to detect a given effect. ELFI could be used as a clinical trial endpoint to assess functional domains of health-related quality of life. FUNDING: National Health and Medical Research Council, Monash University, Eastern Health.

Understanding Patients' Attitudes Toward Cancer Multidisciplinary Meetings: A Mixed Methods Study.

PURPOSE: Multidisciplinary cancer meetings (MDMs) are an integral component of quality care; however, little research exists regarding patients' views on this model of care. We aimed to explore and understand the attitudes of patients toward MDMs. METHODS: A mixed methods exploratory design was used. Qualitative data from patients with a current or previous diagnosis of cancer were collected and analyzed using a grounded theory approach. Results informed the development of a questionnaire survey that was administered to patients with a current or previous diagnosis of cancer. Results were analyzed using descriptive statistics. RESULTS: Nine patients participated in 3 focus groups, and 152 patients (response rate, 90%) completed the questionnaire. Patients were strongly supportive of MDMs and thought that all patients with cancer should be routinely discussed. More than 90% of surveyed patients believed MDMs were reassuring, meant all treatment modalities were considered, and led to evidence-based treatment recommendations. Patients wanted MDMs to focus on medical treatment planning rather than psychosocial issues, and 87% regarded the meeting as confidential. Patients described a preference for doctor-led decision making, and most (84%) wanted MDM treatment decisions to be discussed with them in a subsequent consultation, with 73% of patients also wanting this in a written format. CONCLUSION: Patients strongly endorse MDMs as a means to develop an evidence-based, medical treatment plan agreed to by consensus. They want to be purposely informed of the meeting and its outcomes. Results from this study can help inform future guidelines on the conduct of MDMs.

Comprehensive geriatric assessment is useful in an elderly Australian population with diffuse large B-cell lymphoma receiving rituximab-chemotherapy combinations.

Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy-associated toxicities. We describe the morbidity of rituximab-chemotherapy combinations among 205 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients aged ≥60 years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively-assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy-three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166 (23%) had chemotherapy delays and 26/198 (13%) ceased therapy early. CGA was associated with pre-emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three-year overall survival (OS) of CGA-fit, CGA-unfit and CGA-frail patients was 82%, 60% and 53%, respectively. Three-year progression-free survival (PFS) of CGA-fit, CGA-unfit and CGA-frail patients was 66%, 58% and 46%, respectively. OS of CGA-fit patients was not statistically different from CGA-unfit patients, but was superior to CGA-frail patients (hazard ratio 2·892, 95% confidence interval 1·275-6·559, P = 0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA-adapted treatment strategies minimize morbidity and improves survival.

Utilisation of geriatric assessment in oncology - a survey of Australian medical oncologists.

INTRODUCTION: Geriatric assessment (GA) is a multidimensional health assessment of the older person to evaluate their physical and cognitive function, comorbidities, nutrition, medications, psychological state, and social supports. GA may help oncologists optimise care for older patients with cancer. The aim of this study was to explore the views of Australian medical oncologists regarding the incorporation of geriatric screening tools, GA and collaboration with geriatricians into routine clinical practice. METHODS: Members of the Medical Oncology Group of Australia were invited to complete an online survey that evaluated respondent demographics, practice characteristics, treatment decision-making factors, use of GA, and access to geriatricians. RESULTS: Sixty-nine respondents identified comorbidities, polypharmacy, and poor functional status as the most frequent challenges in caring for older patients with cancer. Physical function, social supports and nutrition were the most frequent factors influencing treatment decision-making. The majority of respondents perceived value in GA and geriatrician review, although access was a barrier for referral. Such services would need to be responsive, providing reports within two weeks for the majority of respondents. CONCLUSION: Despite an emerging evidence base for the potential benefits of GA and collaboration with geriatricians, medical oncologists reported a lack of access but a desire to engage with these services.

Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma.

The effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared with that of tumors containing BRAF(V600E) mutations and tumors wild type for both (WT). Clinical outcome data were obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAF(V600E) were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. Seventy-five percentage of NRAS mutations occurred in tumors >1 mm thick (BRAF(V600E) 40%, WT 34%); 75% of NRAS mutations had >1 mitosis/mm(2) (BRAF(V600E) 40%, WT 55%). When compared to WT, multivariate analysis of melanoma-specific survival (MSS) identified NRAS mutations as an adverse prognostic factor [hazard ratio (HR) 2.96; P = 0.04] but not BRAF(V600E) mutations (HR 1.73; P = 0.23). NRAS mutations were associated with thicker tumors and higher rates of mitosis when compared to BRAF(V600E) and WT melanoma and independently of this, with shorter MSS.

What should a support program for people with lung cancer look like? Differing attitudes of patients and support group facilitators.

INTRODUCTION: Patients with lung cancer have higher levels of unmet need for psychosocial support than those with other cancers. However, uptake of existing support programs by patients with lung cancer is low. We explored this issue by seeking the views of patients and support group facilitators. METHODS: Surveys of a convenience sample of 100 patients with lung cancer and all support group facilitators registered with Cancer Council Victoria (n = 145) were performed. Respondents were asked about preferred content, location, running, and potential barriers to attendance of a lung cancer support program. RESULTS: The response rate from facilitators was 51%. Fifty-three percent of patients reported willingness to attend a support program, although only 12% had previously attended a group. Patients showed a preference for any program to be held at a hospital (p = 0.01), whereas facilitators preferred a community setting (p < 0.001). Patients preferred facilitation by a health professional, rather than a volunteer p < 0.001), whereas facilitators preferred a volunteer. Patients preferred sessions primarily focused on cancer information provision rather than emotional support, whereas facilitators rated emotional support as highly as cancer information. Overall, patients perceived fewer barriers to attendance than facilitators. Both agreed that a group environment, discussing their cancer, parking, and travel were barriers to attendance. CONCLUSIONS: Disparities in the views of patients and facilitators about the preferred location, type of facilitator, and content of a support program may in part explain the poor uptake of existing support programs by patients with lung cancer and should be considered in the design of future programs.

Team dynamics, decision making, and attitudes toward multidisciplinary cancer meetings: health professionals' perspectives.

PURPOSE: Multidisciplinary cancer care is a standard feature of high quality care. In many centers, the multidisciplinary meeting (MDM) is an integral component. A qualitative study was performed to explore health professionals' attitudes towards this model of care, the decision making processes, and dynamics among team members. METHODS: A series of focus groups was conducted with health professionals who attend MDMs at our institution. Focus groups followed a semistructured format with open-ended questions. A thematic analysis was performed. RESULTS: Four focus groups were held, attended by 23 participants including allied health professionals, specialist nurses, medical oncologists, and surgeons. All participants believed the primary objective of the MDM was to develop an individualized treatment plan. Several other key themes emerged. The MDM provided opportunities to improve communication, efficiency, and education as well as enhance professional relationships. Medical information was prioritized ahead of psychosocial details, with allied health professionals describing difficulty contributing to MDM discussion. Patient attendance at MDMs was opposed by health professionals because of concerns about the patient's ability to cope with the information discussed and the effect their presence would have on the dynamics of the decision-making process. CONCLUSION: Health professionals endorse MDMs as a useful tool in treating patients with cancer. Within this forum, both opportunities and constrains exist, with many benefits extending beyond the meeting itself into other clinical areas. Further study is warranted to establish an evidence base to ensure that both the possibilities and the limitations of this model of care are fully understood.

Use of ibandronate in the prevention of skeletal events in metastatic breast cancer.

Bone metastasis from breast cancer often cause significant morbidity including pain, impaired mobility, pathological fracture, and spinal cord compression. Bisphosphonates play an important role in preventing these skeletal related events and are the standard of care for patients with bone metastasis from breast cancer. Ibandronate is a highly potent bisphosphonate available in both intravenous and oral preparations. It has been shown in clinical trials to be effective in reducing skeletal complications and also significantly improve quality of life up to 96 weeks. Unlike other intravenous bisphosphonates, ibandronate has minimal renal toxicity, allowing safe outpatient administration, reducing the need for hospital attendance and safety monitoring. Early trials have shown ibandronate may also be effective in high doses for palliation of opioid-resistant pain from bone metastasis, and as a second-line agent in patients developing a skeletal complication whilst receiving another bisphosphonate.