Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients

<p>Abstract</p> <p>Background</p> <p>This retrospective study evaluated the impact of disease progression and of specific sites of metastasis on patient reported outcomes (PROs) that assess symptom burden and health related quality of life (HRQoL) in women with metastatic breast cancer (mBC).</p> <p>Methods</p> <p>HER-2 negative mBC patients (n = 102) were enrolled from 7 U.S. community oncology practices. Demographic, disease and treatment characteristics were abstracted from electronic medical records and linked to archived Patient Care Monitor (PCM) assessments. The PCM is a self-report measure of symptom burden and HRQoL administered as part of routine care in participating practices. Linear mixed models were used to examine change in PCM scores over time.</p> <p>Results</p> <p>Mean age was 57 years, with 72% of patients Caucasian, and 25% African American. Median time from mBC diagnosis to first disease progression was 8.8 months. Metastasis to bone (60%), lung (28%) and liver (26%) predominated at initial metastatic diagnosis. Results showed that PCM items assessing fatigue, physical pain and trouble sleeping were sensitive to either general effects of disease progression or to effects associated with specific sites of metastasis. Progression of disease was also associated with modest but significant worsening of General Physical Symptoms, Treatment Side Effects, Acute Distress and Impaired Performance index scores. In addition, there were marked detrimental effects of liver metastasis on Treatment Side Effects, and of brain metastasis on Acute Distress.</p> <p>Conclusions</p> <p>Disease progression has a detrimental impact on cancer-related symptoms. Delaying disease progression may have a positive impact on patients' HRQoL.</p

Validation of a patient satisfaction questionnaire for anemia treatment, the PSQ-An

BACKGROUND: Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment is limited by the lack of validated instruments. We developed and validated a new treatment-specific patient satisfaction instrument: the Patient Satisfaction Questionnaire for Anemia Treatment (PSQ-An). Treatment burden and overall satisfaction scales were designed for ease of use in clinical practice. METHODS: 312 cancer patients (141 breast, 69 gynecological, and 102 non-small cell lung) were targeted to complete the PSQ-An at 4 week intervals. Data from weeks 5 and 9 were analyzed. Patients also completed the MOS SF-36 Global Health assessment and questions concerning resources devoted to anemia treatment. Item reduction used endorsement rates, floor/ceiling effects, and item-item correlations. Factor analysis identified meaningful subscales. Test-retest reliability was assessed. Construct validity was tested, using Pearson's correlations, by comparing subscale scores to Global Health, hemoglobin levels, and resources devoted to anemia treatment. RESULTS: The overall response rate was 92.9% (264/284) at week 5. Most (84.2%) of the patients were female, and the mean (SD) age was 60.2 (± 11.8) years. Two distinct subscales were identified measuring treatment burden (7 items) and overall satisfaction (2 items). Test-retest reliability was examined (ICC: 0.45–0.67); both were internally consistent (alpha = 0.83). Both subscales exhibited convergent and divergent validity with independent measures of health. ANOVA results indicated that the PSQ-An Satisfaction subscale discriminated between 5 levels of MOS SF-36 Global Health (P = 0.006). CONCLUSION: The PSQ-An is a validated, treatment-specific instrument for measuring satisfaction with anemia treatment for cancer patients. PSQ-An subscales reflect the burden of injection anemia treatment on cancer patients and their assessment of the overall treatment value

Safety and Pharmacokinetics of Motesanib in Combination with Panitumumab and Gemcitabine-Cisplatin in Patients with Advanced Cancer

Purpose. The aim of this study was to assess the safety and tolerability of motesanib (an orally administered small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and Kit) when administered in combination with panitumumab, gemcitabine, and cisplatin. Methods. This was an open-label, multicenter phase 1b study in patients with advanced solid tumors with an ECOG performance status ≤1 and for whom a gemcitabine/cisplatin regimen was indicated. Patients received motesanib (0 mg [control], 50 mg once daily [QD], 75 mg QD, 100 mg QD, 125 mg QD, or 75 mg twice daily [BID]) with panitumumab (9 mg/kg), gemcitabine (1250 mg/m2) and cisplatin (75 mg/m2) in 21-day cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Results. Forty-one patients were enrolled and received treatment (including 8 control patients). One of eight patients in the 50 mg QD cohort and 5/11 patients in the 125 mg QD cohort experienced DLTs. The maximum tolerated dose was established as 100 mg QD. Among patients who received motesanib (n = 33), 29 had motesanib-related adverse events. Fourteen patients had serious motesanib-related events. Ten patients had motesanib-related venous thromboembolic events and three had motesanib-related arterial thromboembolic events, two of which were considered serious. One patient had a complete response and nine had partial responses as their best objective response. Conclusions. The combination of motesanib, panitumumab, and gemcitabine/cisplatin could not be administered consistently and, at the described doses and schedule, may be intolerable. However, encouraging antitumor activity was noted in some cases

An examination of health care utilization during the COVID-19 pandemic among women with early-stage hormone receptor-positive breast cancer

Background: Women undergoing treatment for breast cancer require frequent clinic visits for maintenance of therapy. With COVID-19 causing health care disruptions, it is important to learn about how this population’s access to health care has changed. This study compares self-reported health care utilization and changes in factors related to health care access among women treated at a cancer center in the mid-South US before and during the pandemic. Methods: Participants (N = 306) part of a longitudinal study to improve adjuvant endocrine therapy (AET) adherence completed pre-intervention baseline surveys about their health care utilization prior to AET initiation. Questions about the impact of COVID-19 were added after the pandemic started assessing financial loss and factors related to care. Participants were categorized into three time periods based on the survey completion date: (1) pre-COVID (December 2018 to March 2020), (2) early COVID (April 2020 – December 2020), and later COVID (January 2021 to June 2021). Negative binomial regression analyses used to compare health care utilization at different phases of the pandemic controlling for patient characteristics. Results: Adjusted analyses indicated office visits declined from pre-COVID, with an adjusted average of 17.7 visits, to 12.1 visits during the early COVID period (p = 0.01) and 9.9 visits during the later COVID period (p < 0.01). Hospitalizations declined from an adjusted average 0.45 admissions during early COVID to 0.21 during later COVID, after vaccines became available (p = 0.05). Among COVID period participants, the proportion reporting changes/gaps in health insurance coverage increased from 9.5% participants during early-COVID to 14.8% in the later-COVID period (p = 0.05). The proportion reporting financial loss due to the pandemic was similar during both COVID periods (34.3% early- and 37.7% later-COVID, p = 0.72). The proportion of participants reporting delaying care or refilling prescriptions decreased from 15.2% in early-COVID to 4.9% in the later-COVID period (p = 0.04). Conclusion: COVID-19 caused disruptions to routine health care for women with breast cancer. Patients reported having fewer office visits at the start of the pandemic that continued to decrease even after vaccines were available. Fewer patients reported delaying in-person care as the pandemic progressed.National Cancer Institute ; Division of Cancer Prevention, National Cancer Institute ; Center for Strategic Scientific Initiatives, National Cancer Institute ; Division of Cancer Epidemiology and Genetics, National Cancer Institut

NEOADJUVANT WEEKLY NAB-PACLITAXEL PLUS CARBOPLATIN FOLLOWED BY DOXORUBICIN PLUS CYCLOPHOSPHAMIDE WITH BEVACIZUMAB ADDED CONCURRENTLY TO CHEMOTHERAPY FOR OPERABLE TRIPLE-NEGATIVE INVASIVE BREAST CANCER

Purpose: This phase II neoadjuvant study investigated whether nab paclitaxel, carboplatin and bevacizumab given before neoadjuvant doxorubicin/cyclophosphamide (AC) produced higher pathologic complete response (pCR) rates in triple- negative breast cancer (TNBC) compared with historical results achieved with standard anthracycline/taxane regimens. Patients and Methods: Eligible patients with operable TNBC ≥2 cm received four cycles of carboplatin (area under the curve 6, day 1) plus nab-paclitaxel (100 mg/m2, days 1, 8 and 15) every 28 days, followed by four 14-day cycles of AC neoadjuvantly, with bevacizumab 10 mg/kg every 14 days for the rst 6 cycles of neoadjuvant chemotherapy, resuming postoperatively to complete 1 year of antibody treatment. In breast pCR and pCR (breast + nodes) were primary and secondary endpoints, respectively. Results: Due to slow accrual, the study was closed after enrollment of 42 of 60 planned patients. Of the 38 patients who underwent surgery (ef cacy population), 22 (58%) achieved an in-breast pCR and 19 (50%) achieved a pCR (breast + nodes). Neutropenia was the most common Grade 3/4 adverse event (57% Grade 3 and 31% Grade 4), but only 1 patient required hospitalisation and IV antibiotics for neutropenic fever. Other Grade 3/4 events included anaemia (24%), thrombocytopenia (29%) and peripheral neuropathy (Grade 3, 5%). Conclusion: Our results demonstrate a substantially higher pCR rate, both in-breast and breast + nodes, with the combination of nab paclitaxel plus carboplatin followed by AC, with concurrent bevacizumab, versus historic pCR rates with anthracycline-taxane regimens alone, supporting further investigation of this regimen, preferably in molecularly driven subsets, for the neoadjuvant treatment of patients with TNBC. Key words: Bevacizumab, breast cancer, carboplatin, nab-paclitaxel, neoadjuvant, triple-negative

Lapatinib plus Letrozole as First-Line Therapy for HER-2+ Hormone Receptor–Positive Metastatic Breast Cancer

Reported are results from a subgroup analysis of postmenopausal women with hormone receptor–positive human epidermal growth factor receptor 2–positive metastatic breast cancer from a phase III trial of letrozole plus placebo versus letrozole plus lapatinib. The combination was well tolerated and more efficacious than letrozole alone

Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non–Small-Cell Lung Cancer

IntroductionThere is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non–small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed.MethodsIn this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non–small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64–68 Gy over days 1–45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate.ResultsFrom June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5–60.0%); PC: 58.4% (95% CI, 42.6–71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0–64.8%); PC: 55.8% (95% CI, 38.0–70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0–12.6 months); PC: 13.1 months (95% CI, 8.3–not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9–NE); PC: 27.0 (95% CI, 23.2–NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy.ConclusionsBecause of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated

Experiencing neutropenia: Quality of life interviews with adult cancer patients

BACKGROUND: Neutropenia is a common toxicity in chemotherapy but detailed information about how neutropenia is associated with changes in patients' quality of life is not readily available. This prospective study interviewed patients with grade 4 neutropenia to provide qualitative information on patients' experience of developing and coping with grade 4 neutropenia during a cycle of chemotherapy. METHODS: A sample of 34 patients who developed grade 4 neutropenia during the first cycle of chemotherapy completed a total of 100 structured clinical interviews. Interviews were transcribed, and 2 raters inductively developed 5 broad categories comprising 80 specific complaint domains nominated by patients. Thirty-five patient-nominated problems were mentioned in 5% or more of the interviews. RESULTS: Fatigue was the most common physical symptom. Interference in daily routine, negative self-evaluation, negative emotion, and social isolation were other common complaints associated with neutropenia. CONCLUSION: Neutropenia is associated with a number of negative experiences among cancer patients undergoing chemotherapy, and these negative experiences have an adverse effect on the patient's quality of life. Oncology nurses can play a key role in helping patients manage adverse effects to maintain their quality of life

Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase III BEACON trial

Background: Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician’s choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. Patients and methods: HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared. Results: Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P &lt; 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of −9.4 and −10.8 points, respectively. Conclusion: There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression. Study number: NCT01492101