Patient-reported symptom burden in patients with rare cancers receiving pembrolizumab in a phase II Clinical Trial.

Patients with rare solid tumors treated on early phase trials experience toxicities from their tumors and treatments. However, limited data exist to describe the detailed symptom burden suffered by these patients, particularly those with rare solid tumors treated with immunotherapy. We performed a prospective longitudinal study to capture patient-reported symptom burden. Patients completed the validated MD Anderson Symptom Inventory (MDASI)-Immunotherapy with 20 symptoms including 7 immunotherapy-specific items and 6 interference items at baseline and weekly thereafter for up to 9 weeks. Symptoms and interference were rated on 0-10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Group-based trajectory modelling determined higher and lower symptom groups. A total of 336 MDASI questionnaires were completed by 53 patients (mean age 55.4y, 53% male) with advanced rare cancers receiving pembrolizumab in a Phase II clinical trial. Symptoms reported as most severe over the course of the treatment over 9 weeks were fatigue [mean (M) = 3.8, SD = 2.3], pain (M = 3.7, SD = 2.9), disturbed sleep (M = 2.7, SD = 2.3), drowsiness (M = 2.6, SD = 2.0) and lack of appetite (M = 2.5, SD = 2.1). Pain in the abdomen (M = 2.2, SD = 2.4), rash (M = 1.1, SD = 1.8) and diarrhea (M = 0.9, SD = 1.5) were less severe. Interference with walking was rated the highest (M = 3.4, SD = 2.8) and relations with others was rated the lowest (M = 2.1, SD = 2.6). Using a composite score based on the five most severe symptoms (fatigue, pain, lack of appetite, feeling drowsy and sleep disturbance), 43% were classified into the high symptom burden group. Using a score based on immunotherapy-specific symptoms (e.g., rash, diarrhea) 33% of patients were included in the high symptom group. Symptom burden stayed relatively stable in the high- and low-symptom burden patient groups from baseline through 9 weeks. Some patients with rare malignancies experienced high symptom burden even at baseline. In patients with rare cancers, symptom trajectories stayed relatively stable over nine weeks of treatment with pembrolizumab.Trial registration: ClinicalTrials.gov identifier: NCT02721732.

Evaluating the psychometric properties of the Immunotherapy module of the MD Anderson Symptom Inventory.

INTRODUCTION: Immunotherapies have revolutionized the treatment of various cancers, but little is known about their symptomatic toxicity. Assessing these symptoms is best accomplished by asking the patients themselves. However, such reports are subjective and may face challenges as bonafide scientific data. Demonstrating the validity of symptom assessment tools, mainly through the reduction of measurement errors, has the potential to improve patient care if these tools are widely adopted. To that end, we present herein the psychometric properties of the Immunotherapy for Early-Phase Trials module of the MD Anderson Symptom Inventory (MDASI-Immunotherapy EPT) in patients receiving various immunotherapies in early phase trials at a major cancer center. METHODS: One hundred forty-five patients completed the inventory at baseline, with 85 of them also doing so after 9 weeks of treatment. The mean (±SD) age of the patients was 57.0±12.9 years. Also, 56% of the patients were women, 79% identified as white, and 49% had at least some college education. RESULTS: The internal consistency reliability of the MDASI-Immunotherapy EPT was excellent, as the Cronbach's alphas for all of its subscales were at least 0.88 (range 0.88-0.95). Known-group validity based on Eastern Cooperative Oncology Group performance status groupings was excellent at 9 weeks after the start of an immunotherapy trial for the MDASI-Immunotherapy EPT severity (effect size, 0.96) and interference (effect size, 0.82) subscales. We found substantial changes in the symptom items difficulty remembering (effect size, -0.85), fever and/or chills (effect size, -0.63), disturbed sleep (effect size, -0.52), diarrhea (effect size, -0.42), and swelling of hands, legs, or feet (effect size, -0.39). CONCLUSIONS: In conclusion, the MDASI-Immunotherapy EPT is a valid, reliable, and sensitive tool for measuring symptomatic toxicity.

Decrease in tumor content assessed in biopsies is associated with improved treatment outcome response to pembrolizumab in patients with rare tumors.

BACKGROUND: Decreased tumor content (TC) in resection specimens after neoadjuvant therapy is used to predict prognosis. We investigated whether TC assessed in biopsy specimens or the shift in TC from baseline to on-treatment can be used accordingly to predict response in patients with rare tumors who were treated with pembrolizumab. METHODS: A total of 57 tumors (represented by 173 baseline and 179 on-treatment biopsies) from 57 patients with rare tumors participating in an ongoing phase II clinical trial of pembrolizumab were evaluated. TC was estimated on H&E-stained slides and tumors were dichotomized into low and high TC according to a cut-off of 10%. Necrosis, proliferative fibrosis (PF) and normal tissue were assessed in on-treatment biopsies. TC at baseline and on-treatment, as well as the shift in TC from baseline to on-treatment, was correlated with clinical response defined according to Response Evaluation Criteria in Solid Tumors. RESULTS: A decrease in TC was seen in 14% (n=8); no change in TC was seen in 75% (n=43); and an increase in TC from baseline to on-treatment was seen in 11% (n=6). Objective response was significantly associated with decrease in TC from baseline to on-treatment (38%, 3/8) compared with no change/increase in TC (6%, 3/49) (p=0.031). Patients with a decrease in TC had a significantly increased time to progression (TTP) (75% probability) compared with patients with an increase (20% probability) or no change in TC (19% probability) (p=0.0042). Low TC was seen in 23% (13/57) of the tumors at baseline and in 26% (15/57) on-treatment. High TC was seen in 77% (44/57) of tumors at baseline and in 74% (42/57) on-treatment. No significant associations with response were seen for necrosis, PF or normal tissue in on-treatment biopsies. CONCLUSION: Patients with a decrease in TC from baseline to on-treatment had a significant improvement in objective response and a longer TTP. Our data suggest that the shift in TC might be used to predict response to pembrolizumab in rare tumors. However, further investigations in larger cohorts are needed to determine the clinical value of TC, the shift in TC and the cut-off of 10% assessed in biopsies. TRIAL REGISTRATION NUMBER: NCT02721732.

Effect of age and race on quality of life in young breast cancer survivors.

BACKGROUND: Given their early age at diagnosis, young breast cancer survivors (YBCSs) face issues that differ widely from their older counterparts. PATIENTS AND METHODS: We mailed a survey to 2209 patients who were ≤ 45 years at the time of breast cancer (BC) diagnosis. Each survey was composed of the Quality of Life in Adult Cancer Survivors instrument, Menopause Symptom Scale, and questions aimed at obtaining pertinent background information. RESULTS: One thousand ninety patients completed the survey. Mean age at time of diagnosis was 39.5 years; median years from diagnosis was 6.6 years. Distress related to vaginal dryness (P = .0002) and pain from intercourse (P = .0014) was significantly higher in patients who were < 5 years from diagnosis compared with those > 10 years from diagnosis. In the area of financial problems, black women had greater distress than did white women (P = .0010). Compared with white women, Hispanic women had worse family distress scores (P = .0028) and summary cancer-specific scores (P = .0076). Patients > 10 years from diagnosis had less sexual interest (P = .003) than did women who were closer to diagnosis. Women ≥ 40 years at diagnosis had significantly lower sexual interest (P = .0016) than did women < 40 years. Stage and neoadjuvant chemotherapy did not have a significant effect on quality of life (QOL). CONCLUSION: Even in comparison to stage and neoadjuvant chemotherapy, race, age at diagnosis, and time from diagnosis have significant long-term effects on QOL after treatment for BC.