A phase II study of pazopanib as front-line therapy in patients with non-resectable or metastatic soft-tissue sarcomas who are not candidates for chemotherapy.

BACKGROUND: Cytotoxic chemotherapy remains the standard of care first-line treatment for advanced and metastatic soft-tissue sarcomas (STSs). Certain patients may not be chemotherapy candidates based upon age or co-morbidities, leaving limited treatment options. Pazopanib is a multi-targeted tyrosine kinase inhibitor that is FDA-approved for metastatic STS after the first line. We proposed a phase II study evaluating pazopanib as a first-line agent in patients with advanced disease who are deemed not to be candidates for chemotherapy. METHODS: Eligible patients were at least 18 years old, not candidates for chemotherapyand were treatment naive. Pazopanib was titrated from 200 mg twice daily to a goal of 800 mg daily. The primary end point was the clinical benefit rate (CBR) (CBR = completed response + partial response + stable disease per Response Evaluation Criteria in Solid Tumours [RECIST 1.1]) at 16 weeks. The sample size of 56 evaluable patients was calculated to provide 80% power to test a hypothesised CBR of ≥35% against an unfavourable CBR of ≤20%. If ≥ 17 patients achieved benefit, the null CBR of 20% would be rejected at a nominal 5% alpha level. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life and serum biomarkers. FINDINGS: Fifty-six patients were enrolled from May 2015 to February 2019 and are included in the intention-to-treat analysis. Median PFS was 3.67 (2.62-7.25) months. Median OS was 14.16 (95% confidence interval [CI]: 8.4-NR) months, CBR = 39.29% (22/56) (CI = 0.265-0.533, p = 0.0007). No new or unexpected adverse events were seen. The most common grade I-II events were diarrhoea, nausea and fatigue. The most common grade III-IV events were hypertension and liver function test abnormalities. INTERPRETATION: These data suggest that there is a benefit to front-line pazopanib in patients with STS who are not candidates for cytotoxic chemotherapy.

Accuracy of perceived risk of recurrence among patients with early-stage breast cancer.

BACKGROUND: Accurate breast cancer recurrence risk perceptions might motivate health-promoting behaviors and alleviate undue anxiety. Although a few studies have examined early-stage breast cancer survivors' perceived risk of recurrence, none have assessed the accuracy of survivors' perceived risk of recurrence. METHODS: First primary ductal carcinoma in situ and early-invasive breast cancer survivors reported their perceived risk of recurrence during 6- and 12-month postsurgery interviews. We estimated the patients' 10-year risk of recurrence from published clinical trials, and for early-invasive breast cancer patients, risk of distant recurrence was based on their breast cancer-specific mortality calculated using Adjuvant! Online. Patients' perceived risk was compared with their calculated risk and categorized as "Accurate," "Underestimated," "Overestimated," and "Uncertain." Multinomial logit marginal effect models were fitted using Accurate as the reference. RESULTS: Only 17% of 531 patients accurately perceived their risk at 6 months, most of whom inaccurately perceived their risk at 12 months (P = 0.0143). Patients who were nonwhite [odds ratio (OR), 1.70; 95% confidence interval (95% CI), 1.12-2.56] and received radiation therapy (OR, 2.01; 95% CI, 1.07-3.77) were more likely to underestimate their risk. Patients with ductal carcinoma in situ (OR, 1.76; 95% CI, 1.11-2.79), [corrected] lower social support (OR, 0.71; 95% CI, 0.53-0.95), and anxiety (OR, 1.58; 95% CI, 1.01-2.47) were more likely to overestimate their risk. CONCLUSION: Few breast cancer survivors accurately perceived their risk of recurrence. IMPACT: The accuracy of perceived risk may be increased by better physician-patient communications about their prognosis, provision of social support, and treatment for coexisting anxiety.