pazopanib and Chest-Pain

Metastatic soft tissue sarcomas (STSs) management remains an unmet medical need. We assessed the activity and safety of regorafenib in patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib.. This double-blind, placebo-controlled, multicenter comparative randomized phase II trial included patients with histologically proven advanced and inoperable STS. Patients receiving placebo were offered optional cross-over for centrally confirmed disease progression. Primary end-point was centrally reviewed Response Evaluation Criteria in Solid Tumours-based progression-free survival (PFS), analysed on the intent-to-treat data set. In total, 24 events were required for 90% power, hazard ratio (HR) = 0.33 (median PFS, 3.6 versus 1.2 months), and 1-sided α = 0.1 (ClinicalTrials.gov, NCT01900743).. From December 2015 to October 2017, 37 patients were randomized; 18 to regorafenib and 19 to placebo. Thirteen patients assigned to placebo switched to regorafenib after progression. Median follow-up was 27.2 months (95% confidence interval [CI]: 24.4-not reached). We observed a significant PFS benefit of regorafenib compared with placebo (adjusted HR = 0.33; 95% CI: 0.15-0.74; p = 0.0007 median PFS = 2.1 versus 1.1 months, respectively), and a large and nearly significant overall survival (OS) benefit despite the cross-over (adjusted HR = 0.49; 95% CI: 0.23-1.06; p = 0.007; median OS = 17.8 versus 8.2 months). Before cross-over, the most common grade III or higher adverse events were lymphopenia (5 versus 1, respectively), diarrhoea (4 versus 0), dyspnoea (3 versus 1), skin toxicity (3 versus 0), arterial hypertension (2 versus 0), and increased transaminases (2 versus 0).. The present study demonstrated a meaningful clinical anti-tumour activity with regorafenib in heavily pre-treated patients with non-adipocytic STS.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chest Pain; Cross-Over Studies; Diarrhea; Disease Progression; Double-Blind Method; Female; Humans; Indazoles; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Phenylurea Compounds; Pyridines; Pyrimidines; Sarcoma; Soft Tissue Neoplasms; Sulfonamides; Treatment Outcome

A 42-year-old woman presented with chest pain and breathlessness with a nodule measuring 2×2 cm in size at the base of the right lung. A bronchoscopic examination did not reveal any malignancy. However, the patient developed difficulty in breathing, enlargement of the nodule, and right pleural effusion 14 days later. A video-assisted thoracic surgical biopsy specimen revealed the presence of pleural synovial sarcoma. The patient was treated with doxorubicin-ifosfamide combination chemotherapy because of metastasis to the pelvis. However, after a transient partial clinical response, there was a relapse of refractory disease. Although treated with pazopanib as second-line chemotherapy, the patient died eight months after the initial presentation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chest Pain; Doxorubicin; Dyspnea; Fatal Outcome; Female; Humans; Ifosfamide; Indazoles; Neoplasm Recurrence, Local; Pleural Effusion, Malignant; Pleural Neoplasms; Pyrimidines; Sarcoma, Synovial; Sulfonamides