etirinotecan-pegol and Neoplasm-Metastasis

The increasing incidence of breast cancer brain metastases is a major clinical problem with its associated poor prognosis and limited treatment options. The long-acting topoisomerase-1 inhibitor, etirinotecan pegol, was designed to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Motivated by improved survival findings from subgroup analyses from the Phase III BEACON trial, this ongoing randomized, Phase III trial compares etirinotecan pegol to drugs commonly used for advanced breast cancer in patients with stable, treated breast cancer brain metastases who have been previously treated with an anthracycline, taxane and capecitabine. The primary end point is overall survival. Secondary end points include objective response rate, progression-free survival and time to CNS disease progression or recurrence in patients with/without CNS lesions present at study entry. Trial registration number: NCT02915744.

Topics: Adult; Aged; Brain Neoplasms; Breast Neoplasms; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Polyethylene Glycols; Progression-Free Survival; Topoisomerase I Inhibitors

Third-line treatment options are limited for patients with metastatic non-small-cell lung cancer (NSCLC). Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor. We conducted a single-arm phase II trial to evaluate its efficacy in third-line treatment.. Patients aged ≥ 18 years with histologically proven NSCLC who had received 2 previous systemic therapy regimens, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and adequate end-organ function were eligible. Etirinotecan pegol was administered at a dose of 145 mg/m. From January 2013 to January 2015, 40 patients were enrolled. Their median age was 66 years (range, 19-85 years), 45% were female, 30% had an ECOG performance status of 0, 96% were current and former smokers, and 31 had adenocarcinoma. Patients received a median of 3 cycles (range, 2-15) of protocol therapy. The best response was a partial response in 2 patients. The treatment was well tolerated; 3 patients had grade 3 gastrointestinal toxicity attributable to therapy. The median PFS was 2.3 months (95% confidence interval [CI], 1.3-4.4 months), and the median OS was 7.1 months (95% CI 4.2-11.4 months).. Etirinotecan pegol was well tolerated and led to 2 partial responses and disease stabilization with this third-line treatment of metastatic NSCLC. However, the study failed to meet its prespecified response rate endpoint.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Diseases; Heterocyclic Compounds, 4 or More Rings; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Polyethylene Glycols; Survival Analysis; Topoisomerase I Inhibitors; Treatment Outcome; Young Adult

Topics: Antineoplastic Agents; Breast; Breast Neoplasms; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Microtubules; Molecular Targeted Therapy; Neoplasm Metastasis; Polyethylene Glycols; Receptor, ErbB-2