A novel antibody-drug conjugate is well tolerated and induces durable responses in pretreated patients with advanced non-small cell lung cancer (NSCLC), according to research published in the Journal of Clinical Oncology (published online May 26, 2017; doi:10.1200/JCO.2016.72.1894).
Only a fraction of patients with metastatic NSCLC respond to currently approved first-line therapies. A critical need remains for further therapeutic options for patients who do not respond to therapy or progress on given therapy. Sacituzumab govitecan is a novel antibody-drug conjugate that targets Trop-2 – a 46-kD glycoprotein overexpressed in many epithelial cancers and a potential target for NSCLC treatment.
Rebecca Suk Heist, MD, MPH, Massachusetts General Hospital (Boston, MA), and colleagues conducted a single-arm multicenter trial to assess sacituzumab govitecan response in patients with pretreated metastatic NSCLC. A total of 54 patients (47 of whom were response-assessable) received either 8 or 10 mg/kg of the antibody-drug conjugate on days 1 and 8 of 21-day cycles. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS).
Results of the analysis showed an ORR of 19%, a median response duration of 6.0 months (95% CI, 4.8-8.3), and a clinical benefit rate—which included composite measurement of complete response, partial response, and stable disease of 4 months or longer—of 43% among all patients. In the intention-to-treat population, ORR was 17% (9 of 54 patients). Median PFS in this population was 5.2 months (95% CI, 3.2-7.1 months) and median OS was 9.5 months (95% CI, 5.9-16.7 months).
Grade 3 or higher adverse events associated with sacituzumab govitecan included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%).
Authors of the study acknowledged that more than 90% of 26 assessable archival tumor specimens were observed to be highly positive for Trop-2 by immunohistochemistry, which indicates that Trop-2 cannot be considered a predictive biomarker for response.
Findings of the study suggest that sacituzumab govitecan is well-tolerated and induces durable responses in heavily pretreated patients with advanced, metastatic NSCLC.
“This ADC should be studied further in this disease and in other patients with Trop-2–expressing tumors,” the authors wrote, indicating a need for further study.—Zachary Bessette