Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I–inhibiting Antibody–Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan

Autor: Allyson J. Ocean, David M. Goldenberg, Pius Maliakal, Michael J. Guarino, William A. Wegener, Kevin Kalinsky, Alexander Starodub, D. Ross Camidge, Jamal Misleh, Wells A. Messersmith, Boyd Mudenda, Robert M. Sharkey, Jhanelle E. Gray, Ebenezer A. Kio, Leena Gandhi, Tirrell Johnson, Gregory A. Masters, Bryan J. Schneider, Rebecca S. Heist, Charles J. Schneider, Ronald J. Scheff, W. Thomas Purcell, Serengulam V. Govindan
Rok vydání: 2017
Předmět:
Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Immunoconjugates
Drug-Related Side Effects and Adverse Reactions
Combination therapy
medicine.medical_treatment
Population
Kaplan-Meier Estimate
Neutropenia
Antibodies
Monoclonal
Humanized
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Antigens
Neoplasm
Internal medicine
Humans
Medicine
Molecular Targeted Therapy
education
Adverse effect
Aged
Aged
80 and over
education.field_of_study
Chemotherapy
business.industry
Cancer
Middle Aged
medicine.disease
Small Cell Lung Carcinoma
Surgery
030104 developmental biology
DNA Topoisomerases
Type I
030220 oncology & carcinogenesis
Sacituzumab govitecan
Camptothecin
Female
Topotecan
Topoisomerase I Inhibitors
business
Cell Adhesion Molecules
medicine.drug
Zdroj: Clinical Cancer Research. 23:5711-5719
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-17-0933
Popis: Purpose: We evaluated a Trop-2–targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1–7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections. Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711–9. ©2017 AACR.
Databáze: OpenAIRE
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