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

We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. 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 endpo...

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Veröffentlicht in:	Clinical cancer research Jg. 23; H. 19; S. 5711
Hauptverfasser:	Gray, Jhanelle E, Heist, Rebecca S, Starodub, Alexander N, Camidge, D Ross, Kio, Ebenezer A, Masters, Gregory A, Purcell, W Thomas, Guarino, Michael J, Misleh, Jamal, Schneider, Charles J, Schneider, Bryan J, Ocean, Allyson, Johnson, Tirrell, Gandhi, Leena, Kalinsky, Kevin, Scheff, Ronald, Messersmith, Wells A, Govindan, Serengulam V, Maliakal, Pius P, Mudenda, Boyd, Wegener, William A, Sharkey, Robert M, Goldenberg, David M
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.10.2017
Schlagworte:	Adult Aged Aged, 80 and over Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - adverse effects Antigens, Neoplasm - immunology Camptothecin - administration & dosage Camptothecin - adverse effects Camptothecin - analogs & derivatives Camptothecin - immunology Cell Adhesion Molecules - antagonists & inhibitors Cell Adhesion Molecules - immunology Disease-Free Survival DNA Topoisomerases, Type I - genetics DNA Topoisomerases, Type I - immunology Drug-Related Side Effects and Adverse Reactions - classification Drug-Related Side Effects and Adverse Reactions - pathology Female Humans Immunoconjugates - administration & dosage Immunoconjugates - adverse effects Immunoconjugates - chemistry Kaplan-Meier Estimate Male Middle Aged Molecular Targeted Therapy Small Cell Lung Carcinoma - drug therapy Small Cell Lung Carcinoma - immunology Small Cell Lung Carcinoma - pathology Topoisomerase I Inhibitors - administration & dosage Topoisomerase I Inhibitors - adverse effects
ISSN:	1078-0432, 1557-3265, 1557-3265
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Zusammenfassung:	We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. 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. Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis ( = 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. 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. .
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265 1557-3265
DOI:	10.1158/1078-0432.CCR-17-0933