Anti-NaPi2b antibody–drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study
| Autor: | Kedan Lin, B Mackowiak-Matejczyk, Erika Hamilton, Joyce F. Liu, Kathleen N. Moore, Daniel J. Maslyar, Amit M. Oza, Michael J. Birrer, Lemahieu, Peter Trask, YounJeong Choi, Eva Schuth, Susana Banerjee, Jurjees Hasan, Jim Marsters, Yulei Wang, Eric W. Humke, Alexandra Leary, J Pikiel, I.L. Ray-Coquard, Anjali Vaze |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty Antibody-drug conjugate Immunoconjugates Organoplatinum Compounds Population Phases of clinical research Antibodies Monoclonal Humanized Gastroenterology Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Humans Adverse effect education Survival analysis Aged Aged 80 and over Ovarian Neoplasms education.field_of_study Antibiotics Antineoplastic business.industry Hazard ratio Hematology Middle Aged Survival Analysis 030104 developmental biology Oncology Monomethyl auristatin E chemistry Doxorubicin Drug Resistance Neoplasm 030220 oncology & carcinogenesis Monoclonal Female business Biomarkers |
| Zdroj: | Annals of Oncology. 29:917-923 |
| ISSN: | 0923-7534 |
| Popis: | Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m(2), intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade >= 3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade >= 2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC. |
| Databáze: | OpenAIRE |
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