Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors
| Autor: | Rosa Nadal, Piyush K. Agarwal, Sumanta K. Pal, Biren Saraiya, Howard L. Parnes, Donald P. Bottaro, Daniel Girardi, Vladimir Valera, Mohammad Hadi Bagheri, Lisa Ley, Scot Anthony Niglio, Olena Sierra Ortiz, Seth M. Steinberg, Yangmin M. Ning, Primo N. Lara, William D. Figg, Paul Monk, Heather J. Chalfin, Mark N. Stein, Howard Streicher, Carlos Diaz, Marissa Mallek, Amir Mortazavi, Maria J. Merino, Jacqueline Cadena, Rene Costello, Min-Jung Lee, Jane B. Trepel, William L. Dahut, Nicole N. Davarpanah, James L. Gulley, Andrea B. Apolo, John J. Wright, Jennifer Jones, Lisa M. Cordes |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research Pyridines Gastroenterology B7-H1 Antigen Hepatitis chemistry.chemical_compound 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Medicine Anilides 030212 general & internal medicine Fatigue Aged 80 and over ORIGINAL REPORTS Middle Aged Proto-Oncogene Proteins c-met Colitis Epithelial Cell Adhesion Molecule Neoplastic Cells Circulating Progression-Free Survival Survival Rate Nivolumab Oncology Response Evaluation Criteria in Solid Tumors 030220 oncology & carcinogenesis Hypertension Female medicine.drug Adult Diarrhea Receptors CXCR4 medicine.medical_specialty Cabozantinib Ipilimumab Genitourinary Cancer Young Adult 03 medical and health sciences Internal medicine Carcinoma Humans Progression-free survival Adverse effect Survival rate Aged Carcinoma Transitional Cell business.industry medicine.disease chemistry business Urogenital Neoplasms |
| Zdroj: | Journal of Clinical Oncology |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.20.01652 |
| Popis: | PURPOSE We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations. |
| Databáze: | OpenAIRE |
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