Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma
Autor: | Van Cutsem, Eric, Tempero, Margaret A, Sigal, Darren, Oh, Do-Youn, Fazio, Nicola, Macarulla, Teresa, Hitre, Erika, Hammel, Pascal, Hendifar, Andrew E, Bates, Susan E, Li, Chung-Pin, Hingorani, Sunil R, de la Fouchardiere, Christelle, Kasi, Anup, Heinemann, Volker, Maraveyas, Anthony, Bahary, Nathan, Layos, Laura, Sahai, Vaibhav, Zheng, Lei, Lacy, Jill, Park, Joon Oh, Portales, Fabienne, Oberstein, Paul, Wu, Wilson, Chondros, Dimitrios, Bullock, Andrea J, HALO 109-301 Investigators |
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Rok vydání: | 2020 |
Předmět: |
Male
Spasm Paclitaxel Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Hyaluronoglucosaminidase Deoxycytidine Pancreatic Cancer Rare Diseases Double-Blind Method Clinical Research Albumins Antineoplastic Combined Chemotherapy Protocols Humans Oncology & Carcinogenesis Hyaluronic Acid Fatigue Response Evaluation Criteria in Solid Tumors Aged Cancer Carcinoma Evaluation of treatments and therapeutic interventions HALO 109-301 Investigators Middle Aged Progression-Free Survival Pancreatic Neoplasms Survival Rate Pancreatic Ductal 6.1 Pharmaceuticals Disease Progression Female Digestive Diseases Hyponatremia |
Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 38, iss 27 |
Popis: | PurposeTo evaluate the efficacy and safety of pegvorhyaluronidase alfa (PEGPH20) plus nab-paclitaxel/gemcitabine (AG) in patients with hyaluronan-high metastatic pancreatic ductal adenocarcinoma (PDA).Patients and methodsHALO 109-301 was a phase III, randomized, double-blind, placebo-controlled study. Patients ≥ 18 years of age with untreated, metastatic, hyaluronan-high PDA were randomly assigned 2:1 to PEGPH20 plus AG or placebo plus AG. Treatment was administered intravenously in 4-week cycles (3 weeks on, 1 week off) until progression or intolerable adverse events: PEGPH20 3.0 µg/kg twice per week for cycle 1 and once per week thereafter; nab-paclitaxel 125 mg/m2 once per week; and gemcitabine 1,000 mg/m2 once per week. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Response was independently assessed per RECIST v1.1.ResultsAt data cutoff, 494 patients were randomly assigned, with 492 (327 for PEGPH20 and 165 for placebo) included in intention-to-treat analyses. Baseline characteristics were balanced for PEGPH20 plus AG versus placebo plus AG. There were 330 deaths, with a median OS of 11.2 months for PEGPH20 plus AG versus 11.5 months for placebo plus AG (hazard ratio [HR], 1.00; 95% CI, 0.80 to 1.27; P = .97); median PFS was 7.1 months versus 7.1 months (HR, 0.97 [95% CI, 0.75 to 1.26]); ORR was 47% versus 36% (ORR ratio, 1.29 [95% CI, 1.03 to 1.63]). Grade ≥ 3 adverse events with a ≥ 2% higher rate with PEGPH20 plus AG than with placebo plus AG included fatigue (16.0% v 9.6%), muscle spasms (6.5% v 0.6%), and hyponatremia (8.0% v 3.8%).ConclusionThe addition of PEGPH20 to AG increased the ORR but did not improve OS or PFS. The safety profile of PEGPH20 plus AG was consistent with that found in previous studies. These results do not support additional development of PEGPH20 in metastatic PDA. |
Databáze: | OpenAIRE |
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