Older clients with sophisticated or metastatic soft-tissue sarcoma (STS) had similar progression-free survival (PFS) whether they at first received basic chemotherapy or the angiogenesis inhibitor pazopanib (Votrient), which was much better endured, a randomized trial revealed.
Clients designated to doxorubicin had a typical PFS of 5.3 months as compared to 4.4 months with pazopanib. The outcome led to a risk ratio of 1.00, and the PFS values had overlapping self-confidence periods (CI). Goal reaction rate (ORR) and total survival (OS) likewise did not vary significantly between the two treatment groups.
Extreme neutropenia and febrile neutropenia, key secondary endpoints, occurred less typically with pazopanib, although general toxicity was comparable between the treatments, reported Viktor Grünwald, MD, PhD, of University Healthcare Facility Essen in Germany, and coworkers in the Journal of Clinical Oncology
” To accommodate the rarity of the subgroup of elderly clients with STS, a relaxed noninferiority margin (risk ratio) of 1.8 was used,” the authors kept in mind.
” Total occurrence of toxicity remained comparable for both treatment types, but there were distinctions in the AE [adverse event] profiles that might help assist the option of treatment for elderly patients,” they continued. “Our existing trial treatment primarily selects healthy elderly clients to participate in our trials. Future studies should concentrate on frail clients determined by GA [geriatric assessment] to assist establish a restorative technique for this susceptible client population.”
Long-Time Chemo Requirement
Doxorubicin has represented standard-of-care systemic therapy for innovative or metastatic STS since the 1970 s, even though the drug has well-recognized toxicity. In one research study including clients ages ≤65, doxorubicin triggered grade 4 neutropenia in a third of the clients and febrile neutropenia in 9%. Geriatric clients often require hospitalization as a result of doxorubicin-associated toxicity, Grünwald and colleagues kept in mind.
Pazopanib, which targets vascular endothelial growth element, produces minimal hematologic toxicity and has an international health status equivalent to placebo, the authors continued. The drug’s absence of extreme hematologic toxicity supplied the basis for a randomized trial to identify whether pazopanib is noninferior to doxorubicin as first-line therapy for older clients with advanced/metastatic STS.
Investigators in the German Sarcoma Working Group enrolled clients ages ≥60 with previously unattended chemotherapy-sensitive types of STS: fibrosarcoma, pleomorphic state-of-the-art sarcoma, leiomyosarcoma, liposarcoma, alveolar or pleomorphic rhabdomyosarcoma, vascular sarcoma, synovial sarcoma not otherwise defined, and malignant peripheral nerve sheath growths.
Patients were randomized 2:1 to everyday pazopanib or to doxorubicin q3w for a maximum of six cycles. The primary endpoint was PFS and noninferiority was defined by CIs with an upper limit of 1.8.
Tolerability, Efficacy Data
Information analysis included 120 clients, who had a typical age of71 A fourth of clients in each group had dosage decreases. In the subgroup of clients older than age 71, 13 (271%) randomized to pazopanib and six (40%) to doxorubicin had dosage reductions.
About a third of clients in each group discontinued treatment, consisting of 17 (354%) in the pazopanib arm and 6 (400%) in the doxorubicin arm who were older than age71 The rates of discontinuation for toxicity were 22%with pazopanib and 7.7%with doxorubicin.
The entire study population had a mean PFS of 4.4 months. The 0.9-month difference between the pazopanib and doxorubicin groups did not achieve statistical significance, and the CIs did not surpass the ceiling of the noninferiority margin (95%CI 0.65 -1.53). PFS rates at 12 and 26 weeks did not differ substantially in between the groups.
No patient in the pazopanib arm established grade 4 neutropenia versus 56.4%of clients in the doxorubicin arm ( P< 0. ORR was 12.3%with pazopanib and 15.4%with doxorubicin.
Security and tolerability information revealed unique AE profiles for pazopanib and doxorubicin. AEs, despite origin, and treatment-related AEs happened in a comparable percentage of clients in each treatment arm. The most common AEs (≥10%of patients) related to pazopanib were diarrhea, hypertension, hypothyroidism, and basic physical health deterioration. In contrast, the most typical AEs in the doxorubicin arm were alopecia, neutropenia, stomatitis, anemia, leukopenia, and mucosal swelling.
The authors mentioned that tolerability parameters beyond neutropenia might help determine the very best treatment option for an offered patient in the clinic setting. Furthermore, comorbidities and client preference “need to be aligned with characteristic AEs of a provided therapy.”
Offered data recommend a specific group of clients for which pazopanib is proper, said Brian A. van Branch, MD, of Washington University in St. Louis, who participated in a current trial of dose-escalated pazopanib in older patients with STS and ineligible for chemotherapy.
” For crippled older clients who want treatment, you can find out how well they do on therapy by starting them on pazopanib,” he informed MedPage Today “In our study, we did dose escalation of pazopanib and discovered that it was much better tolerated. I think that doxorubicin versus pazopanib as front-line therapy doesn’t matter so much as the clients who are being treated. The older clients get, the most likely I am to not wish to utilize doxorubicin.”
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< img alt="author['full_name']" src="https://clf1.medpagetoday.com/media/images/author/charlesBankhead_188 jpg" >Charles Bankheadis senior editor for oncology and likewise covers urology, dermatology, and ophthalmology. He signed up with MedPage Today in2007 Follow
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Disclosures
The study was supported by GlaxoSmithKline and Novartis.
Grünwald revealed pertinent relationships with Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Pfizer, Novartis, Ipsen, Eisai, Bayer, Merck Serono, Roche, Eli Lilly, PharmaMar, EUSA Pharma, Janssen-Cilag, Asklepios Kliniken, Diakonie Clinic, Dortmund Medical Facility, Klinikum Oldenburg, Onkowissen, and COR2ED.
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