U.S. Food and Drug Administration Approval: Peginterferon-alfa-2b for the Adjuvant Treatment of Patients with Melanoma

Herndon, Thomas M.; Demko, Suzanne; Jiang, Xiaoping; He, Kun; Gootenberg, Joseph E.; Cohen, Martin H.; Keegan, Patricia; Pazdur, Richard

doi:10.1634/theoncologist.2012-0123

Cited by 77 publications

(54 citation statements)

References 14 publications

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“…[13,14] Recently, pegylated IFN α-2b was approved for use in adult patients with high-risk melanoma based on the results of the European Organisation for Research and Treatment of Cancer (EORTC) 18991 trial in which significant improvement in disease-free survival (DFS) was observed in patients with resected stage III melanoma. [15] The adverse events in adults appear to be similar to nonpegylated IFN α-2b. [16,17] Based on the potential benefit observed with pegylated IFN α-2b in adult patients with melanoma and the more convenient once weekly dosing, we conducted a study to determine the feasibility and safety of pegylated IFN α-2b once weekly as a subcutaneous injection following an initial induction phase of highdose IFN α-2b in children and adolescents with resected 2002 American Joint Committee on Cancer (AJCC) [18] Stage IIC, IIIA, or IIIB cutaneous melanoma.…”

Section: Introductionmentioning

confidence: 94%

“…Preclinical and clinical studies indicate that the biological activity of IFN α‐2b is similar, if not better than conventional IFN . Recently, pegylated IFN α‐2b was approved for use in adult patients with high‐risk melanoma based on the results of the European Organisation for Research and Treatment of Cancer (EORTC) 18991 trial in which significant improvement in disease‐free survival (DFS) was observed in patients with resected stage III melanoma . The adverse events in adults appear to be similar to nonpegylated IFN α‐2b …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Feasibility of Pegylated Interferon in Children and Young Adults With Resected High‐Risk Melanoma

Navid

Herzog

Sandoval

et al. 2016

Pediatric Blood & Cancer

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Background Pegylated interferon α-2b (IFN α-2b) improves disease-free survival in adults with resected stage III melanoma. We conducted a study to determine the feasibility and safety of incorporating pegylated IFN α-2b as adjuvant therapy in the treatment of children and adolescents with high-risk melanoma. Pharmacokinetic studies of IFN α-2b and neuropsychological and quality of life (QOL) assessments were performed. Patient and Methods Eligible patients with resected AJCC Stage IIC, IIIA and IIIB cutaneous melanoma received non-pegylated IFN α-2b 20 million units/m2/day intravenously 5 days per week for 4 weeks (induction) followed by pegylated IFN α-2b 1 mcg/kg/dose weekly subcutaneously (SQ) for 48 weeks (maintenance). Results Twenty-three patients (15 females, median age 10 years) were enrolled. All patients completed induction therapy; whereas, 5 patients did not complete maintenance therapy either because of recurrent disease (n=2) or toxicity (n=3). The most common grade 3-4 toxicities of pegylated IFN α-2b were neutropenia (35%) and elevated liver transaminases (17%). The median non-pegylated IFN α-2b AUC0-∞ (5,026 pcg*hr/mL) was similar to adults. The median pegylated IFN α-2b exposure (48,480 pcg*hr/mL) was greater than the cumulative weekly exposure for non-pegylated IFN α-2b administered SQ three times per week (TIW). Validated measures demonstrated an improvement in QOL scores and no decline in psychological functioning over the course of therapy. Conclusions Pegylated IFN α-2b 1 mcg/kg/dose SQ weekly as maintenance therapy in children and adolescents with high-risk melanoma is feasible with tolerable toxicity and appears to yield higher exposures than non-pegylated IFN α-2b administered SQ TIW.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Feasibility of Pegylated Interferon in Children and Young Adults With Resected High‐Risk Melanoma

Navid

Herzog

Sandoval

et al. 2016

Pediatric Blood & Cancer

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“…Based on this study result, IFN‐α‐2b has been utilized as a global standard for adjuvant therapy in patients with high‐risk malignant melanoma . Recently, pegylated (PEG) IFN‐α‐2b became available in several countries including the USA and made treatments easier …”

Section: Introductionmentioning

confidence: 99%

“…3,4 Recently, pegylated (PEG) IFN-a-2b became available in several countries including the USA and made treatments easier. 5 Pegylated IFN-a-2b in patients with stage III malignant melanoma who have undergone surgery demonstrated statistically meaningful extension of recurrence-free survival (RFS) in a large phase III (European Organization for Research and Treatment of Cancer [EORTC] 18991) study when administrated at 6 lg/kg per week (8 weeks) in the induction phase and 3 lg/ kg per week (up to 5 years in total) in the maintenance phase. 6 ECOG 1684 and EORTC 18991 were randomized, multinational, comparative studies with confirmed efficacies; however, in Japan, both IFN-a-2b and PEG IFN-a-2b remained unapproved for adjuvant treatment of malignant melanoma after surgery.…”

Section: Introductionmentioning

confidence: 99%

Phase I study of pegylated interferon‐alpha‐2b as an adjuvant therapy in Japanese patients with malignant melanoma

Yamazaki¹,

Uhara

Wada

et al. 2016

The Journal of Dermatology

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In the adjuvant setting for malignant melanoma, interferon (IFN)‐α‐2b and pegylated (PEG) IFN‐α‐2b were approved in several countries including the USA before these were approved in Japan. To resolve the “drug‐lag” issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN‐α‐2b. As with a previously reported phase III study, patients were to receive PEG IFN‐α‐2b 6 μg/kg per week s.c. during an 8‐week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose‐limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose‐limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug‐related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration–time curve and maximum observed serum concentration were observed between Japanese and historical non‐Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN‐α‐2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial.

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“…Furthermore, early clinical studies in vascular tumors, such as infantile hemangioma, giant cell tumor of the mandible, and renal carcinoma, support the selection and monitoring of IFN therapy in relation to elevated plasma or urine FGF concentrations (12–14). Recently, a longer-acting formulation of interferon, peginterferon α-2b (Peg-IFN), was approved by the U.S. Food and Drug Administration for the adjuvant treatment of patients with melanoma at a dose of 6 μg/kg (induction for 8 weeks), then 3 μg/kg (maintenance up to 5 years) injected subcutaneously once a week based on a phase III trial (15, 16). …”

Section: Introductionmentioning

confidence: 99%

ECOG Phase II Trial of Graded-Dose Peginterferon α-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602)

Lee

Shin

et al. 2013

Clinical Cancer Research

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Purpose We investigated use of graded-dose peginterferon α-2b (Peg-IFN) in patients with stage IV melanoma overexpressing basic fibroblast growth factor (FGF-2). The primary objective was suppression of plasma FGF-2 to within normal range (≤7.5 pg/mL). Experimental Design Plasma FGF-2 was measured at baseline (Step 1), and patients with concentrations ≥15 pg/mL were eligible for study treatment (Step 2). Peg-IFN was given weekly at starting dose of 0.5 μg/kg/wk with increment every 3 weeks based on serial FGF-2 concentrations. Results Two hundred seven patients entered Step 1; 45 (22%) overexpressed FGF-2 (median=22 pg/dL). Twenty-nine eligible patients entered Step 2 and received treatment. Patients’ median age was 64 years (range, 29–84 years). Most had >2 prior therapies. FGF-2 decreased in 28 (97%) patients, with suppression to normal range in 10 (35%). Median time to FGF-2 suppression was 30 days. The best clinical responses were partial response (7%) and stable disease (17%). Median progression-free survival (PFS) and overall survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely than those who did not to have a response or stable disease (P = 0.03). Vascular endothelial growth factor (VEGF) concentrations decreased in 27 patients (93%) during treatment and paralleled those of FGF-2 over time. We found no compensatory rise in VEGF among those with FGF-2 suppression. Conclusions Graded-dose Peg-IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2. Over a third of patients had complete suppression of plasma FGF-2, which correlated with clinical response to this therapy.

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U.S. Food and Drug Administration Approval: Peginterferon-alfa-2b for the Adjuvant Treatment of Patients with Melanoma

Cited by 77 publications

References 14 publications

Feasibility of Pegylated Interferon in Children and Young Adults With Resected High‐Risk Melanoma

Feasibility of Pegylated Interferon in Children and Young Adults With Resected High‐Risk Melanoma

Phase I study of pegylated interferon‐alpha‐2b as an adjuvant therapy in Japanese patients with malignant melanoma

ECOG Phase II Trial of Graded-Dose Peginterferon α-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602)

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