Immune System-Activating Drugs in Combination Treatments May Be Next Big Thing for Melanoma

Among solid tumors, the curative potential of immunotherapies has been explored most in melanoma. One reason for this is that melanoma tumors often contain so-called immune infiltrates—patches of T cells, the killer cells of the immune system. It seems that these fighter cells arrive at the ‘battlefield’ to target tumor cells for killing, but instead become ‘frozen,’ unable to attack.  How to activate the tumor-killing potential of T cells has been an area of intense and fruitful research, leading to the development of several immunotherapy drugs. Continue reading…

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

“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.”