Vanesa Gregorc, MD
The phase III NGR015 trial reported in The Lancet Oncology by Vanesa Gregorc, MD, of Ospedale San Raffaele, Milan, and colleagues found no benefit of adding NGR-hTNF to best investigator choice of treatment in patients with previously treated malignant pleural mesothelioma.
NGR-hTNF consists of human TNFα conjugated to the tumor-targeting peptide NGR. The agent acts as a vascular-targeting drug that increases the penetration of intratumoral chemotherapy and T-cell infiltration via modification of the tumor microenvironment.
In the double-blind trial, 400 patients from 41 sites in 12 countries with disease progressing on or after pemetrexed (Alimta)-based first-line therapy were randomly assigned to receive weekly intravenous NGR-hTNF at 0.8 μg/m2 plus best investigator choice of treatment (n = 200) or placebo plus best investigator choice (n = 200). Best investigator choice was decided before random assignment and could be single-agent gemcitabine at 1,000 to 1,250 mg/m2, vinorelbine at 25 mg/m2 intravenously or 60 mg/m2 orally, doxorubicin at 60 to75 mg/m2, or best supportive care. Overall, 381 patients received chemotherapy as best choice.
The primary endpoint was overall survival in the intention-to-treat population.
Survival Outcomes and Adverse Events
At the cutoff date in April 2014, the median follow-up was 18.7 months. The median overall survival was 8.5 months in the NGR-hTNF group vs 8.0 months in the placebo group (hazard ratio [HR] = 0.94, P = .58). No difference was observed between the gemcitabine subgroups or vinorelbine subgroups in the NGR-hTNF vs placebo groups.
The median progression-free survival was 3.4 vs 3.0 months (HR = 0.95, P =.65). Among patients with a shorter treatment-free interval (less than the population median of 4.8 months) before study treatment, the median progression free survival was 3.4 vs 1.9 months (HR = 0.67, P = .0065).
Grade ≥ 3 adverse events occurred in 70% of the NGR-hTNF group vs 61% of the placebo group, with the most common being neutropenia (18% vs 19%), pain (6% vs 8%), dyspnea (5% vs 4%), and chills (5% vs 0%). Serious adverse events occurred in 26% vs 24% of patients and were considered treatment-related in 9% vs 10%. There were 12 deaths in the NGR-hTNF group and 13 deaths in the placebo group during study treatment, with none considered related to treatment.
The investigators concluded, “The study did not meet its primary endpoint. The hypothesis-generating findings from the subgroup analyses deserve a confirmatory randomised trial because patients who rapidly progress after first-line treatment have a poor prognosis.” ■