Nelfinavir Plus Concurrent Chemoradiotherapy Shows Promise in Locally Advanced NSCLC
In a clinical trial of patients with locally advanced non–small-cell lung cancer (NSCLC), nelfinavir administered with concurrent chemoradiotherapy was well-tolerated and showed promising long-term local control and survival (JAMA Oncol. 2019 Aug 22. Epub ahead of print).
Among patients with locally advanced NSCLC, local failure following chemoradiotherapy significantly contributes to mortality. Ramesh Rengan, MD, PhD, Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, and colleagues suggested that one way to improve local control would be through targeted radiosensitization of the tumor.
Thus, Dr Rengan et al conducted a prospective, open-label, single-group, phase 1/2 study assessing the dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose of nelfinavir mesylate, administered concurrently with chemoradiotherapy in patients with locally advanced NSCLC. The purpose of the phase 2 branch of the study was to estimate the objective response rate, local and distant failure rates, and overall survival (OS).
A total of 35 patients (aged 18-89 years) with unresectable, stage IIIA/IIIB locally advanced NSCLC were enrolled in the study between June 29, 2007, and February 22, 2012, and given nelfinavir 625 mg (n = 5) or 1250 mg (n = 30) twice daily for 7 to 14 days before and during receipt of concurrent chemoradiotherapy. Follow-up lasted for a median of 6.8 years, and data were analyzed on May 9, 2017.
The results yielded no dose-limiting toxicities or grade ≥4 nonhematologic toxic effects. There were 33 patients with evaluable posttreatment CT scans, with an objective response rate of 94% (31 of 33; 95% CI, 86%-100%).
According to Dr Rengan and his co-investigators, the cumulative incidence of local failure was 39% (95% CI, 30.5%-47.5%), and the median progression-free survival rate was 11.7 months (95% CI, 6.2-17.1 months). In addition, across all patients, the median OS was 41.1 months (95% CI, 19.0-63.1 months), and the 5-year mean OS was 37.1%.
“This study suggests that nelfinavir administered with concurrent CT-RT [chemoradiotherapy] is associated with acceptable toxic effects and a promising objective response rate, local failure, progression-free survival, and overall survival in unresectable LA-NSCLC,” Dr Rengan and colleagues said.
“These data suggest that nelfinavir may enhance the efficacy of standard CT-RT [chemoradiotherapy] in this disease. Additional testing in the randomized phase 3 setting should be conducted to establish the improvement associated with nelfinavir with concurrent CT-RT [chemoradiotherapy],” they concluded.—Hina Porcelli