KRAS mutations are present in 30% of lung adenocarcinomas. Salirasib prevents Ras membrane binding thereby blocking the function of all Ras isoforms. This phase II study determined the activity of salirasib in patients with advanced lung adenocarcinomas with KRAS mutations.
Methods
Two cohorts of patients with stage IIIB/IV lung adenocarcinoma were eligible: patients with tumors with KRAS mutations who were previously treated with chemotherapy and patients receiving initial therapy who had ≥15 pack-year smoking history. Salirasib was given orally from days 1 to 28 of a 35-day cycle. The primary end point was the rate of nonprogression at 10 weeks.
Results
Thirty-three patients were enrolled. Thirty patients had KRAS mutations (23 patients who were previously treated and 7/10 patients who had no prior therapy). Of the previously treated patients, 7 of 23 (30%) had stable disease at 10 weeks, and 4 of 10 (40%) previously untreated patients had stable disease at 10 weeks. No patient had a radiographic partial response (0% observed rate, 95% confidence interval 0–12%). The median overall survival was not reached (>9 months) for previously untreated patients and it was 15 months for patients who received prior chemotherapy. Diarrhea, nausea, and fatigue were the most common toxicities.
Conclusions
Salirasib at the current dose and schedule has insufficient activity in the treatment of KRAS mutant lung adenocarcinoma to warrant further evaluation. The successful enrollment of 30 patients with tumors with KRAS mutant lung adenocarcinoma over 15 months at a single site demonstrates that drug trials directed at a KRAS-specific genotype in lung cancer are feasible.
Key Words
Lung adenocarcinoma
Salirasib
KRAS
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Disclosure: Dr. Riely has been a compensated consultant for AstraZeneca, Boehringer-Ingelheim, Tragara, Ariad, and Chugai. This study was sponsored by Concordia Pharmaceuticals.
William Pao is currently at Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
Melissa L. Johnson is currently at Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.