CHICAGO—In a phase 1 study in advanced non–small-cell lung cancer (NSCLC) deemed worthy of a presentation at the American Society of Clinical Oncology’s 46th annual meeting plenary session, a multinational group of investigators reported improved survival with an oral investigational agent still unfamiliar to most oncologists.
Crizotinib (PF-1066), an inhibitor of anaplastic lymphoma kinase (ALK), targets a fusion protein called EML4/ALK, which drives tumor growth in 3% to 5% of all NSCLC patients. In the study presented, crizotinib produced tumor shrinkage in 57% and prolonged remission in 72% of heavily pretreated advanced NSCLC patients selected for the presence of the ALK protein.
“Our results were very impressive. The majority of patients responded, often within the first 2 weeks of treatment, and the responses were often durable,” reported Yung-Jue Bang, MD, PhD, of Seoul National University in South Korea.
The data come from an ongoing phase 1 first-in-human trial of patients with ALK-positive NSCLC treated with crizotinib after their tumors progressed, often after multiple treatment regimens. Bang presented the results from the first 82 patients.
Striking tumor shrinkage observed
“Almost all patients had some degree of tumor shrinkage, even though 59% of the patients had received at least two previous treatments,” Bang reported.
Objective responses were observed in 57% of the cohort (63% when five unconfirmed partial responses are included), and in 80% who had received no prior treatments for advanced disease. The disease control rate (response or stable disease at 8 weeks) was 87%.
At a median follow-up of 6.4 months, median progression-free survival (PFS) had not yet been reached but is projected to be 72% at 6 months. Seventy-seven percent of patients remain on treatment, including seven patients for more than 1 year, he said.
Treatment-related adverse events included nausea (52%), diarrhea (46%), vomiting (43%), and visual disturbance (42%), but virtually all were grade 1 and they tended to resolve over the course of treatment.
Based on these preliminary findings, Bang maintained that “for patients with ALK-positive NSCLC, crizotinib may offer a potential new standard of care.”
According to Martin Edelman, MD of the University of Maryland Greenebaum Cancer Center, Baltimore, the paper’s invited discussant, crizotinib should provide a targeted approach to patients ineligible for inhibitors of the epidermal growth factor receptor (EGFR). A search for EML4/ALK mutations will likely be added to the emerging strategy of testing for mutations in NSCLC, he said.
Edelman predicted that crizotinib may eventually change practice but the drug is not yet commercially available. An ongoing phase 3 trial is likely to be positive, “considering the results today,” he said, and the drug should become “a major treatment advance” for this subset.
