(ChemotherapyAdvisor) – The oral small molecule crizotinib significantly prolongs progression-free survival (PFS) times for the 3% to 4% of patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor the anaplastic lymphoma kinase (ALK) mutation, according to a phase 3 study presented at the European Society for Medical Oncology (ESMO) annual meeting in Vienna, Austria. 

Patients who received crizotinib demonstrated a median PFS of 7.7 months versus 3 months among patients who were administered docetaxel or pemetrexed (HR 0.49 [95% CI: 0.37–0.64]; P<0.0001), reported Alice T. Shaw, MD, PhD, a thoracic oncologist at the Massachusetts General Hospital Cancer Center in Boston, and her coauthors.

“These findings establish crizotinib as the standard of care for patients with previously treated advanced ALK+ NSCLC,” Dr. Shaw reported. “Compared with chemotherapy, crizotinib is associated with significantly greater improvement from baseline in both lung cancer symptoms and quality of life.”

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Objective response rate (ORR) was also significantly higher among patients receiving crizotinib than docetaxel or pemetrexed (65% vs 20%; P<0.0001), the authors reported.

The researchers randomized 347 patients with stage IIIB/IV ALK-positive NSCLC who had previously received one platinum-based chemotherapy to receive 250 mg PO BID crizotinib (n=173 patients) or either pemetrexed 500 mg/m2 or D 75 mg/m2 IV q3w (n=174; 58% P, 42% docetaxel).

The most common treatment-related adverse events among patients receiving crizotinib were visual disturbance (59%), diarrhea (53%), nausea (52%), vomiting (44%), and elevated transaminases (36%), the authors reported. For patients receiving docetaxel or pemetrexed, common toxicities included nausea (35%), fatigue (29%), neutropenia (22%), decreased appetite (21%), and alopecia (20%). 

“The incidence of grade 3/4 TRAE was the same for crizotinib vs pemetrexed/docetaxel (31%),” the authors reported. “The incidence of TRAE leading to discontinuation was 6% for C vs 10% for P/D. Duration of treatment was longer for crizotinib vs pemetrexed/docetaxel (median cycles started 11 vs 4).”

“No statistically significant difference in overall survival (OS) was observed between crizotinib and chemotherapy, but the interim analysis was immature and may have been confounded by crossover,” Dr. Shaw noted.

NSCLC chromosomal inversions and translocations activate ALK in 3% to 4% of cases of NSCLC.  

ESMO Abstract (#LBA1_PR)