Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non–Small Cell Lung Cancer

• Published in: Journal of thoracic oncology 2018-10, Vol.13 (10), p.1539-1548
• Main Authors: Wu, Yi-Long, Lu, Shun, Lu, You, Zhou, Jianying, Shi, Yuan-kai, Sriuranpong, Virote, Ho, James C.M., Ong, Choo Khoon, Tsai, Chun-Ming, Chung, Chin-Hee, Wilner, Keith D., Tang, Yiyun, Masters, Elizabeth T., Selaru, Paulina, Mok, Tony S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; ALK-positive advanced non–small cell lung cancer; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian Continental Ancestry Group; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; chemotherapy; crizotinib; Crizotinib - pharmacology; Crizotinib - therapeutic use; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; phase III; Young Adult
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2018.06.012

The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population. In this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration–time curve of 5–6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point. Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286–0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6–93.2%) with crizotinib versus 45.6% (95% CI: 35.8–55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients. First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.