Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 34; no. 34; pp. 4079 - 4085
• Main Authors: Gadgeel, Shirish M, Shaw, Alice T, Govindan, Ramaswamy, Gandhi, Leena, Socinski, Mark A, Camidge, D Ross, De Petris, Luigi, Kim, Dong-Wan, Chiappori, Alberto, Moro-Sibilot, Denis L, Duruisseaux, Michael, Crino, Lucio, De Pas, Tommaso, Dansin, Eric, Tessmer, Antje, Yang, James Chih-Hsin, Han, Ji-Youn, Bordogna, Walter, Golding, Sophie, Zeaiter, Ali, Ou, Sai-Hong Ignatius
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 01-12-2016
• Subjects: Adult; Aged; Carbazoles - administration & dosage; Carbazoles - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - secondary; Crizotinib; Endpoint Determination; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medicin och hälsovetenskap; Middle Aged; ORIGINAL REPORTS; Piperidines - administration & dosage; Piperidines - therapeutic use; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Treatment Outcome
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2016.68.4639

Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.