MA07.01 Updated Pooled Analysis of CNS Endpoints in Two Phase II Studies of Alectinib in ALK+ NSCLC

Abstract

Based on two single-arm, multicenter, phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]), the FDA approved the ALK inhibitor alectinib for use in ALK+ NSCLC patients after prior crizotinib. Alectinib was well tolerated in both phase II studies and showed efficacy against both systemic and central nervous system (CNS) disease, the latter being a common progression site in ALK+ NSCLC. This analysis uses pooled data from the latest cut-offs (22 Jan 2016 for NP28761; 1 Feb 2016 for NP28673) to examine the long-term CNS efficacy of alectinib. Both studies enrolled crizotinib-refractory patients ≥18 years with ECOG PS 0–2 and locally advanced or metastatic ALK+ NSCLC (confirmed by FDA-approved test). CNS metastases were permitted if asymptomatic. Patients received 600mg oral alectinib BID. The primary endpoint in both studies was objective response rate (ORR) by independent review committee; secondary CNS endpoints included CNS ORR, CNS duration of response (DoR), and CNS disease control rate (DCR). CNS response and progression were determined by RECIST v1.1. All patients had baseline imaging to assess CNS metastases, with further imaging every 6 or 8 weeks for NP28761 and NP28673, respectively. The overall pooled analysis population comprised 225 patients (n=87 from NP28761; n=138 from NP28673); median follow-up for this updated analysis was 18.8 (0.6–29.7) months (>6 months additional follow-up). At baseline, 50 patients had measurable and 86 had non-measurable CNS disease; together, these groups comprised 136 patients, 60% of the overall pooled population. Seventy percent of patients had prior CNS radiotherapy; 58% of these completed radiotherapy >6 months before study entry. Updated CNS data are shown in the Table and are consistent with systemic results.Tabled 1Measurable CNS disease at baseline (n=50)Measurable and non-measurable CNS disease at baseline (n=136)CNS ORR, n (%) [95% CI]32 (64.0) [49.2–77.1]60* (44.1) [35.6–52.9]Complete response (CR), n (%)11 (22.0)39* (28.7)CNS DCR, n (%) [95% CI]45 (90.0) [78.2–96.7]117 (86.0) [79.1–91.4]Median CNS DoR, months [95% CI] Patients with event, n (%)11.1 [7.6–NE] 18 (56.3)13.8 [11.0–21.5] 32 (53.3)* N.B. Non-measurable disease response can only be classified as CR, non-CR/non-progressive disease (PD) or PD. Open table in a new tab * N.B. Non-measurable disease response can only be classified as CR, non-CR/non-progressive disease (PD) or PD. This updated pooled analysis with mature data confirms that alectinib can provide long-term control of CNS metastases in ALK+ NSCLC, with a high CR rate.