uality of Life and global Health Status measures (LCSS [p<0.001], QLQ-C30, [p<0.001] and EQ-5D-5L index [p<0.001]).
In Study A2301, 44 patients with measurable brain metastasis at baseline and at least one post-baseline brain radiological assessment (22 patients in the ceritinib arm and 22 patients in the chemotherapy arm) were assessed for intracranial response by BIRC neuro-radiologist per modified RECIST 1.1 (i.e. up to 5 lesions in the brain). The overall intracranial response rate (OIRR) was higher with ceritinib (72.7%, 95% CI: 49.8, 89.3) as compared to the chemotherapy arm (27.3%, 95% CI: 10.7, 50.2).
The median PFS by BIRC using RECIST 1.1 was longer in the ceritinib arm compared to the chemotherapy arm in both subgroups of patients with brain metastases and without brain metastases. The median PFS in patients with brain metastases was 10.7 months (95% CI: 8.1, 16.4) versus 6.7 months (95% CI: 4.1, 10.6) in the ceritinib and chemotherapy arms, respectively, with HR=0.70 (95% CI: 0.44, 1.12). The median PFS in patients without brain metastases was 26.3 months (95% CI: 15.4, 27.7) versus 8.3 months (95% CI: 6.0, 13.7) in the ceritinib and chemotherapy arms, respectively, with HR=0.48 (95% CI: 0.33, 0.69).
Previously treated ALK-positive advanced NSCLC - randomised phase 3 Study A2303 (ASCEND-5)
The efficacy and safety of Zykadia for the treatment of ALK-positive advanced NSCLC patients who have received previous treatment with crizotinib, was demonstrated in a global multicentre, randomised, open-label phase 3 Study A2303.
A total of 231 patients with advanced ALK positive NSCLC who have received prior treatment with crizotinib and chemotherapy (one or two regimen including a platinum-based doublet) were included in the analysis. One hundred fifteen (115) patients were randomised to Zykadia and one hundred sixteen (116) were randomised to chemotherapy (either pemetrexed or docetaxel). Seventy-three (73) patients received docetaxel and 40 received pemetrexed. In the ceritinib arm, 115 patients were treated with 750 mg once daily fasted. The median age was 54.0 years (range: 28 to 84 years); 77.1% of patients were younger than 65 years. A total of 55.8% of patients were female. 64.5% of the study population were Caucasian, 29.4% Asian, 0.4% Black and 2.6% other races. The majority of patients had adenocarcinoma (97.0%) and had either never smoked or were former smokers (96.1%). The ECOG performance status was 0/1/2 in 46.3%/47.6%/6.1% of patients respectively, and 58.0% had brain metastasis at baseline. All patients were treated with prior crizotinib. All except one patient received prior chemotherapy (including a platinum doublet) for advanced disease; 11.3% of the patients in the ceritinib arm and 12.1% of the patients in the chemotherapy arm were treated with two prior chemotherapy regimen for advanced disease.
Patients were allowed to continue the assigned study treatment beyond initial progression in case of continued clinical benefit as per the investigator's opinion. Patients randomised to the chemotherapy arm could further crossover to receive Zykadia upon RECIST-defined disease progression confirmed by BIRC.
The median duration of follow-up was 16.5 months (from randomisation to data cut-off date).
The study met its primary objective demonstrating a statistically significant improvement in PFS by BIRC with an estimated 51% risk reduction in the ceritinib arm compared to chemotherapy arm (see Table 4 and Figure 3). The P |
