On October 22, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it results from the phase III ALESIA study, showing that Alecensa (alectinib) met its primary endpoint of investigator-assessed (INV) progression-free survival (PFS) (Press release, Hoffmann-La Roche, OCT 22, 2018, View Source [SID1234530314]). Alecensa significantly reduced the risk of disease worsening or death by 78%, compared to crizotinib, when given as an initial (first-line) monotherapy treatment in Asian patients with anaplastic lymphoma kinase (ALK)-positive advanced or metastatic non-small cell lung cancer (NSCLC) (hazard ratio [HR]=0.22, 95% CI: 0.13-0.38).[1] Median PFS reported by the investigators was not yet reached in patients who received Alecensa (95% CI: 20.3 months-not reached) versus 11.1 months (95% CI: 9.1-13.0 months) in those who received crizotinib.[1] The safety profile of Alecensa was consistent with that observed in previous studies.[1]
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"The ALESIA study supports the use of Alecensa as the standard of care for newly diagnosed advanced or metastatic ALK-positive lung cancer across multiple populations," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Alecensa has received rapid regulatory approvals for first-line treatment in 65 countries to date, including in China."
Median PFS reported by an independent review committee (IRC), a secondary endpoint, was not yet reached in patients who received Alecensa (95% CI: 16.7 months-not reached), versus 10.7 months (95% CI: 7.4 months-not reached) in patients who received crizotinib (HR=0.37, 95% CI: 0.22-0.61).[1] The phase III ALESIA study also demonstrated that compared to crizotinib, Alecensa reduced the risk of disease progression in the central nervous system (CNS), another secondary endpoint in the study, by 86% (HR=0.14, 95% CI: 0.06-0.30).[1]
The ALESIA data are being officially presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress during a Presidential Symposium on 22 October at 16:30 (Abstract LBA10 Presidential Symposium).[3]
This is the third phase III study to show that Alecensa as a first-line treatment significantly reduced the risk of disease worsening or death (PFS) compared to crizotinib in patients with ALK-positive advanced or metastatic NSCLC.[2;3;4] The results reinforce the findings of the phase III global ALEX study, which found that Alecensa significantly reduced the risk of disease progression or death (PFS) by 57% (HR=0.43, 95% CI: 0.32-0.58) compared to crizotinib after two years of follow-up in people with ALK-positive metastatic NSCLC, as assessed by the investigator.[3] The ALEX study also showed that Alecensa more than tripled median PFS to nearly three years (34.8 months, 95% CI: 17.7 months-NE) compared to crizotinib (10.9 months, 95% CI: 9.1-12.9 months) and demonstrated superior efficacy compared to crizotinib regardless of the presence of CNS metastases at baseline, a secondary endpoint.[3] INV median PFS for people without CNS metastases at baseline was 34.8 months with Alecensa (95% CI: 22.4 months-NE) versus 14.7 months (95% CI: 10.8-20.3 months) with crizotinib (HR=0.47, 95% CI: 0.32-0.71).[3] INV median PFS for people with CNS metastases at baseline was 27.7 months in the Alecensa arm (95% CI: 9.2 months-NE) versus 7.4 months (95% CI: 6.6-9.6 months) in the crizotinib arm (HR=0.35, 95% CI: 0.22-0.56).[3]
The ALESIA study was a bridging study, designed to show consistency with the phase III ALEX study and was not powered to show superiority vs crizotinib. It completes a post-approval agreement with the National Drug Administration of China (CNDA) to demonstrate consistency between the ALESIA and ALEX studies, following the priority review and rapid approval of Alecensa in August this year.[5] The regulatory approval in China is one of the latest of 65 countries for the use of Alecensa as a first-line monotherapy for people with ALK-positive NSCLC.[6]
About the ALESIA study[7]
ALESIA (NCT02838420) is a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Alecensa versus crizotinib, and the pharmacokinetics of Alecensa in Asian patients with treatment-naive ALK-positive advanced or metastatic NSCLC. Patients were randomised (2:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALESIA study is PFS as assessed by the investigator using the RECIST v1.1 criteria. Secondary endpoints include: PFS, time to CNS progression and CNS ORR assessed by IRC, objective response rate and duration of response assessed by the investigator, overall survival, health-related quality of life and safety. The multicentre study was conducted in 187 patients across 21 sites in three countries.
About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive.[6] ALK-positive NSCLC is often found in younger people who have a light or non-smoking history.[8] It is almost always found in people with a specific type of NSCLC called adenocarcinoma.[8] Alecensa is now approved in 65 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the US, Europe, Japan and China.[6]