On Friday 29 May at the ASCO20 Virtual Scientific Programme, Roche presented updated data from the pivotal phase III ALEX clinical study. The updated data show an increased 5-year survival rate with Alecensa

 (alectinib) compared with crizotinib, reinforcing the value of Alecensa to improve outcomes for patients with this disease. The ALEX study is the first global phase III study of a next-generation ALK-inhibitor to demonstrate a clinically meaningful benefit in overall survival (OS) at five years, compared with crizotinib, in ALK-positive NSCLC.

NSCLC represents approximately 85% of all lung cancer cases and, of these, about 5% of patients are ALK-positive, representing a significant patient population.

 Although overall cancer death rates are declining, 5-year survival rates for NSCLC are still shockingly low — estimated to be just 6.1% for those diagnosed between 2009 and 2015.

 With previous standards of care, the majority of patients with ALK-positive NSCLC would see their disease progress within a year.

 The disease also often affects those who least expect it; around 70% of NSCLC patients have never smoked and 50% of patients are younger than 50 years — often playing active, key roles in families and communities.

Alecensa is a highly selective, CNS active, oral medicine that is currently approved in 88 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the US, Europe, Japan and China.

 The ALEX study [NCT02075840] is a randomised, multicentre, open-label, phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve patients with ALK-positive NSCLC. The multicentre study was conducted in 303 adult patients with previously untreated stage III/IV ALK- positive NSCLC, of which 122 patients had CNS metastases at baseline. Patients were randomised (1:1) to receive either Alecensa 600 mg or crizotinib 250 mg twice-daily, until disease progression, toxicity, withdrawal or death. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included independent review committees (IRC)-assessed PFS, objective response rate, OS and safety. The multicentre study was conducted across 161 sites in 31 countries.

The updated ALEX study results revealed a 5-year survival rate of 62.5% (95% CI: 54.3-70.8) in the Alecensa treatment group, versus 45.5% (95% CI: 33.6-57.4) with crizotinib.

 Additionally, the study found that the OS benefit of Alecensa was seen in patients with CNS metastases at baseline (42% reduction in the risk of death versus crizotinib (95% CI: 0.34-1.00)) as well as in those without CNS metastases at baseline (24% reduction in the risk of death versus crizotinib (95% CI: 0.45-1.26)).

 The safety profile of Alecensa was consistent with previous data, with no new safety signals identified.

 The OS data have not yet reached maturity.

Due to the current COVID-19 outbreak and consequent public health concern, the data was presented via a virtual poster discussion session, which went live on the ASCO virtual programme at 8AM EST on Friday 29 May 2020. The presentation was delivered by the ALEX study Steering Committee member Professor Solange Peters, chair of Medical Oncology at the Lausanne University Hospital (CHUV).

“The updated data from the ALEX trial continue to demonstrate the efficacy of alectinib, and this is the first global randomised study of a next-generation ALK-inhibitor to demonstrate a clinically meaningful improvement in overall survival versus crizotinib in treatment-naïve ALK-positive NSCLC,” Professor Peters commented. “The overall survival benefit was confirmed across all sub-groups, including those with central nervous system metastases at baseline.”

Alecensa met the primary endpoint of the pivotal phase III ALEX study in a data readout that was announced in April 2017.

 The mature PFS and updated safety data were later presented at the 2019 European Society for Medical Oncology (ESMO) Annual Meeting during a poster discussion (Abstract #1484PD). The mature PFS data demonstrated that Alecensa provides a median investigator-assessed PFS of nearly three years (34.8 months, 95% CI: 17.7-not reached [NR]) versus 10.9 months (95% CI: 9.1—12.9) in those who received crizotinib.

These updated data from the ALEX study build on Alecensa’s already solid grounding as standard of care in the first-line treatment of ALK-positive NSCLC. The result provides clinicians with greater assurance that Alecensa is the preferred treatment option for improving outcomes for these patients. 

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On Friday 29 May at the ASCO20 Virtual Scientific Programme, Roche presented updated data from the pivotal phase III ALEX clinical study.

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ASCO: New data for Alecensa shows 5-year overall survival in ALK-positive NSCLC