On September 28, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present new data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 congress, the results of a number of studies in patients receiving Alecensa (alectinib) for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, SEP 28, 2019, View Source [SID1234539877]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data presented at ESMO (Free ESMO Whitepaper) this year further demonstrate the well-established benefits of Alecensa, and confirm its use as the standard of care for newly diagnosed advanced or metastatic ALK-positive lung cancer patients," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The positive results from our real-world data study further support the benefits we have seen from our Phase III clinical studies."

Real-world data results in patients with ALK-positive NSCLC
Insights utilising real-world data from the Flatiron Health database will be presented at the congress on Saturday 28 September (Abstract #1546P, 12:00 CEST). These data further support the benefits of Alecensa in the real-world setting, where real-world progression free survival (rwPFS), time to treatment discontinuation (TTD – used as a surrogate for real-world treatment duration) and overall survival (OS) were demonstrated to be longest in Alecensa treated patients with previously untreated ALK-positive NSCLC. The results also show that despite the established benefit of individual ALK inhibitors (ALKi) as first-line therapies and the inclusion of ALKi in many clinical guidelines, as recently as 2017 and 2018 more than 25% of patients with ALK-positive NSCLC received a non-ALKi as first-line therapy. Data were available for 620 patients with ALK-positive advanced NSCLC.

1L, first-line therapy; ALKi, ALK inhibitor; rwPFS, real-world progression-free survival; TTD, time to treatment discontinuation; OS, overall survival; NR, not reached (median survival estimate could not be calculated). 6 & 12-month probability is the event-free survival probability for the following events: progression, treatment discontinuation and death at 6 months and at 12 months, respectively.

Final PFS and updated Phase III ALEX data
Final PFS and updated results from the pivotal Phase III ALEX study, to be presented on Sunday 29 September during a poster discussion (Abstract #1484PD, 16:30 CEST), confirm the superior efficacy and tolerability of Alecensa in comparison to crizotinib in patients with untreated ALK-positive NSCLC, reducing the risk of disease worsening or death by 57% (hazard ratio [HR]=0.43, 95% CI: 0.32–0.58). Mature data show that Alecensa provides a median investigator-assessed progression free survival (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.

Alecensa also demonstrated superior efficacy compared to crizotinib regardless of the presence of central nervous system (CNS) metastases at baseline. For those with CNS metastases, the median investigator-assessed PFS was 25.4 months for Alecensa versus 7.4 months for crizotinib (HR=0.37, 95% CI: 0.23–0.58). In those without CNS metastases, it was 38.6 months versus 14.8 months respectively (HR=0.46, 95% CI: 0.31–0.68). Despite longer median treatment duration with Alecensa versus crizotinib (27.7 months versus 10.8 months), the safety profile for Alecensa remains favourable; fewer Alecensa-treated patients experienced Grade 3–5 adverse events (AEs) (48.7% versus 55.0% crizotinib).

BFAST
On Monday 30 September (08:30 – 10:00 CEST, Abstract LBA81), Roche will also present results from the first cohort of the Phase II/III Blood First Assay Screening Trial (BFAST). BFAST is the first prospective trial to use blood-based next generation sequencing (NGS) as the sole method of identifying and assigning NSCLC patients to targeted therapy based on actionable genetic alterations without the need for tissue biopsy. The study utilised FoundationOne Liquid, Foundation Medicine’s liquid (blood) biopsy assay to detect fusions in circulating tumour DNA (ctDNA) from a simple blood draw to identify ALK status and consequently eligibility for Alecensa.

About the ALEX Study
ALEX (NCT02075840/B028984) 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 whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. Patients were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study was PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (ORR), duration of response (DOR) and OS. The multicentre study was conducted in 303 people across 161 sites in 31 countries. OS data continue to be considered immature.

About the real-world data Study
The real-world data study is a retrospective cohort study that utilised US electronic health record data from Flatiron Health, a nationwide database containing de-identified patient-level structured and unstructured data, curated via technology-enabled abstraction. Treatment patterns and outcomes, including real-world progression free survival (rwPFS) and overall survival (OS) were extracted for first- or second-line therapy. Time to treatment discontinuation (TTD) was used as a surrogate for real-world treatment duration accounting for treatment beyond progression. Time-to-event analyses were performed using Kaplan-Meier methods. Patients included were diagnosed with stage IIIB-IV ALK-positive NSCLC between 01 January 2011 and 30 September 2018. Data were available for 620 patients with ALK-positive advanced NSCLC. An ALKi was given to 420/620 (67.7%) patients as first-line therapy.

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. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is now approved in 83 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the US, Europe, Japan and China.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.