- Roche’s lung cancer drug Alecensa (alectinib) could supplant Pfizer’s Xalkori (crizotinib) as the current standard of care for initial treatment of patients who test positive for an abnormal ALK gene, new research suggests.
- In these ALK-positive patients — a subset that accounts for roughly 5% of non-small cell lung cancers — first-line treatment with Alecensa dramatically extended median progression-free survival over Xalkori by about 15 months, according to research unveiled Monday at the annual meeting of the American Society for Clinical Oncology (ASCO).
- Treatment options for ALK positive lung cancer have progressed rapidly since Xalkori’s approval in 2011 and there are now four such targeted agents approved in the U.S. Alecensa currently holds a roughly 50% share of the second-line market, according to Roche, and the new trial results support expansion into first-line therapy.
Roche announced back in April that its Phase 3 ALEX study comparing Alecenesa to Xalkori met its primary endpoint, but didn’t divulge any details on the magnitude of improvement.
Data to be presented Tuesday at ASCO yet unveiled Monday morning showed Alecensa reduced the risk of cancer progression or death by 53% compared to Xalkori. Median progression-free survival measured 25.7 months for patients on Alecensa and 10.4 months for those on Xalkori, as assessed by an independent review committee.
"This is the first global study to compare [Alecensa] with [Xalkori] in ALK-positive lung cancer and establishes [Alecensa] as the new standard of care for initial treatment in this setting," said Alice Shaw, lead author of the study and director of thoracic oncology at Massachusetts General Hospital Cancer Center, in a statement.
Additionally, Alecensa demonstrated a better ability to penetrate into the brain and prevent brain metastases, with an incidence of only 9% at one year compared to 41% for Xalkori.
Safety was improved as well, with lower rates of Grade 3/4 adverse events, discontinuations or dose reductions.
In the open-label ALEX study, Roche tested Alecensa against Xalkori in 303 patients with stage 3B or stage 4 ALK-positive non-small cell lung cancer.
A changing market
Alecensa’s strong results follows recent regulatory action in the ALK-positive space.
Novartis’ Zykadia (certitinib), the second ALK inhibitor approved after Xalkori, recently secured an expanded label to include front-line treatment. And Takeda’s Alunbrig (brigantinib), acquired in the Japanese drugmaker’s January acquisition of Ariad Pharmaceuticals, won an OK from the Food and Drug Administration just last month.
Ten years ago, the prognosis for ALK-positive lung cancers was much worse. But the emergence of Xalkori, and more powerful ALK inhibitors after it, has shifted both treatment and market dynamics.
"In the US, we are projecting about 4,000 new cases on an annualized basis," explained Mohamed Lahda, Takeda’s U.S. product lead for Alunbrig, in an interview. "This is going to be more of a prevalence driven market. These patients live longer because they are getting better ALK inhibitors and as they progress they go on to the next one and the next one."
Takeda is confident it can take on the incumbent leaders in the space, focusing on Alunbrig’s early evidence of efficacy as well as its ability to penetrate in the brain.
"Based on the breadth of mutational coverage and the [central nervous system] penetration, we think that we have got a really good opportunity and chance to be viewed as a best in class compound and reinforces our belief in being able to move up line into front-line disease," said Ryan Cohlhepp, oncology commercial leader at Takeda Oncology.
Roche’s results with Alecensa could prove hard to beat, however.