ESMO: Roche’s Alecensa claims a first in ALK-positive NSCLC

Roche’s Alecensa has become the first drug in the ALK inhibitor class to significantly improve disease-free survival across all disease stages in a phase 3 trial involving patients with ALK-positive non-small cell lung cancer (NSCLC).

The findings – trumpeted as “practice-changing” at the symposium during the ESMO conference – came from an interim analysis of data that found a 76% improvement in DFS for Alecensa (alectinib) compared to platinum-based chemotherapy when used as adjuvant treatment after surgery.

Two-year DFS rates with Alecensa and chemotherapy were 93.8% and 63.0%, respectively, after around 28 months’ follow-up, and Roche’s drug also showed a 78% reduction in disease recurrence or death related to recurrence of the cancer in the central nervous system, a common area of relapse following surgery in patients with ALK-positive NSCLC.

“The findings […] will absolutely help to change practice, as they give a very clear signal, in a head-to-head comparison with chemotherapy, that adjuvant targeted treatment with alectinib improves DFS in this setting,” said Professor Martin Reck from the Lung Clinic Grosshansdorf in Germany, who presented the results at ESMO.

Roche said that with about one in two people with early-stage NSCLC experiencing disease recurrence following surgery, despite adjuvant chemotherapy, more effective treatment options are urgently needed to provide the best chance for a cure.

“Alecensa can potentially alter the course of this disease as we aim to provide the best chance for cure,” said Roche’s chief medical officer, Levi Garraway.

The company said it plans to file the data with global regulatory authorities, including the FDA in the US and EMA in the EU. Meanwhile, the patients in ALINA are continuing to be followed to see if the DFS improvement translates to an increase in overall survival, a secondary endpoint.

Around 5% of all NSCLC cases carry ALK mutations, and patients with advanced disease have multiple treatment options, including Alecensa, Takeda’s Alunbrig (brigatinib), and Novartis’ Zykadia (ceritinib), as well as Pfizer’s older therapy Xalkori (crizotinib) and follow-up Lorbrena (lorlatinib).

Roche is vying to become the first company to get approval for an ALK inhibitor in early-stage NSCLC and seems to be firmly in front of its rivals with that plan, as there is no indication that any of the other companies are testing their ALK inhibitors in this setting.

There are some answers still needed to gauge Alecensa's potential role in this setting, according to Reck.

“We need to look at biomarkers and to investigate if the effect of alectinib is homogeneous across ALK translocations or if there is a different variant partner, or a specific variant, that is indicative of a particularly good response – or, conversely, a detrimental effect – with treatment,” he told the congress.