AstraZeneca stops lung cancer trial early, after star drug Tagrisso induces 'overwhelming' efficacy
A pivotal lung cancer trial testing Tagrisso, AstraZeneca’s bestselling oncology therapy, has been halted due to “overwhelming” efficacy.
The 682 patient-trial, ADAURA, was evaluating the drug against a placebo in non-small cell lung cancer patients with EGFR mutations who had undergone tumor resection and optional, standard postoperative adjuvant chemotherapy. In the Tagrisso arm, patients were to be treated with the 80 mg drug once-daily for three years, or until the cancer returned — and the data readout was scheduled for 2022.
The trial, in which the main goal was disease-free survival (DFS), was stopped on the recommendation of an independent data monitoring committee based on its determination of “overwhelming efficacy,” the British drugmaker said, adding that the company would continue to assess the secondary endpoint of overall survival.

No new safety concerns were reported, and detailed data will be presented at a later date. Plans for regulatory submissions are also underway. “Lung cancer is a devastating diagnosis and for the first time an EGFR-targeted medicine can now provide the hope of a cure,” said José Baselga, executive VP of Oncology R&D, in a statement.
Tagrisso, known chemically as osimertinib, generated sales of more than $3 billion in 2019, is one of AstraZeneca’s flagship oncology therapies.
The drug is already approved as the first line of defense in patients with metastatic EGFR mutation-positive NSCLC.
Lung cancer is the leading cause of cancer death globally, according to the WHO. The two main types of lung cancer are non-small cell and small cell, and NSCLC accounts for about 85% of all cases. Mutations in the EGFR gene occur in 10% to 35% of patients with NSCLC — and the use of EGFR tyrosine kinase inhibitors (TKIs) has transformed the arsenal of tools used to fight the deadly disease.
Despite initial benefit with first-generation EGFR TKIs, such as erlotinib (Roche’s Tarceva) and gefitinib (AstraZeneca’s own Iressa), most patients develop drug resistance within one year. The use of second-generation TKIs such as afatinib (Boehringer Ingelheim’s Gilotrif) and dacomitinib (Pfizer’s Vizimpro) showed promising preclinical activity, dose-limiting toxicity precluded their use in NSCLC patients.
Tagrisso is a third-generation EGFR TKI. This Tagrisso trial is the first to demonstrate the benefit of targeted EGFR inhibition in the adjuvant NSCLC setting and the drug will likely gain approval in this indication by 2021 with no competitors in sight, wrote Cowen analyst Steve Scala in a note.
The addition of resected stage (IB-IIIA) NSCLC patients to the Tagrisso label could increase the global addressable population by over 60,000 patients (including China; currently >250,000 in the metastatic setting), and duration of treatment may exceed that in advanced patients (median 20.7 months in the FLAURA trial). Advanced NSCLC typically presents in the metastatic setting, so the cannibalization of existing sales is not expected, he said.
“The positive DFS was observed about 2 years ahead of the 2022 estimated primary completion date, indicating robust efficacy that increases the likelihood of ultimately achieving OS…ADAURA was powered to detect DFS HR of 0.78, but likely surpassed this value. This news also raises the prospect of an early readout for Phase III LAURA in EGFRm unresectable Stage III NSCLC (currently due in 2022), representing ~70,000 additional patients.”
Together with LAURA, ADAURA approval is critical for Tagrisso to surpass AstraZeneca’s initial peak sales projections of $4 billion to $5 billion, he added, estimating the drug is poised to eclipse $8 billion in peak sales in 2025.
Considered one of the most commercially rewarding conditions to treat, AstraZeneca had pinned its hopes on the combination of its checkpoint inhibitor Imfinzi with its in-house CTLA-4 drug tremelimumab in the keenly watched MYSTIC trial in 2018, but that bet proved costly. Imfinzi is now in development as a monotherapy, as well as a tremelimumab and/or chemotherapy combination, in various trials for lung cancer patients without a known genetic mutation.
In late 2018, AstraZeneca executed a number of deals pruning its portfolio and reinvigorating its focus on new flagship products, notably cancer drugs such as Lynparza, Imfinzi, Tagrisso, and Calquence. By 2019, CEO Pascal Soriot also revamped the company’s structure — dissolving the company’s MedImmune subsidiary, enshrining the oncology franchise under one roof, and shifting the rest of the pipeline under a separate division.
Buoyed by the performance of its oncology drugs, last year AstraZeneca bet big to partner with Daiichi Sankyo on a cancer drug, with $1.35 billion upfront in a deal worth up to roughly $7 billion. Roughly 8 months later, as 2019 drew to a close, the FDA swiftly approved the drug — trastuzumab deruxtecan — for use in breast cancer, months ahead of the expected decision date.