AZ cancer drugs chalk up wins in early-stage lung cancer

AstraZeneca’s efforts to move its top oncology drugs into earlier treatment settings have been lifted by positive data for Tagrisso and Imfinzi in lung cancer.

AZ and other cancer drug developers are trying to move their therapies into adjuvant (post-surgery) and neoadjuvant (pre-surgery) use, in the hope of reducing relapse rates and raising the prospects of curing the cancer.

Up to 30% of all patients with NSCLC are diagnosed early enough to have surgery with the hope of a cure, but between a third and half of them experience a recurrence and need additional lines of treatment.

EGFR inhibitor Tagrisso (osimertinib) has now become the first drug to show an improvement in overall survival (OS) in patients with early-stage, EGFR-mutated non-small cell lung cancer (NSCLC) after surgery intending to cure the disease.

The finding comes from the phase 3 ADAURA trial, and comes almost three years after Tagrisso was shown to improve disease-free survival, earning it approval as the first EGFR inhibitor for adjuvant treatment of NSCLC with EGFR mutations in December 2020.

It was widely anticipated that Tagrisso could show an improvement in overall survival, given a DFS improvement of 83% at the first readout and a median DFS of nearly five and a half years when an ADAURA update was presented at the ESMO congress last September. AZ isn’t revealing the OS improvement yet, but said it will do so at a future medical meeting.

Moving Tagrisso into the adjuvant setting in early lung cancer, adding to its use as first- and second-line therapy for more advanced NSCLC tumours helped sales of the drug accelerate to almost $5.5 billion last year – making it AZ’s top-selling drug by some margin – and the OS results shore up its leadership position in the EGFR inhibitor class.

AZ has also reported new data this week from the AEGEAN study of PD-L1 inhibitor Imfinzi (durvalumab) in the phase 3 AEGEAN trial, which looked at the drug as a neoadjuvant regimen with chemotherapy and as adjuvant monotherapy in patients with early-stage NSCLC, irrespective of PD-L1 biomarker levels, that was treatable with surgery.

The new data on event-free survival (EFS) show an improvement for neoadjuvant Imfinzi plus chemo compared to neoadjuvant chemo alone, backing up results reported last year showing improved pathologic complete responses (pCR) and major pathologic responses (mPR) with the combination. Once again, the actual EFS data will be presented later.

AZ is playing catch-up in neoadjuvant NSCLC with Bristol-Myers Squibb, which claimed an FDA approval for its PD-1 inhibitor Opdivo (nivolumab) in this indication in 2021 on the strength of the CheckMate-816 study, which showed a 37% improvement in EFS in patients regardless of PD-L1 status.

Meanwhile, in the adjuvant setting, Roche has approval for its PD-L1 inhibitor Tecentriq (atezolizumab) after surgery and platinum-based chemotherapy in patients with NSCLC tumours in which 1% or more cells express PD-L1.

AZ said it plans to share the data with regulators with a view to extending the approved indications of Imfinzi, which is already used in advanced NSCLC, as well as bladder and biliary tract cancer, with sales of $2.8 billion last year.