The European Commission has granted marketing authorisation for Imfinzi ( Durvalumab ) as monotherapy for the treatment of locally-advanced, unresectable non-small cell lung cancer ( NSCLC ) in adults whose tumours express PD-L1 on gretaer than or equal to 1% of tumour cells and whose disease has not progressed following Platinum-based chemotherapy and radiation therapy ( CRT ).
Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
The approval is based on results from PACIFIC, a phase III, randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in all-comer patients ( i.e. regardless of PD-L1 status ) with unresectable, stage III ( locally-advanced ) NSCLC whose disease has not progressed following Platinum-based chemotherapy and radiation therapy.
The trial is being conducted in 235 centres across 26 countries involving 713 patients.
The primary endpoints of the trial are progression-free survival ( PFS ) and overall survival ( OS ), and secondary endpoints include landmark PFS and OS, objective response rate ( ORR ), and duration of response ( DoR ).
The most common adverse reactions ( greater than or equal to 20% of patients ) of Durvalumab versus placebo were cough ( 40.2% vs. 30.3% ), upper respiratory tract infections ( 26.1% vs 11.5% ) and rash ( 21.7% vs 12.0% ).
12.8% of patients experienced a grade 3 or 4 adverse effects with Imfinzi vs 9.8% with placebo.
Stage III ( locally-advanced ) NSCLC is divided into three sub-categories ( IIIA, IIIB and IIIC ), defined by how much the cancer has spread locally and the possibility of surgery.
Stage III disease is different from stage IV disease, when the cancer has spread ( metastasised ) to distant organs, as stage III is currently treated with curative intent.
Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-eight countries ( China, France, Germany, Italy, Japan, Spain, UK, US ) in 2017.
The majority of stage III NSCLC patients are diagnosed with unresectable tumours.
No new treatments beyond chemoradiation therapy, followed by active surveillance to monitor for progression, have been available to patients for decades. ( Xagena )
Source: AstraZeneca, 2018