IMpower131 trial: Atezolizumab plus chemotherapy reduces the risk of disease worsening or death in the initial treatment of people with advanced squamous non-small cell lung cancer
IMpower131 study met its co-primary endpoint of progression-free survival and demonstrated that the combination of Atezolizumab ( Tecentriq ) plus chemotherapy ( Carboplatin and Abraxane [ albumin-bound Paclitaxel; nab-Paclitaxel ] ) reduced the risk of disease worsening or death ( progression-free survival; PFS ) compared with chemotherapy alone in the initial ( first-line ) treatment of people with advanced squamous non-small cell lung cancer ( NSCLC ).
Safety for the Atezolizumab and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.
At this interim analysis a statistically significant overall survival ( OS ) benefit was not observed and the study will continue as planned.
Squamous non-small cell lung cancer is difficult to treat and there have been limited new treatment options over the last few decades.
As per the statistical analysis plan in IMpower131, Arm B ( Atezolizumab plus Carboplatin and nab-Paclitaxel ) must demonstrate a statistically significant overall survival result versus Arm C ( Carboplatin and nab-Paclitaxel ), before an analysis between Arm A ( Atezolizumab plus Carboplatin and Paclitaxel ) and Arm C can be made for progression-free survival and overall survival.
IMpower131 is a phase III, open-label, multicentre, randomised study evaluating the efficacy and safety of Atezolizumab in combination with Carboplatin and nab-Paclitaxel or Atezolizumab in combination with Carboplatin and Paclitaxel versus chemotherapy ( Carboplatin and nab-Paclitaxel ) alone in people with stage IV squamous NSCLC who have not been previously treated with chemotherapy.
The study enrolled 1,021 people who were randomised equally ( 1:1:1 ) to receive: Atezolizumab plus Carboplatin and Paclitaxel ( Arm A ); or, Atezolizumab plus Carboplatin and nab-Paclitaxel ( Arm B ); or, Carboplatin and nab-Paclitaxel ( Arm C, control arm ).
During the treatment-induction phase, people in Arm A received four or six cycles of Atezolizumab plus Carboplatin and Paclitaxel , given on day one of each 21-day cycle.
This was followed by maintenance therapy with Atezolizumab every three weeks until progression of the cancer, or for as long as clinical benefit was observed.
During the treatment-induction phase, people in Arm B received four or six cycles of Atezolizumab, Carboplatin and nab-Paclitaxel. Atezolizumab and Carboplatin were administered on day one of each 21-day cycle. Nab-Paclitaxel was administered on days one, eight and 15 of each 21-day cycle. This was followed by maintenance therapy with Atezolizumab every three weeks until progression of the cancer, or for as long as clinical benefit was observed.
During the treatment-induction phase, people in Arm C received four or six cycles of Carboplatin and nab-Paclitaxel. Carboplatin was administered on day one of each 21-day cycle, and nab-Paclitaxel was administered on days one, eight and 15 of each 21-day cycle. In the maintenance phase, participants received best supportive care.
The co-primary endpoints were: progression-free survival as determined by the investigator using RECIST v1.1 in the intention-to-treat ( ITT ) population ( Arm B versus Arm C ); overall survival in the ITT population ( Arm B versus Arm C ).
IMpower131 met its progression-free survival co-primary endpoint per study protocol. This analysis of IMpower131 evaluated Arm B versus Arm C.
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors.
By inhibiting PD-L1, Atezolizumab may enable the activation of T cells.
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.
Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.
NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope. The squamous form tends to grow near the centre of the lung, and accounts for approximately 25-30% of all NSCLC cases. ( Xagena )
Source: Roche, 2018