Roche’s immunotherapy MPDL3280A better than chemotherapy in improving overall survival in NSCLC patients

Data to be presented at the 51^st Annual Meeting of the American Society of Clinical Oncology (ASCO) suggest that the investigational immunotherapy MPDL3280A may double the likelihood of overall survival in the study period (HR=0.47), compared with docetaxel chemotherapy, in individuals with non-small cell lung cancer (NSCLC) who expressed the highest levels of PD-L1 (a receptor present on cancer cells). This Phase II study (POPLAR) in people with previously treated NSCLC is the first trial of its kind to show that inhibiting PD-L1 increases the activity of the immune system which prevents disease progression and may improve survival.

Lung cancer is Britain’s biggest cancer killer, responsible for 6% of all deaths in the UK. With around 43,500 new cases diagnosed every year, less than 30% of UK lung cancer patients will be alive one year after diagnosis. POPLAR, a randomised, multi-centre, global study in NSCLC included patients from The Royal Free Hospital, Charing Cross Hospital and Guy’s and St Thomas’ Hospital in London, and The Christie in Manchester.

Through immunohistochemistry testing (IHC), researchers were able to identify individuals with a medium or high expression of PD-L1 on tumour cells and who appear to be most likely to experience improvement in overall survival, progression free survival and overall response rate. Conversely this also enabled researchers to identify those who were unlikely to benefit versus standard of care due to low PD-L1 expression.

An improvement in survival was also observed in people who had medium and high (HR=0.56) or any level of PD-L1 expression (HR=0.63), as characterised by the IHC test being developed by Roche, demonstrating that this treatment option could improve survival of any individual if they have some PD-L1 cell expression.

There were no unexpected toxicities experienced with MPDL3280A. It was generally well-tolerated and adverse events were consistent with what has been previously reported for MPDL3280A in NSCLC. Roche has a further three Phase II and six Phase III studies of MPDL3280A ongoing in various types of lung cancer. MPDL3280A has shown potential in other areas of unmet need including urothelial bladder cancer of which Phase Ia data is being presented at ASCO.

Reinforcing Roche’s commitment to lung cancer, Roche also presented positive results from two pivotal studies for alectinib, an oral investigational anaplastic lymphoma kinase (ALK) inhibitor which has been shown to shrink tumours (overall response rate, ORR: 50% and 47.8%, respectively) in people with advanced ALK positive (ALK+) NSCLC, whose disease had progressed following treatment with crizotinib.

Brain metastasis is highly prevalent in patients with ALK+ NSCLC. Importantly, these studies show that alectinib shrunk tumours in the central nervous system (CNS) (CNS ORR: 57.1% and 68.8%, respectively) and is therefore able to pass through the blood-brain barrier, the body’s natural filter and defence to protect the brain. In addition, patients whose tumours had shrunk with alectinib were continuing to respond for a median of 11.2 and 7.5 months respectively.

Alectinib demonstrated a safety profile that was consistent with that observed in previous studies. The most commonly reported adverse events included an increase in muscle enzymes (increased blood levels of creatinine phosphokinase), increased liver enzymes and shortness of breath.

Both investigational drugs MPDL3280A and alectinib have received Breakthrough Therapy Designation from the FDA – an initiative designed to accelerate the development and review of medicines intended to treat serious diseases and drive patient access through FDA approval.

The European regulatory filings for these indications are still at an early stage as the pivotal trials are currently ongoing. Once the data is available, Roche will liaise with the appropriate health authorities to ensure that patients and doctors receive this therapeutic option as soon as possible.