Last week, AstraZeneca announced that its combination of Imfinzi (durvalumab) + chemotherapy, with or without tremelimumab, met its key endpoint of improving progression-free survival (PFS) when compared to the standard of care, platinum-based chemotherapy alone, in the Phase III POSEIDON trial.
The trial investigated the triplet combination as a first-line treatment in previously untreated patients with non-squamous and squamous stage IV (metastatic) non-small cell lung cancer (NSCLC) and the full range of PD-L1 expression levels but without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations. The trial will continue to assess the additional primary endpoint of overall survival (OS), with data anticipated in 2020. With no further trial details released at present, AstraZeneca plans to present the results at a forthcoming medical meeting, as well as sharing the results with regulators.
NSCLC accounts for approximately 85% of lung cancers and has a poor prognosis, with a five-year survival rate as low as 6% for patients with metastatic disease. One of the main unmet needs in NSCLC treatment is the need for more effective first-line treatment options that provide OS benefits to patients with no actionable mutations. Imfinzi and the experimental candidate, tremelimumab, are monoclonal antibodies classified as immuno-oncology (IO) treatments as they target PD-L1 and CTLA-4 proteins on tumour cells, respectively, contributing to T-cell activation and boosting the body’s immune response against cancer. The promise of IO therapies as life-changing cancer treatments for NSCLC was realized with the approval of Bristol-Myers Squibb ’s Opdivo (nivolumab) and Merck & Co.’s Keytruda (pembrolizumab) in 2015, Roche ’s Tecentriq (atezolizumab) in 2016, and Imfinzi in 2018.
Previous failures in the Phase III NEPTUNE and MYSTIC trials lowered expectations of success for the Imfinzi and tremelimumab combination in the treatment of metastatic NSCLC; however, the odds seem to have changed. Nonetheless, there is a lingering amount of scepticism as to whether the more costly and potentially more toxic three-drug regimen of Imfinzi + chemotherapy + tremelimumab would succeed as a first-choice treatment for prescribers, even considering the added clinical benefit. AstraZeneca seems to be covering all possible bases and is also trialling Imfinzi as a monotherapy in the Phase III PEARL study and in various other drug combinations to assess its effectiveness in metastatic NSCLC.
Several big pharma competitors are also placing NSCLC as a major area for the development and commercialisation of IO treatments, both as monotherapy and in combination with other IO agents. The demand and uptake of IO therapies over targeted therapies and chemotherapies in NSCLC has risen significantly, and GlobalData estimates that by 2025 IO therapies will represent over 50% of the total NSCLC market in the eight major markets (8MM: US, France, Germany, Italy, Spain, the UK, Japan, and China).