AstraZeneca and Medimmune, its global biologics research and development arm, continue to demonstrate their progress in lung cancer research at the IASLC 18th World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Yokohama, Japan, 15-18 October 2017. With 43 data presentations, including 16 oral presentations, AstraZeneca is focusing on four key scientific drivers of progress in lung cancer: treating earlier stages of the disease; strategies to overcome tumour resistance; improved testing to match the right treatments to the right patients; and continued exploration of the potential of immuno-oncology combinations.

Sean Bohen, executive vice president, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The data we are presenting at WCLC 2017 illustrate the science-led strength of our clinical programme focused on tackling multiple mechanisms associated with this complex disease. We are constantly striving to deliver on our ambition of one day eliminating cancer as a cause of death.”

Treating lung cancer at earlier stages of the disease

To date, the majority of research has been focused on metastatic disease, where the medical need is most urgent. But with the potential for clinical benefit becoming clearer in earlier stages of disease, long-term quality of life is an increasingly important component in deciding the right treatment.

At WCLC, patient-reported outcomes from the Phase III Imfinzi PACIFIC trial will be presented during the Presidential Symposium. The PACIFIC trial of Imfinzi (durvalumab) in patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) who have not progressed following platinum-based chemoradiation therapy, is the first to demonstrate superior progression-free survival (PFS) in this setting.

Rina Hui, MD, PhD, clinical associate professor of medicine, Westmead Clinical School at the University of Sydney and Principal Investigator on the trial, said: “As we treat patients with earlier stages of disease and pursue curative intent, quality-of-life considerations definitely affect the choice of treatment. If quality-of-life data support significant clinical benefits, then we may be looking at a new treatment paradigm for these patients.”

Overcoming tumour resistance

More patients taking therapies targeting mutations are experiencing longer periods before their disease worsens; however, tumours often adapt and develop new resistance mechanisms. At WCLC, AstraZeneca is presenting new data on novel combinations that may help overcome a common secondary resistance and established driver of disease progression in patients treated with EGFR TKIs - mesenchymal epithelial transition factor (MET).

Early safety and efficacy results from the multi-arm, Phase Ib TATTON study will be presented, investigating the c-Met receptor tyrosine kinase inhibitor (TKI) savolitinib in combination with EGFR T790M inhibitor Tagrisso (osimertinib) in patients with MET-positive resistance. These data will be supplemented by the first results of a multi-centre Phase Ib study investigating the combination of savolitinib and Iressa (gefitinib) in a similar patient population.

Myung-Ju Ahn, MD, PhD, Professor, Department of Hematology & Oncology, Samsung Medical Center, Seoul, South Korea, said: “Cancer is stealthy and we must continue to find new ways to combat resistance. The early results for both gefitinib and osimertinib in combination with savolitinib show exciting progress and are an important area of continued focus.”

Testing to identify the most suitable treatment

Biomarker-guided lung cancer research is continuing to improve ways to identify patients who are most likely to benefit from treatment with precision medicines. In NSCLC, this has meant improving the accuracy and availability of blood-based testing to facilitate diagnosis and identification of the most suitable treatments throughout the disease continuum. At WCLC, AstraZeneca is presenting progress in ctDNA testing in EGFRm NSCLC across multiple lines of therapy and technologies.

In the 1st-line setting, new analyses across the Tagrisso FLAURA [Abstract #8978] and Iressa BENEFIT trials reveal good concordance between tissue and plasma ctDNA testing, and support the utility of blood-based testing to determine eligibility for both Tagrisso and Iressa. In addition, concordance studies comparing multiple plasma ctDNA diagnostics in two different studies of Tagrisso  in the 2nd line setting continue to build understanding of the comparability of different technologies and expand testing across platforms.

Jhanelle Gray, MD, Medical Oncologist and Director of Clinical Research in the Department of Thoracic Oncology at H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, said: “Testing continues to be a critical part of lung cancer care, but the rapid development and evolution of multiple testing modalities and platforms can be challenging for physician teams to manage. Continued understanding of how assays compare builds confidence in treatment decisions, leading to better patient outcomes”

Combining with IO

As the promise of IO continues to build through the use of monotherapies, the next era in cancer control may involve combinations with a goal of achieving long-term survival for a broader population of patients. At WCLC, AstraZeneca is sharing results from two early trials of checkpoint inhibitor combinations, with and without chemotherapy.

 When combined with chemotherapy, Imfinzi with or without tremelimumab could be administered safely and demonstrated encouraging preliminary clinical activity in patients with NSCLC in a study conducted by the Canadian Cancer Trials Group . The phase II, open-label, NIBIT-MESO-1 study  of Imfinzi plus tremelimumab as 1st- or 2nd-line treatment in patients with malignant mesothelioma demonstrated a safety profile consistent with our previous observations/publications in NSCLC, and clinical activity in this difficult-to-treat cancer.

Rosalyn A. Juergens MD., PhD. assistant professor, Department of Oncology. McMaster University, Canada said: “As we continue to explore the full benefit of immunotherapies, the promise of combinations is really starting to be seen for patients who may not be expected to benefit from the current monotherapies. We continue to push research boundaries in this area with the hope that we can make a real difference to patients in need.”