Fred R. Hirsch, MD, PhD
Updated quality-of-life (QoL) data from the PACIFIC trial of patients with locally advanced, unresectable stage III non–small cell lung cancer (NSCLC) will be a highlight of the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer, October 15 to 18, in Yokohama, Japan, according to IASLC CEO Fred R. Hirsch, MD, PhD. Those findings from the trial of PD-L1 inhibitor durvalumab (Imfinzi) will build upon impressive progression-free survival (PFS) results presented in September at the 2017 ESMO Congress.
At ESMO, durvalumab was shown to improve median progression-free survival (PFS) by 11.2 months compared with placebo, which represented the first major advance in decades for patients with stage III lung cancer. The achievement was also the first phase III result for a checkpoint inhibitor in this category, where the standard therapy has been radiation and chemotherapy. “The investigators have submitted additional data, including QoL data,” which will augment a heavy focus this year on immunotherapy at the conference, which is expected to attract 6000 lung cancer specialists, Hirsch said.
“We will have updates from the big clinical trials, we will have new scientific information which has not yet materialized in clinical trials but will in the near future, and we will have updates on what’s going on in the prevention and early detection area,” he said. “We will have a lot of discussion and new data on immunotherapy from several studies, but because we are moving immunotherapy to earlier-stage treatment, that will certainly be discussed.” In that category, he said some “very promising” results will be presented from a subgroup study of patients involving use of NTRK
-inhibitor entrectinib. In addition, some potentially game-changing data on treating mesothelioma will be offered, among the close to 2000 presentations at the conference.
Supplemental data will also be presented on the FLAURA trial, which evaluated frontline osimertinib (Tagrisso) versus standard therapy for patients with EGFR
-mutant NSCLC. Phase III data were presented at ESMO showing a median PFS of 18.9 months, representing a 54% reduction in the risk of progression or death compared with standard therapy. Lead investigator Suresh Ramalingam, MD, has described osimertinib as having set a new standard of care in the frontline setting, and Hirsch added that the drug has clearly displaced first and second-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib (Iressa) and erlotinib (Tarceva).
“When patients progress on first or second-generation therapy they develop the T790M
mutation, and in this case osimertinib is very effective—we know that—and it is also effective for patients who develop brain or central nervous system spread from the disease, which is common, and first- and second-generation EGFR
TKI is not very effective in the brain, but osimertinib has more effective penetration. That was the status for osimertinib until very recently,” said Hirsch. “In the FLAURA study, they looked at whether osimertinib could be used in the first line and eventually be replaced by erlotinib and gefitinib, and the data presented at ESMO showed clear benefits from osimertinib versus standard of care.”
Based on the findings from the FLAURA study, AstraZeneca, the company developing osimertinib, has already entered approval discussions with relevant health authorities.
Biomarker studies are another focus of the IASLC conference, with plasma determination of molecular features a standout in terms of interest-generating potential and the number of studies concentrating on that area alone, Hirsch said.
Findings from the Blueprint PD-L1 IHC Assay Comparison Project, where several assays were compared to guide clinicians in better understanding their utility, also will be presented, he noted. The diversity of products, tremendous competition among producers of the tests, and variability of results and applications exacerbates the difficulty clinicians have in deciding which to use and how to interpret their results, Hirsch said.
The Blueprint project is an industrial-academic collaborative partnership, which on that basis alone “is an achievement,” he said. Both pharmaceutical representatives and diagnostic company representatives are involved. “IASLC has succeeded in bringing them together and working with them to compare the different assays and see if they can be harmonized, and that project has gotten enormous attention not only in the scientific and clinical communities but also from regulatory bodies.”