AstraZeneca ahead of competition with immunotherapy at early disease stage - oncology head

by Belén Diego
MADRID, Sept 12 (APM) - Jamie Freedman, AstraZeneca's head of oncology, has said the firm's efforts to bring immunotherapy to early disease stages will allow a broader patient population to be treated and will establish the company as a leader in lung cancer.
Speaking to APM on the sidelines of the meeting of the European Society for Medical Oncology (ESMO) in Madrid this weekend, Freedman said early disease stage is an area in which AstraZeneca is ahead, with most companies focusing mainly on advanced cancer.
Freedman said AstraZeneca's primary growth drivers are Tagrisso (osimertinib), Lynparza (olaparib), Imfinzi (durvalumab) and acalabrutinib.
Results of the FLAURA trial, presented at ESMO, show Tagrisso improves progression-free survival in comparison with tyrosine kinase inhibitors Iressa and Roche's Tarceva (erlotinib), currently used in first-line treatment of EGFR-mutated non-small cell lung cancer (NSCLC). (APMHE 54632)
"Tagrisso is the only EGFR inhibitor that would treat resistance via T790M. We always thought that Tagrisso could be better than Iressa and Tarceva in first line for three reasons: it can prevent the emergence of the resistance, so administering Tagrisso upfront you can treat the entire population, even patients who progress very rapidly; another important point is that this is the only EGFR inhibitor that crosses the blood-brain barrier and can treat brain metastases, the main cause of death in lung cancer; the third point is that the safety and tolerability profile is better than that of Iressa and Tarceva," he said.
According to Freedman, it is particularly important to note that the curves representing overall survival (OS) in the trial's arms show a clear separation quite early, so the drug's results in this endpoint are heading in the direction of a big difference. This will need to be confirmed on a bigger population than that of the FLAURA trial, he cautioned.
Based on the separation of the survival curves, there is no reason not to administer Tagrisso in first line in EGFR mutated cases, he added. Freedman thinks the sales potential of Tagrisso is "tremendous", because it will become the first-line therapy of choice for EGFR mutations, displacing Iressa and Tarceva.
The company is also looking into drug combinations which will help overcome resistance.

Lynparza, a pipeline in a product

"Lynparza is what we call a pipeline in a product, it has so many tumour indications based on the BRCA mutation, which is a very clear selection marker and is prevalent across a number of tumour types," he said.
AstraZeneca is also exploring the combination of the drug with VEGF inhibitors to reach a broader patient population, he noted.
Freedman highlighted acalabrutinib as another exciting product in the company's pipeline. This drug was granted breakthrough status by the U.S. Food and Drug Administration (FDA) in patients with mantle cell lymphoma (MCL) at the beginning of August, the second such status in a week for the UK-based pharma after one for Imfinzi in non-small cell lung cancer (NSCLC). (APMHE 54142)

Practice-changing trials

At ESMO, AstraZeneca presented the results of two trials which Freedman called "practice-changing" - FLAURA and PACIFIC. This echoed a Tuesday statement from ESMO which included a list of practice-changing studies presented in Madrid, with the PACIFIC trial of Imfinzi at the top of the list as the basis for a "new standard of care for locally advanced, unresectable stage III NSCLC".
Freedman said Imfinzi offers a new option for roughly 30% of lung cancer patients, the majority of whom are not eligible for curative surgery. With no new products beyond chemotherapy or radiation for well over a decade, 89% of patients progress within one year.
"We embarked on this trial on the premise that if you have early-stage disease your immune system is more intact and the chances that immunotherapy works are better," he said.
He noted that none of AstraZeneca's competitors thought about using immunotherapies this way, because the traditional approach is to start with the most advanced cases, in metastatic disease. "This is counterproductive in immunology, because in more advanced patients the immune system is suppressed," he said.
According to Freedman, it is particularly interesting that in the PACIFIC trial of Imfinzi (already approved for bladder cancer), although a better response was recorded in patients with high levels of PDL-1 expression, all patients regardless of PDL-1 status were included and benefited from the drug, "including EGFR+ tumours, suggesting this is going to be a drug for all patients.
"If you have high PDL-1 expression in advanced disease, patients will probably respond better. However, PDL-1 is probably not the best biomarker for patient selection. It is not such a good predictor in the sense that patients with low PDL-1 expression can benefit from the drug. The industry is looking for better molecular profiles," he said. Interferon gamma and tumour mutational burden (TMB) are examples of potential biomarkers. Even though exploratory, these are thought to be better predictors of responsiveness, he said.
"The PACIFIC trial opens up numerous opportunities in early-stage disease, in lung cancer as well as other tumours", Freedman added.

Even earlier disease stages

Freedman said AstraZeneca is looking into use of Imfinzi as adjuvant therapy after lung cancer surgery.
He said it is important to bear in mind that patients with early-stage disease are reasonably healthy, so they should receive a therapy that is well tolerated - and Imfinzi is "extraordinarily" well tolerated.



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