Australian highlights from AACR 2020

By Michael Woodhead

29 Apr 2020

Australian researchers have featured prominently in presentations of study results made at the virtual meeting of the American Association for Cancer Research (AACR) this week.

The meeting, which was originally scheduled to take place in San Diego, heard from Australian researchers involved in new therapies for advanced melanoma (IMspire150), aspirin prevention of metastases  as well as from Australian sites for therapies in advanced BRCA-mutated breast cancer (EMBRACA).

Professor Grant McArthur from the Peter MacCallum Cancer Centre in Melbourne, presented results in the opening plenary showing that in patients with BRAF V600-mutated melanoma the addition of atezolizumab to  cobimetinib and vemurafenib decreased the risk of progression free survival (15.1 vs. 10.6 months) versus placebo and a combination of the latter two drugs. The median duration of response was also prolonged in the atezolizumab arm (21.o vs. 12.6 months), but objective response rates were similar in both groups.

The study enrolled 514 patients with unresectable stage IIIc/IV melanoma  and BRAFV600 mutations who were followed for a median of 18.9 months

“Patients with advanced BRAF mutant melanoma can be treated with combinations of BRAF and MEK inhibitors … that offer the advantage of high response rates. However, unfortunately for many patients, these responses are short-lived. Immune checkpoint inhibitors, in contrast provide more durable responses but have a lower response rate,” said Professor McArthur.

The researchers concluded that “combination therapy with atezolizumab, cobimetinib and vemurafenib was tolerable and manageable, produced durable responses, and … represents a viable treatment option for BRAFV600 mutation-positive advanced melanoma.”

Also presented at AACR were new data from the Phase III EMBRACA trial, showing that the PARP inhibitor talazoparib did not demonstrate a statistically significant overall survival (OS) benefit for patients with metastatic HER2-negative breast cancer and mutations in the BRCA1/2 genes.

The trial, which included Australian centres at the Mater Research Institute and the University of Queensland, and the Concord Repatriation General Hospital, Sydney, had previously reported results showing that talazoparib significantly prolonged progression-free survival vs physician’s choice of chemotherapy (hazard ratio 0.54) and improved patient-reported outcomes.

After 412 patients were followed-up  (44.9 months for the talazoparib group and 36.8 months for the chemotherapy group), the Hazard Ratio for OS was 0.85 (95% CI 0.67-1.07; P = 0.17).

The study investigators said interpretation of the overall survival results may have been confounded by subsequent treatments, noting that about one-third of patients in the chemotherapy group received a subsequent PARP inhibitor, compared with only 4.5% of patients who received talazoparib.

Meanwhile researchers from the QIMR Berghofer Institute in Queensland presented results showing that aspirin reduces the incidence of metastasis seven fold in a preclinical study of Braf mutant colorectal cancer.

Using a dose of aspirin equivalent dose of 80-120mg per day, they found no reduction in carcinoma incidence (31% vs 28% for placebo vs aspirin) over 14 months but a significantly lower incidence of metastases (35% vs 5%, P = 0.0134).

The researchers said the findings suggested that aspirin may have potential for reducing recurrence and mortality in colorectal cancer.

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