Array, Pierre Fabre bowel cancer therapy ‘could replace chemo’

A new trial has shown for the first time that a combination of three targeted therapies can improve survival in patients with advanced colorectal cancer with a specific mutation.

The three-drug regimen – based on Array BioPharma/Pierre Fabre’s BRAF inhibitor Braftovi (encorafenib) and MEK inhibitor Mektovi (binimetinib) along with Eli Lilly’s EGFR-targeted antibody Erbitux (cetuximab) – almost doubled overall survival in patients with BRAF-positive colorectal cancer in the BEACON trial.

The data suggest that the three-drug combination should replace chemotherapy for one in seven patients with metastatic colorectal cancer who have a BRAF mutation, according to lead investigator Scott Kopetz of MD Anderson Cancer Centre in the US, who presented the study at the ESMO World Congress on Gastrointestinal Cancer 2019 over the weekend.

The results should also give Pierre Fabre and Array’s two drugs a leg-up in the market for BRAF/MEK inhibitors, where they face stiff competition from Novartis and Roche, as BEACON is the first and only phase 3 trial to test BRAF/MEK combinations in this patient group.

The combination resulted in a median overall survival (OS) of 9 months for the combination therapy compared to 5.4 months for chemotherapy plus Erbitux, the current standard-of-care treatment, with an overall response rate of 26.1% versus 1.9%, respectively. Progression free-survival (PFS) was 4.3 months compared to 1.5 months.

The trial enrolled patients who had previously been treated with one or two lines of therapy and who are known to have a particularly poor prognosis. Two-drug therapy with Braftovi and Erbitux also performed well, with an OS of 8.4 months.

Kopetz tweeted that the response rates in second-line patients was 34% for the triplet, 22% for the doublet and just 2% with chemotherapy.

“Colorectal cancer does not respond to BRAF therapy alone because tumour cells adapt through other mechanisms after initial treatment,” he said. “With this triple targeted therapy, we are using a very scientifically logical combination to inhibit BRAF and these other mechanisms.”

Pierre Fabre licensed rights to Braftovi and Mektovi from Array in 2015 for $30 million upfront and up to $425 million in milestone payments.

The duo is already approved to treat BRAF-mutated melanoma, and almost doubled survival compared to Roche’s BRAF inhibitor Zelboraf (vemurafenib) in a pivotal trial in that indication.

Novartis’ MEK/BRAF inhibitor duo Mekinist (trametinib) and Tafinlar (dabrafenib) is now the main competitor to the two drugs, however, growing 31% to $1.12 billion in sales last year. Approval in colorectal cancer would give Array and Pierre Fabre space to grow without direct competition.

The BEACON data is also welcome news for Pfizer, which just agreed to buy Array in an $11.4 billion deal due to complete later this year.

“This targeted therapy combination should be a new standard of care for this patient group,” said Kopetz.

“Further investigation is needed to determine if this combination may also benefit those with less advanced disease or as a first-line treatment.”

A study called ANCHOR-CRC is already ongoing, testing the effects of triplet therapy in previously-untreated patients with metastatic BRAF-mutated colorectal cancer.

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