Effective drug for bowel cancer subset within reach

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The one in ten patients with colorectal cancer who have the BRAF mutation may benefit from a recent PBAC recommendation to list encorafenib on the PBS.

The one in ten patients with colorectal cancer who have the BRAF mutation may benefit from a recent PBAC recommendation to list encorafenib on the PBS. 

The Pharmaceutical Benefits Advisory Committee (PBAC) has recommended that encorafenib (Braftovi) in combination with cetuximab be listed on the PBS for patients with metastatic colorectal cancer who have the BRAF V600E-variant.

Patients with this variant have a poor prognosis, with the average survival being just four to six months after failure of initial therapy. In Australia, approximately 10% of metastatic colorectal cancer patients carry the BRAF V600E mutation.

At its May meeting, PBAC acknowledged the high clinical need, considered that the clinical benefit was meaningful, and decided the drug would be cost-effective.

Clinical trials have shown that people taking encorafenib (which targets the faulty BRAF protein) and cetuximab (which targets a second protein known as EGFR) lived nine months on average, compared to 5.4 months for those taking one or two different combinations of chemotherapy and cetuximab.

The BEACON study of 665 patients published in NEJM in 2019 found that a combination of encorafenib, cetuximab, and binimetinib resulted in significantly longer overall survival and a higher response rate than standard therapy in this patient group.

Associate Professor Jeanne Tie, an oncologist who leads colorectal cancer trials at the Peter MacCallum Cancer Centre and worked on BEACON, said it was great to hear that encorafenib will be coming through the PBS.

Encorafenib increases life expectancy by targeting an abnormal protein but it costs around $6,000 per month for patients to self-fund the treatment so PBS funding would benefit patients, she said.

Associate Professor Jayesh Desai, a medical oncologist and the associate director of clinical research at the Peter MacCallum Cancer Centre (and who was one of the lead principal investigators and co-author of the BEACON trial), said this was “an important step forward after many frustrating failures”.

“I’ve been working on this for a decade! From using the first BRAF targeting agents in trials, to multiple combination approaches,” he said. 

Although only 10% of patients with colorectal cancer had the BRAF mutation, this group was important because these cancers were particularly aggressive and deadly, he said.

“Targeting BRAF has been challenging, as the biology of BRAF mutations in colorectal cancer is somewhat unique, requiring a combination approach (with an EGFR inhibitor) to overcome a resistance mechanism that develops almost instantly,” he said.

“The BEACON trial, which we published in the NEJM, and the PBAC submission was based on; demonstrated a clear benefit in using a dual-agent BRAF targeting approach, and based on this, has now been approved in multiple regions around the world.

“In a broader sense, this represents the first successful molecularly targeted approach to targeting a specific gene in colorectal cancer,” he said.

Another clinical trial underway called BREAKWATER, has recently opened in Australia at a number of sites including Peter MacCallum.

Professor Desai, who is one of the global lead investigators, and Associate Professor Tie, will investigate whether encorafenib can improve survival in the first-line setting, given before chemotherapy in patients with BRAF V600E–mutated metastatic colorectal cancer. 

{PBAC currently only recommends encorafenib after chemotherapy, as it is basing its decision on the BEACON trial.)

Patients with the BRAF V600E mutation have seen little improvement in survival in recent years, despite overall improvements in bowel cancer survival, according to Bowel Cancer Australia. 

Bowel Cancer Australia pointed to the story of Tuula Torenius, a patient with this subtype of the disease, as a case study.

Tuula Torenius’ story

I was diagnosed with bowel cancer just over seven years ago. After the initial hemicolectomy and five months of chemotherapy, I was able to lead a fairly normal life. I was retiring age (67) at the time, so I left work and started to do some voluntary work a few days a week and generally enjoying a pretty much normal life.

Metastatic bowel cancer came back as a Krukenberg tumour on my ovary, so I had further surgery to have my ovaries removed. I did not have any treatment after that until it came back again in my peritoneum. I had chemo and immunotherapy (Avastin) for about 12 months.

Peter Mac was having a trial on Braftovi and Mektovi and I was considered for the trial but did not meet all the criteria. When the trial was over about October 2019, I was able to self-fund the Braftovi tablets. I was taking Braftovi capsules daily in conjunction with Cetuximab every two weeks, via IV beginning in November 2019, and it controlled my metastatic stage 4 bowel cancer. I have a lot of family and friends and don’t have time to be sick.

Fortunately, Braftovi gave me all I could hope for. I had very few side effects, and it was much kinder on my body than the chemotherapies I have endured. Until recently, the cancer was controlled, I didn’t have any pain and I could lead a pretty normal life.

I obtained the information for Braftovi from my oncologist. As this drug is fairly new and expensive, I don’t know any other people who are taking it. I wish this drug was more accessible to all the people with bowel cancer that have the BRAF mutation. I really hope it becomes more readily available.

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