A precision oncology Pfizer drug now has clinical data showing it helped patients with colorectal cancer live longer, results that study investigators say could change the way physicians treat those whose disease exhibits the specific genetic signature targeted by this therapy.
Patients who received the Pfizer drug Braftovi alongside standard of care colorectal cancer therapies had a 51% lower risk of dying than patients treated with the standard of care chemotherapy. These Phase 3 results were both statistically significant and clinically meaningful, Dr. Elena Elez, head of the colorectal cancer group at Vall d’Hebron Institute of Oncology in Barcelona and co-principal investigator of the study, said during a briefing with journalists earlier this week. The data are scheduled for presentation Friday afternoon during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The trial results have also been published in the New England Journal of Medicine.
Braftovi is a kinase inhibitor, a small molecule designed to inhibit enzymes that, when mutated, drive cancer growth. This Pfizer drug is specifically designed to block enzymes with a mutation called BRAF V600E. It was first approved in 2018 for treating advanced melanoma with that genetic signature.
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Late last year, the FDA expanded Braftovi’s label to include first-line treatment of colorectal cancer with the BRAF V600E mutation. That accelerated approval was based on Phase 3 results showing a 61% objective response rate. Progression-free survival and overall survival in this trial are the confirmatory benchmarks that could support full FDA approval in this indication. Positive preliminary results were released in February. The ASCO presentation will provide specific figures.
The Phase 3 study tested Braftovi alongside cetuximab (brand name Erbitux), an Eli Lilly drug that is a standard treatment for colorectal cancer when used alongside chemotherapies. Lilly’s drug is an antibody that blocks a cancer target called EGFR. The pairing of the Pfizer and Lilly drugs was tested with and without standard chemotherapy and compared to standard of care chemotherapy, administered with or without the Roche cancer drug Avastin.
Patients in the Braftovi, Erbitux, and chemo arm lived longer without their cancer worsening. This progression-free survival was 12.8 months in the study drug arm compared to 7.1 months for the control group. But progression-free survival does not always correlate with improvement in overall survival. Elez noted that Braftovi’s results showed a median overall survival of 30.3 months compared to 15.1 months in the control arm.
“This survival data is unprecedented given the historically poorer prognosis in BRAF-mutated metastatic colorectal cancer,” Elez said.
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The most common side effects for the patients treated with the Pfizer and Lilly drugs plus chemo included nausea, anemia, and diarrhea. Elez said these effects were consistent with the known profile of the drugs separately and were manageable. She added that Pfizer’s Braftovi, alongside Erbitux and standard chemo, could become a practice-changing new standard of care for patients whose colorectal cancer carries the BRAF V600E mutation.
In the same briefing with journalists, ASCO expert Dr. Joel Saltzman described the trial results as another victory in the march toward precision oncology. Only about 10% of colorectal cancer patients have the mutation addressed by Braftovi, but the dramatic improvement in response rate and overall survival will likely translate into improved quality of life for them, he said. Saltzman added that the study emphasizes the importance of upfront biomarker testing to identify the best treatment, an approach that’s already playing out in other indications.
“When we look at patients now with colorectal cancer, we don’t look at them as having one disease,” said Saltzman, a Cleveland Clinic medical oncologist. “With biomarker testing, we now have three distinct diseases that it’s important to even know about — their BRAF status their RAS mutation status, and their microsatellite stable status — to help decide a rational treatment choice moving forward.”
Braftovi came from Pfizer’s 2019 acquisition of Array Biopharma. Besides its approved uses in melanoma and colorectal cancer, the drug is approved for treating advanced cases of non-small cell lung cancer carrying the BRAF V600E mutation. For 2024, Pfizer reported $607 million in sales for the product across all of its approved indications, a more than 27% increase over sales in the prior year.
[Update: The following two paragraphs added with analyst comments.] In a note sent to investors, Leerink Partners analyst David Risinger described the overall survival benefit as “surprisingly compelling.” But he noted that Braftovi-treated patients experienced more adverse events compared to those who received the standard of care, particularly reports of anemia. That said, Leerink believes the overall survival benefit more than offsets the safety concerns and could help the drug achieve blockbuster status.
“Overall, we believe the data support the Braftovi combination regimen as the new standard of care,” Risinger said.
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