Pfizer isn’t stopping to smell the roses on its speed run to secure a full FDA approval for its Braftovi combination therapy. After securing a unique accelerated approval not quite six months ago, the company has now posted a phase 3 win that it hopes will support a conversation to full approval this year.
The combo sees Braftovi paired with Eli Lilly’s Erbitux and the chemo regimen mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) to treat patients with untreated metastatic colorectal cancer (mCRC) who have a BRAF V600E mutation. In the latest reveal from Pfizer’s phase 3 Breakwater study, presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting, the Braftovi combination slashed the risk of death by 51% compared with standard-of-care chemotherapy, with or without Roche’s Avastin.
More specifically, patients who took the Braftovi regimen lived for a median of 30.3 months, more than doubling the 15.1 months for those who received chemotherapy, with or without Avastin. The Pfizer combo also provided a significant difference in how long patients lived without their disease getting worse. On that metric, the Braftovi group experienced a median 12.8 months of progression-free survival, compared with the 7.1 months seen in the control arm.
To put it simply, the Breakwater results are “the first promising survival outcomes ever reported for BRAF-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough,” co-principal trial investigator Elena Élez, M.D., Ph.D., said in a Pfizer release.
Previously, an interim analysis showed a preliminary 53% lower risk of death for the Braftovi regimen compared with standard of care, although that finding was not statistically significant at the time. The fresh overall survival results come from a second interim analysis, further confirming the benefit of the regimen.
While it only applies to a small patient population, the win is especially significant considering the high risk of death associated with the mutated cancer type. Colorectal cancer is the third most common cancer type globally and the second leading cause of cancer-related death, although BRAF mutations are estimated to impact a smaller group of about 8% to 12% of those with mCRC. BRAF V600 specifically is the most common BRAF mutation and can double the risk of mortality compared with patients who have no such BRAF mutation, according to Pfizer.
Before the FDA cleared the Braftovi treatment regimen in December, no biomarker-driven therapies were specifically approved for the first-line treatment of those diagnosed with the mutated cancer.
That December approval was an accelerated nod and marked one of the first under the FDA’s Project FrontRunner, a program meant to encourage the development of new cancer drugs for earlier lines of treatment. Under the framework, Pfizer was able to use a surrogate endpoint from the Breakwater study to pick up the accelerated approval while continuing the trial toward a more mature readout that could support a full approval.
Pfizer is currently discussing the data with the FDA to support potential conversion to a full approval this year, the company said.
The “unprecedented” results could serve to “further establish the benefit of the Braftovi combination regimen and its potential to become a new standard-of-care,” Pfizer's chief oncology development officer, Johanna Bendell, M.D., commented in the company's press release.
In a broader sense, the Breakwater trial represents “yet another victory in the march toward precision oncology,” Joel Saltzman, M.D., an ASCO expert in gastrointestinal cancers, pointed out in a press briefing on the data.
“This study further emphasizes the importance of upfront biomarker testing to find the best available therapies to proceed with our patients in colorectal cancer,” Saltzman noted. “This is a story we've seen across many diseases, and it's certainly a pleasure to see this play out in the colorectal population.”