ASCO: Updated targeted therapy clinical trials results continue to show improved outcomes for advanced colorectal and bladder cancers

Updated results from two MD Anderson clinical trials presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting indicate improved outcomes for cancer patients with specific gene mutations when treated with targeted therapies. Targeted therapies from both the BEACON CRC and the BLC2001 clinical trials resulted in FDA approvals of treatments for subsets of patients with advanced colorectal and bladder cancers.

Encorafenib plus cetuximab with or without binimetinib for BRAF V600E metastatic colorectal cancer: Updated survival results from a randomized, three-arm, Phase III study versus choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC) (abstract 4001)

Updated results of the BEACON CRC Phase III clinical trial indicate that the treatment regimen of encorafenib plus cetuximab had similar outcomes to the study’s three-drug combination of encorafenib, cetuximab and binimetinib in patients with BRAF-mutated metastatic colorectal cancer (mCRC).

Both regimens are well-tolerated and are shown to significantly improve patients’ overall survival, overall response rate and progression-free survival. While additional research is needed into the potential added benefits of using the triplet therapy with binimetinib, exploratory analysis indicates that some patient populations may benefit from the addition.

Last month, encorafenib plus cetuximab earned FDA approval as a treatment for adult patients with mCRC and the BRAF V600E mutation. BEACON CRC is the first and only Phase III clinical trial designed to test combination targeted therapies in patients with mCRC and the BRAF V600E mutation, which occurs in 10% to 15% of mCRC patients and is marked with poor prognosis.

Standard of care treatment has a median overall survival of 5.4 months, whereas both the doublet and triplet therapies improved median overall survival rates to 9.3 months. Additionally, overall response rate was 20% for encorafenib plus cetuximab and 27% for the triplet regimen including binimetinib, compared to just 2% for standard therapy.

“The encorafenib plus cetuximab regimen should be the new standard of care in most patients with previously treated BRAF V600E-mutant mCRC,” says principal investigator Scott Kopetz, M.D., associate professor of Gastrointestinal Medical Oncology. “This regimen may also serve as a suitable backbone to evaluate the addition of other targeted agents and/or chemotherapy.”

ERDAFITINIB in locally advanced or metastatic urothelial carcinoma (mUC): Long-term outcomes in BLC2001 (abstract 5015)

After a median two-year follow-up of the BLC2001 Phase II clinical trial, treatment with the oral FGFR inhibitor erdafitinib (ERDA) showed consistent efficacy among patients with locally advanced or metastatic urothelial cancers and FGFR gene mutations.

The study was a breakthrough for patients with mutations in the FGFR3 gene, which are present in approximately 15% to 20% of patients with metastatic bladder cancer.  

For decades, the standard treatment for these cancers has been an aggressive regimen of cisplatin-based chemotherapy — an intensely powerful medication that comes with significant side effects. In recent years, new checkpoint blockade inhibitors have been approved, however, the response to these immunotherapies is only about 15% to 20%.

At a median two-year follow-up, the therapy showed a median OS of 11.3 months and an objective tumor response rate of 40%. Additionally, 12- and 24-month survival rates were 49% and 31%, respectively, with 31% of patients having responses longer than one year.

Treatment with ERDA, which last year became the first FDA-approved targeted therapy for patients with metastatic bladder cancer, has been well-tolerated and can offer patients a new option after previous treatments have failed to work or could no longer be tolerated. ERDA appeared effective in a subset of patients for whom immunotherapy had previously failed.

“With the approval of erdafitinib, the first-in-class FGFR3 inhibitor, we can now consider personalized therapy for the treatment of our urothelial cancer patients,” says principal investigator Arlene Siefker-Radtke, M.D., professor of Genitourinary Medical Oncology. “We are now exploring whether an FGFR3 altered urothelial cancer benefits more from erdafitinib or a checkpoint inhibitor in the Phase III trial, THOR, and combining erdafitinib with a checkpoint inhibitor in the randomized trial NORSE to better treat our FGFR3 altered urothelial cancer patients.”

Full information on co-authors and disclosures for these studies is available here and here.