A 10-year NIH trial found that most people with advanced HLRCC kidney cancer saw their tumors shrink on bevacizumab plus erlotinib. Here’s what the results mean for patients and families.

For years, families living with hereditary leiomyomatosis and renal cell cancer (HLRCC) heard the same hard message: if the kidney cancer spread, there was no treatment proven to work against it. That has changed. In June 2025 the New England Journal of Medicine published the results of a phase 2 trial run at the National Institutes of Health (NIH), and they’re some of the most encouraging news our community has had.

Why HLRCC kidney cancer is different

HLRCC is caused by an inherited change in the FH (fumarate hydratase) gene. People with HLRCC can develop skin and uterine leiomyomas (fibroids) and have a higher risk of a kidney cancer often called FH-deficient renal cell carcinoma. According to the NCI, these tumors can show up in children and young adults and can start to spread even while they’re still very small. That’s why regular kidney imaging matters so much for anyone with an FH variant.

Until this trial, the NCI notes, no drugs were known to be effective against HLRCC-associated kidney cancer.

What the trial tested

The study (ClinicalTrials.gov NCT01130519) ran for about ten years at the NIH Clinical Center. Dr. Ramaprasad Srinivasan of the NCI’s Urologic Oncology Branch led it. It combined two targeted drugs:

• Bevacizumab, an IV medicine that blocks VEGF, a signal tumors use to grow new blood vessels.
• Erlotinib, a daily pill that blocks EGFR, a growth-signaling protein.

The reasoning fits HLRCC’s biology. When the FH enzyme is missing, cells shift how they make energy and turn on signals that drive blood-vessel growth, so cutting off that supply makes sense.

The trial enrolled 43 people with advanced HLRCC-associated papillary kidney cancer and 40 people with sporadic (non-inherited) papillary kidney cancer.

What they found

For people with HLRCC, the results were striking:

• 72% (31 of 43) had a confirmed response, meaning their tumors shrank substantially.
• The median time before the cancer grew again (progression-free survival) was 21.1 months.
• The median overall survival was 44.6 months, almost four years.

The NCI reported that almost all HLRCC participants saw some tumor shrinkage. People with sporadic papillary kidney cancer also benefited: 35% had a confirmed response.

“The median survival now is almost four years with this combination treatment,” said Dr. W. Marston Linehan of the NCI. “This has now become a standard treatment of this disorder worldwide.”

What about side effects?

The side effects were the ones already known for these two drugs. The most common were an acne-like rash (93%), diarrhea (89%) and protein in the urine (78%). The most common serious (grade 3 or higher) side effects were high blood pressure (34%) and protein in the urine (17%). These can be managed, but they need close follow-up with an oncology team that knows the regimen.

What comes next

Researchers aren’t stopping here. Dr. Srinivasan is leading a follow-up phase 2 trial that adds the immunotherapy drug atezolizumab to bevacizumab and erlotinib (NCT04981509). It’s open to adults and to adolescents 12 and older with advanced HLRCC-associated or sporadic papillary kidney cancer. The goal is to find out whether adding immunotherapy leads to more complete responses.

What this means for you

• If you or a family member has advanced HLRCC kidney cancer, ask your oncologist whether bevacizumab plus erlotinib is right for you, and whether a clinical trial might be an option.
• If you carry an FH variant, this is a good reminder that early detection still matters most. Stay on schedule with kidney imaging.
• If HLRCC runs in your family, genetic counseling and testing can help relatives know their risk.

Ten years ago, there was no proven option. Today there’s an established treatment and new trials building on it. That progress came from patients who took part in research, and from the scientists and families who never gave up.

Join us

Connect with patients, caregivers and researchers in our Facebook group, HLRCC Foundation: Knowledge Saves, and help fund awareness and research at hlrcc.org/donate-now.

This article is for education only and isn’t medical advice. Please talk with your own doctor about your care.

Sources

• Srinivasan R, et al. Bevacizumab and Erlotinib in Hereditary and Sporadic Papillary Kidney Cancer. New England Journal of Medicine, 2025.
• NCI Center for Cancer Research. Combining bevacizumab with erlotinib shrinks tumors in patients with rare and aggressive kidney cancer, July 2025.
• ClinicalTrials.gov. NCT01130519: Bevacizumab and Erlotinib in HLRCC or Sporadic Papillary RCC.
• Bravo Montenegro GL, et al. Phase 2 study of bevacizumab, erlotinib, and atezolizumab in HLRCC-associated or sporadic papillary RCC. Journal of Clinical Oncology, 2022 (ASCO abstract TPS4604).