The Bottom Line

Locally advanced basal cell carcinoma (BCC) is a large or deep skin cancer that cannot be removed with surgery without causing serious harm. Two medications — vismodegib (Erivedge) and sonidegib (Odomzo) — target a genetic switch that drives most BCCs and can shrink tumors by 40–65%. They work well, but side effects like muscle cramps and taste changes lead many patients to stop treatment. These drugs do not cure BCC permanently — tumors regrow if you stop taking them — but they can shrink cancer enough to make surgery possible, or keep it under control long term.

What Is Locally Advanced Basal Cell Carcinoma?

Basal cell carcinoma (BCC) is the most common skin cancer. Most BCCs are small and removed easily with surgery. But some grow very large, grow back after treatment, or invade deep structures like bone, cartilage, or tissue near the eye or brain. These are called locally advanced BCCs (LA-BCC).

LA-BCC cannot be removed without taking away too much tissue — which could mean losing an eye, ear, or large portion of the face. Radiation is sometimes used, but for many patients neither surgery nor radiation alone is a good option. That is where hedgehog pathway inhibitors come in.

What Is the Hedgehog Pathway — and Why Does It Matter?

Around 80–90% of BCCs carry mutations in genes that control a signaling system called the hedgehog pathway. Normally, this pathway is switched off in adult skin. In BCC, mutations (most commonly in a gene called PTCH1) flip the switch permanently on, causing cancer cells to keep growing and dividing.

Vismodegib and sonidegib block a key protein in this pathway called smoothened (SMO). When SMO is blocked, the runaway growth signal is turned off and the tumor shrinks.

The Two Available Medications

Vismodegib (Erivedge) — 150 mg once daily by mouth: In clinical trials, vismodegib shrank tumors (partial or complete response) in 40–50% of locally advanced BCCs. About 10–15% of patients had a complete response (no detectable cancer). Tumors typically start shrinking within 4–6 months of starting treatment.

Sonidegib (Odomzo) — 200 mg once daily by mouth: Sonidegib shows somewhat higher response rates of 55–65% for LA-BCC, with complete responses in 15–20% of patients. Some doctors believe sonidegib may be slightly more potent, though no head-to-head trial has directly compared the two drugs.

Both medications are taken as daily pills. You do not need an IV or injections.

What Are the Side Effects?

These drugs have a well-known set of side effects. Knowing what to expect helps you manage them:

  • Muscle cramps (60–70% of patients): The most common problem. Cramps usually affect the legs and can range from mild to severe. About 30–40% of patients stop the medication because of this. Stretching, magnesium or calcium supplements, and staying hydrated can help.
  • Taste changes (40–50%): Food may taste bitter, metallic, or bland throughout treatment. This can reduce appetite and affect nutrition.
  • Hair loss (20–30%): Hair thinning or loss usually begins in the first 1–3 months but grows back 1–3 months after stopping the drug.
  • Weight loss (15–20%): Often related to taste changes and reduced appetite.
  • High triglycerides (10–15%): Blood fat levels may rise. Your doctor will monitor this with blood tests.
  • Fatigue and nausea: Common but usually manageable.

Important warning for pregnancy: These drugs cause serious birth defects and must never be taken during pregnancy. Women of childbearing age must use reliable contraception during treatment and for a period after stopping.

How Long Do Responses Last?

Responses last as long as you keep taking the medication. The median time before the tumor starts growing again is around 7–9 months in clinical trials, but about 25–30% of patients have responses that last beyond 2 years. If you stop the medication, the tumor almost always starts regrowing within weeks to months.

About 25–30% of patients whose tumors initially responded will eventually develop resistance — the drug stops working. This can happen through new mutations in the SMO gene or through other growth pathways activating. Sometimes switching from one drug to the other helps briefly, but durable responses to sequential therapy are uncommon.

Using These Drugs Before Surgery (Neoadjuvant Therapy)

One powerful strategy is taking vismodegib or sonidegib for 3–12 months before surgery. This can shrink a tumor that was too large to remove into something that is now surgically manageable. Studies show that 40–50% of patients achieve 50% or more tumor shrinkage with this approach. A small number (5–20%) have no detectable tumor remaining at surgery.

Surgery after neoadjuvant hedgehog inhibitor therapy has lower recurrence rates than surgery alone or drug therapy alone — combining approaches gives the best results.

Special Case: Gorlin Syndrome

Gorlin syndrome is a rare inherited condition where people develop dozens or even hundreds of BCCs throughout their lifetime. Vismodegib dramatically reduces new BCC formation in these patients — by 50–75% compared to untreated rates. This can spare patients from needing dozens of surgeries. However, stopping the drug leads to a rapid rebound of new tumors.

When to See a Dermatologist

  • You have a BCC that has come back after surgery or radiation
  • Your BCC is very large (several centimeters), near the eye, ear, nose, or on the scalp
  • Your doctor has told you the tumor cannot be fully removed without major surgery
  • You have been diagnosed with Gorlin syndrome and have multiple BCCs
  • You are on vismodegib or sonidegib and experiencing severe side effects
  • Your tumor starts growing again while on treatment

Frequently Asked Questions

Will I need to take these pills forever?

It depends on your goals. If the drug is controlling your cancer long term (and surgery is not planned), you may need to take it indefinitely or until the drug stops working. If the plan is to shrink the tumor so surgery becomes possible, you will typically take the drug for 3–12 months, then have surgery. After surgery, some doctors recommend continuing the pill for 12–24 months to reduce recurrence risk.

What happens if the drug stops working?

If resistance develops, your doctor will discuss alternatives — possibly switching to the other hedgehog inhibitor, radiation therapy, immunotherapy (cemiplimab), or conventional surgery if the tumor is now resectable. Newer combinations with other targeted drugs are being studied in clinical trials.

Are there other drug options for BCC that doesn't respond to hedgehog inhibitors?

Yes. Cemiplimab (Libtayo), a PD-1 immune checkpoint inhibitor, is FDA-approved for advanced BCC that progresses on or cannot tolerate hedgehog inhibitor therapy. It works by activating your immune system to fight the cancer.

Can I take breaks from the medication to manage side effects?

Yes — intermittent dosing (taking planned breaks) is sometimes used to reduce side effects while preserving tumor control. Studies suggest that intermittent scheduling can improve tolerability, though continuous dosing generally produces better tumor control. Discuss a schedule with your dermatologist or oncologist.

References

  1. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179.
  2. Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015;16(6):716-728.
  3. Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol. 2014;70(1):60-69.
  4. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366(23):2180-2188.
  5. Dummer R, Guminski A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study. Br J Dermatol. 2020;182(6):1369-1378.

Trusted Resources

Always consult a board-certified dermatologist or dermatologic oncologist about your specific skin cancer diagnosis and treatment options. This information is for educational purposes only and does not replace professional medical advice.