You’re Not Out of Options—What To Do After First Line Therapy Fails

Published:  
10/07/2025
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Hearing that your treatment for melanoma has stopped working—or that you’ve had to stop because of side effects—can be overwhelming. It’s natural to feel discouraged. But as this recent webinar reminds us, there are still many paths forward.

Hosted by Melissa Wilson, PA-C, and featuring Allison Betof, MD, PhD, Associate Professor of Medicine and Oncology and Director of the Melanoma Program at Stanford University, the conversation offers both hope and clarity about what comes next when first-line therapy fails.


When “Failure” Doesn’t Mean the End

Dr. Betof begins by helping us rethink what it really means when therapy “fails.” Sometimes treatment ends not because the cancer is growing, but because side effects become too difficult to manage. In those cases, it can actually be appropriate to pause and watch—the immune system may continue to hold the cancer in check even after treatment has stopped.

If scans show that the disease is growing, that’s a different story—but still not the end. It simply means it’s time to look at the next best option for your unique situation.

What Helps Guide the Next Step

Imaging tests like CT, PET, or MRI scans remain the most reliable tools for assessing what’s happening inside the body. Blood markers such as LDH or circulating tumor DNA (ctDNA) are being researched, but they’re not yet reliable enough to guide treatment changes.

Before moving forward, Dr. Betof recommends making sure your melanoma has undergone next-generation sequencing (NGS). This type of genetic testing looks for specific mutations—such as BRAF, NRAS, or KIT—that might open the door to new targeted therapies or clinical trials.

Hope in New Therapies and Trials

One of the most promising developments for people with advanced melanoma is cell therapy, particularly tumor-infiltrating lymphocyte (TIL) therapy. For eligible patients, getting referred to a cell therapy center early—especially after progression on checkpoint inhibitors—may offer a better chance at response.

Dr. Betof also clears up some common misconceptions:

  • Having brain metastases or multiple prior treatments doesn’t necessarily rule you out of trials.
  • Participating in a cell therapy trial doesn’t mean you’ve run out of future options.

There are always more avenues to explore, and new research is emerging all the time.

Finding Support Along the Way

Moving into a new phase of treatment can be emotionally and logistically challenging. That’s why Dr. Betof emphasizes the importance of support networks. Organizations like AIM at Melanoma and the American Cancer Society can help with travel resources, trial navigation, and connecting to specialists or second opinions.

And while medical treatment is key, lifestyle support matters too—gentle movement, nourishing foods, and emotional well-being all play a role in helping your body and spirit stay strong through the journey.

A Message of Hope

The takeaway from this conversation is clear and powerful:

Even when first-line melanoma therapy fails, you are not out of options.

With continued research, expanding clinical trials, and the growing field of cell therapy, there are more opportunities than ever to find a treatment that fits your path forward.

Explore More Resources from AIM at Melanoma

You are not alone—AIM at Melanoma is here to help guide and support you every step of the way.