Cancer Topics - Contrasting Cases: Long-Term Outcomes and Responses to Retreatment in Patients With Melanoma Treated With PD-1 Blockade

Dr. Doug Johnson is an Associate Professor of Medicine and Leader of Melanoma Program at the VanDr. Doug Johnson is an Associate Professor of Medicine and Leader of Melanoma Program at the Vanderbilt Ingraham Cancer Center in Nasheville, TN. In today’s ASCO eLearning Podcast, Dr. Johnson discusses two patient cases related to stopping of anti-PD-1 and consideration of retreatment for metastatic melanoma. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/].

 

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Hello, my name is Doug Johnson. I'm an associate professor of medicine and leader of the Melanoma Program at Vanderbilt-Ingram Cancer Center. Today we compare two patient cases that relate to stopping of Anti PD-1 therapy in consideration of whether to re-treat patients that have metastatic melanoma. These two cases have similarities, yet the recommended treatments may be different.

 

Let's look at the cases. Patient case one. Our first patient case is Dave. Dave is a 62-year-old man with metastatic melanoma involving the lungs and liver. He was treated with single agent nivolumab and he had decreasing size of one of his lung metastases but had increasing liver metastases when his first CT scan was performed.

 

Since his melanoma has a BRAF V600e mutation, he was switched to BRAF and MEK inhibitors, which were later followed by progression and 12 months on therapy.

 

Patient case two. Our second patient case is Rachel. Rachel's a 55-year-old woman with metastatic BRAF wild type melanoma involving the lungs and liver as well. She receives pembrolizumab with a complete response and therapy is stopped after 15 months of treatment.

 

Two years later, she has growth of two of her lung lesions and a biopsy confirms that this is melanoma.

 

So questions for consideration. As you can see, both cases involve progression of anti PD-1 therapy, but there are some differences. Do the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? In particular, would you consider anti PD-1 re-treatment for either or both of these patients?

 

Some background. The standard treatment for metastatic melanoma, regardless of BRAF mutation status, is Anti PD-1 monotherapy, either with nivolumab or pembrolizumab. Approximately 44% of patients experience complete responses to treatment, many of which are durable. Many patients with complete or near complete responses have a discussion with their oncologist and elect to stop treatment after one to two years on therapy. However, about one third of patients who have a response ultimately experience disease progression.

 

The treatments who either respond to Anti PD-1 and then later progress or patients who never respond at all is an important issue to consider. Options for these patients include ipilimumab monotherapy, ipilimumab in combination with nivolumab, or if BRAF mutated, BRAF and MEK inhibitor therapy. Re-treatment with Anti PD-1 may be an option as well.

 

Other melanoma therapies have shown benefit with re-treatment with this type of strategy. For example, patients re-treated with BRAF and MEK inhibitors, provided they took at least a six week break off therapy, have nearly a 50% response rate to re-treatment. In addition, patients who benefited from ipilimumab then later progressed had at least a 20% response rate to re-treatment.

 

So how are these cases related? Both patients experienced progression either on or following Anti PD-1 treatment. However, there are some key differences as well. Patient one progressed while still receiving treatment, and at least his liver lesions never responded to therapy at all.

 

On the other hand, patient two experienced progression a long interval after completing treatment. She also had an objective response, in fact, a complete response to her initial course of therapy.

 

So what should we do with these patients? Well, the answer, from my perspective, is patient one should not receive re-treatment with Anti PD-1 therapy. A recent publication by Dr. [? Betof ?] and colleagues in JCO studied 396 patients with long-term follow-up following Anti PD-1 treatment. This included 34 patients who were re-treated. None of the patients who initially progressed on therapy, so those who didn't have a complete response, were prolonged stable disease. None of those patients experienced long-term benefit with re-treatment.

 

On the other hand, these patients did benefit from ipilimumab and nivolumab 25% of the time, with a 25% response rate. Additional patients also experienced stable disease in this group. Thus, either ipilimumab and nivolumab or [INAUDIBLE] monotherapy should be considered for patient one.

 

Patient two, by contrast, had a durable complete response to therapy and progressed after completion of treatment. This patient could consider re-treatment with Anti PD-1. A study by Dr. Warner suggested that of patients in this position, those who had an initial objective response to treatment, only 15% of patients had objective responses. However, durable benefit was more frequently seen in patients who had complete or partial response to their initial course. Many patients had prolonged stable disease with re-treatment.

 

Thus, re-treatment could be considered in this patient. Or we would also be reasonable to think about ipilimumab and nivolumab combination or ipilimumab alone. That would also be appropriate for this patient.

 

In closing, thank you for listening to this week's episode of ASCO e-learning weekly podcast. For more information on treatment for metastatic melanoma, including additional patient cases and opportunities for self-evaluation, visit the comprehensive e-learning center at e-learning.asco.org. Thank you.

 

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