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The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in melanoma and health equity.

First, Dr. Katy Tsai discusses new research in melanoma.

Dr. Tsai is a medical oncologist and Assistant Professor of Medicine in the Division of Hematology and Oncology at the University of California, San Francisco. She is also the 2023 Cancer.Net Associate Editor for Melanoma & Skin Cancer.

You can view Dr. Tsai’s disclosures at Cancer.Net.

Dr. Tsai: Hello. Welcome to the ASCO Cancer.Net Research Round Up. I'm Katy Tsai, an associate professor of medicine and the clinical medical director of the Melanoma and Skin Cancer Program at the University of California, San Francisco. I'm happy to be here today to discuss research on melanoma and skin cancers presented at the 2023 ASCO Annual Meeting. I do not have any disclosures relevant to the studies to be discussed.

So, it's always exciting to see the latest research presented at ASCO. One theme in particular that I'd like to highlight in this podcast is recent advances in the field of adjuvant therapy. For the listeners who may not be familiar with this terminology, adjuvant therapy refers to drugs given after surgery to try to decrease the risk of cancer recurrence. Specifically, late-breaking abstract 9505 presented updates from KEYNOTE-716, an adjuvant study of pembrolizumab, or pembro, in patients with resected high-risk stage II melanoma. Late-breaking abstract 9503, which I'll also discuss, presented data from KEYNOTE-942, a pivotal study of a personalized cancer vaccine plus pembrolizumab in patients with resected high-risk stage III and stage IV melanoma.

So, let's start with KEYNOTE-716. We've known for some time in our field now that adjuvant pembrolizumab or nivolumab can help decrease the risk of recurrence for patients with resected stage III or IV melanoma. What may not be as well-known, however, is that patients with stage IIB or IIC melanomas, in other words, thicker, ulcerated primary melanomas, even without lymph node spread, actually have a comparable risk of melanoma recurrence compared to patients with early stage III melanomas. KEYNOTE-716 was a large, international phase 3 study that randomized patients with stages IIB and C melanoma to receive either pembro or placebo. The positive results showing improvement in relapse-free survival led to approval of adjuvant pembro in December 2021, but what was presented at ASCO was an update on distant metastasis-free survival. This is obviously an important endpoint for us because ultimately, if someone is going to develop widely metastatic disease, unfortunately, it is a development of these distant metastases that we are concerned about. So what we saw here is that with landmark 36-month follow-up, there was a 41% reduction in the risk of developing distant metastasis in patients who were treated with pembro compared to those who received the placebo. In addition, there was a consistent maintained benefit in relapse-free survival, and importantly, no changes in the side effect profile. These are important data because I believe it is practice-changing in the sense that this is a population of patients who historically might not ever have been referred to medical oncology, maybe just monitored serially with their dermatologists. And this is an option that should be discussed.

Ultimately, the risk versus benefit about whether to pursue a year of therapy versus maybe consider treatment only at the time of recurrence is a very personalized discussion between a patient and their treating oncologist, but it is an option that should definitely be offered. So let's move on to KEYNOTE-942. The novel drug being tested in this trial is very exciting. We're calling it “individualized neoantigen therapy.” So this is basically a platform that allows us to develop individualized treatment for someone based on characteristics of their own cancer. This involves taking the actual tumor specimen, genomic sequencing, specifically whole-exome sequencing is performed to try to identify any changes in the DNA. And then through a bioinformatic pipeline, the mutations in the DNA that are thought to be most likely to generate proteins that can be bound within presenting molecules are then identified in the computer program, then synthesized within mRNA. So very similar to the way that COVID vaccines have been made. So this actually becomes the actual drug product. So in this study, patients were randomized to receive either pembrolizumab by itself for a year, which is, as we alluded to earlier, standard adjuvant therapy, but then with the addition of this individualized neoantigen therapy starting with dose 3 and then throughout the rest of the year.

So the recurrence-free survival data were actually presented earlier this year at another major conference, AACR [American Association for Cancer Research], and were highly positive. At ASCO 2023, I think what was most impressive about the presented data is that distant metastasis-free survival, so again, a similar important endpoint that we discussed with the other trial, is that the distant metastasis-free survival here was quite impressively maintained. There was a hazard ratio of .35, meaning really a 65% reduction in the risk of recurrence for patients who received the personalized neoantigen therapy plus pembrolizumab. So this is a huge advantage for distant metastasis-free survival in this particular population of patients. What was even more intriguing is that usually when we combine therapies, we tend to see additive toxicity, more side effects. And what was really exciting about this particular trial is that the additive toxicity really wasn't as much as you would expect for giving 2 immunotherapies at the same time. I'll also highlight that even though these results are really exciting within melanoma, that part of the reason this data is so exciting is that it represents a really promising platform for therapeutic development and application in other tumors besides melanoma.

So this is definitely super exciting. While perhaps not practice-changing in this moment, it’s potentially practice-changing. And I look forward to seeing additional data coming in from planned trials using this particular combination in the metastatic setting in addition to the adjuvant setting.

So on the whole, I do think that updates in adjuvant therapy for melanoma were super exciting to see at ASCO 2023. As I mentioned earlier, it's a very large conference. A lot of exciting data being presented. So I do think that other themes to pay attention to as we continue to sort through existing data and look forward to incoming data from forthcoming trials is looking at neoadjuvant therapy. For example, drug given before surgery to try to improve long-term outcomes. For example, at ASCO this year, there was interesting neoadjuvant immunotherapy data presented not for melanoma, but for a different type of skin cancer called squamous cell carcinoma. So that would definitely be another theme to pay attention to in the coming months and years.

Thinking about novel combinations, for example, what's new in immune checkpoint inhibitors, we've been used to for a long time referring only to anti-PD1 antibodies, anti-CTLA4 antibodies. What was interesting to see this year were updates in novel combinations, for example, PD1 antibodies combined with LAG3 antibodies. Antibodies against TIGIT. So I think this will be another exciting space to pay attention to both in the metastatic skin cancer setting and in the adjuvant and neoadjuvant settings.

Thank you for your time and attention. That concludes my research roundup for melanoma and skin cancers. Thank you.

ASCO: Thank you, Dr. Tsai.

Next, Dr. Manali Patel discusses new research in health equity. Dr. Patel is a medical oncologist and Assistant Professor of Medicine at Stanford University. She is also the 2023 Cancer.Net Associate Editor for Health Equity.

You can view Dr. Patel’s disclosures at Cancer.Net.

Dr. Patel: Hi, my name is Manali Patel. I'm the Associate Editor for Health Eq