Multidisciplinary Discussions Shape Systemic and Surgical Skin Cancer Treatment

Future advances in melanoma and other skin cancers should focus on team-oriented care and increasingly informed treatment sequencing regarding the roles of immunotherapy, targeted therapy, and surgery, according to Carlo Contreras, MD, who emphasized that although unmet needs still exist in many areas, the armamentarium is becoming better defined.

“All this information is exciting to be able to offer to patients, and it also brings new challenges when finding the best ways to implement [these therapies] in our multidisciplinary clinics,” Contreras said in an interview with OncLive^® following an Institutional Perspectives in Cancer webinar on melanoma, which he chaired.

In the interview, Contreras shared key insights from the meeting, including the treatment horizons in cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC), the implications of the phase 3 DREAMseq (NCT02224781) trial in BRAF V600E–mutant melanoma, and the potential for personalized therapeutic and surgical care in desmoplastic melanoma.

Contreras is a surgical oncologist at The Ohio State University Comprehensive Cancer Center (OSUCCC)–James in Columbus.

OncLive^®: What did you highlight in your presentation on CSCC and BCC treatment updates?

Contreras: We took a look at 2 of the main types of medication pathways that are used for patients with locally advanced or metastatic disease. We talked about how different strategies have evolved with respect to picking specific agents, especially hedgehog inhibitors. We also evaluated the role of immunotherapy for both CSCC and BCC, which have typically been more prominently used for melanoma, rather than non-melanoma skin cancers.

How have both these treatment landscapes evolved over time?

Going back 15 years or so, neither of these paradigms existed. Now they’re available, and we have multiple choices in each of these pathways to exploit in our patients with locally advanced or metastatic tumors.

Since we have options, we have robust discussions about which options are better individual choices for patients based on a variety of tumor-related characteristics, as well as a number of patient-related characteristics. Additionally, we now have a new set of data about neoadjuvant therapy with immune checkpoint inhibitors.

What unmet needs remain in CSCC and BCC, and how might they be addressed going forward?

The unmet needs with BCC and squamous cell carcinoma are head-to-head, randomized clinical trials with hedgehog inhibitors. For a variety of reasons, it’s unlikely that we’ll ever see those trials conducted. But in CSCC and BCC, we look to see larger trials to replicate the promising results we’ve seen in the early trials, especially with neoadjuvant therapy.

We’re also interested in looking at the longer-term data, especially for the neoadjuvant trials, to understand whether these are durable responses to therapy, or whether these patients are at risk for relatively short-term recurrence. Some of the melanoma literature [shows that], especially with neoadjuvant BRAF-directed therapy, while patients have an impressive pathologic complete response [pCR], they are at risk for relatively short-term recurrence within the first 2 years after resection. The degree of pathologic response that we’re seeing [with other diseases], especially in CSCC, are on par with what we saw in melanoma. Hopefully, these will be more durable responses than what we saw in the melanoma literature, [although that remains to be seen].

Regarding the presentation Claire Verschraegen, MD, MS, FACP, of OSUCCC–James, gave, what is important to know about treatment sequencing in melanoma?

It’s a wonderful and exciting time to be practicing [in melanoma] because we have options. [However,] we don’t have clear answers about the sequence of therapy, when to begin therapy, which type of therapy to begin with, when to integrate surgical resection into patients’ care, and how to tailor the therapy, [if administered,] in the post-operative setting. Here again, we don’t have head-to-head comparisons of all these different treatment approaches, but further study will help clarify some of these questions.

It’s important to know that we have options. This underscores the importance of a true multidisciplinary care model where we can discuss these individual patient cases with the shared expertise of all the different disciplines that come to sit at the table and participate in the care of each patient.

Richard Wu, MD, PhD, of OSUCCC–James, spoke about the importance of BRAF V600E. How do the results from the DREAMseq trial clarify treatment sequencing with immunotherapy and targeted therapy in patients with this mutation?

[From this trial,] we do have high-level data with good follow-up showing that immunotherapy followed by BRAF-directed therapy is the ideal sequence for patients with advanced melanoma who need multi-modality care with different drug mechanisms. This was a pivotal trial. We’ve already seen how it has affected our daily clinical care decisions.

Kari Kendra, MD, PhD, of OSUCCC–James, presented on the phase 2 SWOG 1512 trial (NCT02775851)and neoadjuvant immunotherapy for desmoplastic melanoma. What does this trial indicate about the role of neoadjuvant pembrolizumab (Keytruda) in this disease subset?

This was another example of a pivotal trial that we [also need to consider] in the context of the [phase 2] SWOG 1801 trial [NCT03698019]. Both had relatively similar trial designs [that included] patients with resectable stage III or IV melanoma [or resectable or unresectable desmoplastic melanoma. In SWOG 1801, patients] were randomized to receive [adjuvant or perioperative immunotherapy] in [the form of] single-agent immune checkpoint inhibition, [and in SWOG 1512, patients received] neoadjuvant immunotherapy [or immunotherapy alone]. In each situation, both all comers with cutaneous melanoma and the desmoplastic melanoma population had excellent response rates with preoperative immunotherapy.

It’s entirely possible that we may be able to individualize the extent of the operation after neoadjuvant therapy based on the response that we see. Especially for desmoplastic melanoma, future studies may be important for understanding what we need to resect and identifying a subset of patients that may not need surgical resection after successful completion of neoadjuvant therapy.

Our unmet needs are a bit different [in this population than in other melanoma subsets]. The challenge is that while patients may have what appears to be a complete clinical response, we can’t prove that that always correlates with a pCR. The [SWOG 1512] data are certainly promising, but some patients can still have recurrence if they don’t have the completed resection.

[These data] also allow us the opportunity to escalate therapy for patients who receive those first few doses of neoadjuvant therapy but don’t have the anticipated clinical response [because] the tumor continues to grow or progress. That is a particularly high-risk set of patients that would generally benefit from a more aggressive systemic regimen, or, if the tumors are encroaching upon critical structures, would benefit from earlier, more aggressive surgical resection to avoid the compromise of essential anatomic structures.

What ongoing melanoma research at Ohio State are you involved in?

I am the principal investigator on a trial that is evaluating the role of an intralesional influenza vaccine in patients with early-stage melanoma and later-stage melanoma. Promising data suggest that intralesional influenza may stimulate an immune response within the tumor that could affect tumor regression before we operate or may augment the efficacy of immunotherapy when given concurrently.

This is an investigator-initiated trial [running] exclusively here at The Ohio State University that’s currently enrolling patients. Our goal is to enroll patients in 2 cohorts. One [cohort will be patients] with early-stage disease who we will take to the operating room for a standard-of-care [SOC] melanoma resection with sentinel lymph node biopsy. Our second cohort [will be] patients who have been diagnosed with metastatic melanoma with at least 1 injectable tumor site who will receive SOC immunotherapy. We will inject [the patients in cohort 2 with] the intralesional influenza vaccine with concurrent immunotherapy to understand how the tumor responds at the injected site as well as at the non-injected sites.

The influenza vaccine we’re using in this clinical trial is an off-the-shelf, FDA-approved, unadjuvanted influenza vaccine. To this point, it has been well tolerated, and we are looking to continue to screen and enroll patients who meet our eligibility criteria.