Managing Expectations of Treatment for Infiltrative Basal Cell Carcinoma

Publication
Article
Peers & Perspectives in OncologyNovember I, 2023
Volume 1
Issue 8
Pages: 11

In an event comoderated by Michael K. Wong, MD, PhD, FRCPC, and Anokhi Jambusaria, MD, MSCE, the 2 key opinions leaders discussed the hypothetical patient case of an 88-year-old man with a nonhealing ulcer on the lateral aspect of his nose who received a diagnosis of infiltrative basal cell carcinoma.

Wong MK

Michael K. Wong, MD, PhD, FRCPC

Professor, Department of Melanoma Medical Oncology Division of Cancer Medicine

The University of Texas

MD Anderson Cancer Center

Houston, TX

Anokhi Jambusaria

Anokhi Jambusaria, MD, MSCE

Associate Professor, Department of Internal Medicine

Section Chief, General Dermatology, Department of Internal Medicine

The University of Texas at Austin Dell Medical School

Austin, TX

ADDRESSING SURGERY BEFORE ADMINISTERING THERAPY

WONG: For the medical oncologist, we'll see the patients [with] complex, high-risk [disease], and managing them means a multidisciplinary [approach]. I’m very lucky where I practice because our dermatology folks have a clinic next door to me, so I can always run down the hall and say, “I don’t know what this is, but could you come take a look at it?” Usually they’re smarter than I am, because from the doorway they’ll [already know what they’re looking at].

JAMBUSARIA: An important point to bring up here, especially for medical oncologists, [is that] if you ask any surgeon and show them a picture of this patient, I will argue that most surgeons would say, “Oh, we can easily cut this out.” I work very closely with some amazing surgeons, and my experience has been that they have told me that basically anything is operable. You could, in theory, cut out anything.

There’s some shared decision-making involved with the multidisciplinary team and the patient, [and they all need to ask], “What does that surgery involve? What is the morbidity and mortality of the surgery? What are the functional issues at play?”

If you’re going to [perform surgery on] someone’s ear, for example, because the cancer is eating into their ear, that might not be ideal for certain patients. I can only speak from the dermatologist standpoint, [because] a lot of my colleagues out in practice don’t have as much experience with some of these [newer] immunotherapy medications. They don’t know what’s involved in terms of infusions and toxicity risks, and if you have a good relationship with some of your referring dermatologists, I will encourage [the medical oncologist to] bring this up with them. Because if the surgery planned would be very invasive, [then giving therapy first] might be the right option for that kind of patient to consider.

WONG: Well, immunotherapy has only been around for about 11 years.... The use of anti–PD-1 therapies in skin cancer, especially [for patients with] basal cell carcinoma, is measured in a couple of years and in squamous cell [management] maybe 3 years. So this is all brand-new stuff, and The University of Texas MD Anderson Cancer Center is my fourth NCI [National Cancer Institute] cancer center. And [at] the other ones I’ve worked at, which are much smaller, what happens is you develop a team approach, have a referral base, and you begin to develop a workflow around sequencing [these treatment options], and that’s important. I’ve sat on several National Comprehensive Cancer Network [NCCN] guideline committees, and the NCCN guidelines tell you what you can do, but they never tell you what you should do.

[In the NCCN guidelines], it starts with multidisciplinary consultation, because [in some scenarios] you can get disease reduction with some of the drugs that we have, which will make it possibly easier for the surgeon to operate.1 We had a case of someone who had...a 10 × 14-cm basal cell tumor on his back, and you could almost see the spinal processes in a muscle. He went on 8 months of a hedgehog inhibitor, [had resection performed] and was tumor free, and then got more hedgehog inhibitor [therapy].

WHEN TO IMAGE AND TEST THESE PATIENTS

WONG: I bring the surgical folks into the process, so [we need a] very good physical examination, which can help you, but I have a low threshold for imaging because many of the patients I see have had these situations fester for quite a while. It’s not unusual for me to have someone come in with basal cell [carcinoma] that’s been active for years. So that’s my practice, and I have a low threshold for imaging where, usually, I would image a nodal basin. In some of these situations, surgeons may have already done an MRI of the face to assess resectability and association with underlying structures and plan out an operative approach.

[In that way], my practice is a little different, because [patients who] come to us have much more advanced disease. The [situation with the patient who had a] 10 × 14-cm lesion in their back had CT imaging for nodal spread; a CT body scan because of the size and length of time it was on the back. [The patient also had] MRI of the spine to look at the bone structure and MRI of the soft tissue to see an association of the vascular nerve. So that’s one end of the spectrum, but once you are in a situation where you’re contemplating systemic therapy in a bulky lesion, that’s the trigger point. Bulky for me is that 2-cm threshold. That plus long residency time triggers me to do that [imaging for the patient].

JAMBUSARIA: [For those] patients who have had tumors for a long time, when you see that infiltrative histology, the other high-risk subtype [to look for] is micronodular. If you see that on a pathology report, especially in larger tumors, these would be reasons I would recommend imaging to see whether it had spread. Based on physical exam, if they’re having…symptoms where there might be some perineural invasion, that would prompt me to do MRI as well.

CONSIDERING CEMIPLIMAB’S STABILITY AND TOXICITIES

WONG: [In the phase 2 clinical trial (NCT03132636) results], the complete response [CR] rate with [cemiplimab (Libtayo)] was 6% but the objective response rate was 31%.2 So a small proportion of patients have CRs, which is amazing in a refractory population. However, you have to set your expectations correctly [because] half of patients had stable disease, and that’s why, when you are looking at a selection of drugs, I always say that it’s better to chain together 2 medicines, one after the other, that can give you a long-term response. We’re not curing most patients here, so [a long-term response is] important. Nevertheless, [patients] who were continuing the study, and most patients are, show there is a longevity to the duration of response [DOR].

A DOR greater than 12 months was seen in 46% of patients, so almost half [of] patients had at least 12 months, if not more, of response [to the therapy].2 So it’s a drug that can provide long-term control. Again, setting expectations appropriately...you’re not going to cure most patients here. Some of the responses can occur late. So the other thing here is you don’t want to bail out too quickly and say, “Well, it’s not working.” What you typically see in these long-term responders is some stability of disease and then the response [to treatment].

A median overall survival [OS] was not reached, but the 2-year OS rate was 80%.2 One of the things that I look for as I go to ASCO [the American Society of Clinical Oncology Annual Meeting] [or other oncology meetings] every year is the updates to their progression-free survival [PFS]. Is there going to be a plateau here [in the future]? I expect so, because 57% of patients had at least 12 months PFS, but as the data mature, they might show a plateau, which shows a stability response.

[However], the flip side of efficacy is always toxicity, and I would say that cemiplimab is in line [with toxicities seen] in the anti–PD-1 class of drugs [Table2]. You don’t have a lot of high-grade toxicity, but fatigue is a dominant issue. Still, the conclusion from the study authors was that there are no new safety signals from this study. So you can feel confident that your expertise and fluency with other PD-1 inhibitors’ toxicities translates to [cemiplimab].

table: cemiplimab trial

JAMBUSARIA: [When it comes to older patients with worse functional status on this treatment], it’s tough, because they may not tolerate treatment or respond to treatment the way somebody 30 years younger than them would. It’s not just [about whether] they tolerate the treatment, whether it’s surgery, radiation, or immunotherapy, but what are some of their social factors? For example, are they able to take care of themselves? Are they able to drive and make it to the doctor’s appointments, infusions, or radiation appointments? So there are some social issues at play when making some of these decisions for patients. There are also thoughts about [the patients’] functional goals with where the tumor is and maybe some important structures that it might be nearby.

With most of these tumors that are on the head and neck, there are some important structures even aside from a cosmetic perspective, from a functional perspective, [that] are very important and [even more] important as you get older. For example, tumors around the eye [where] you can’t see and your quality of life is very poor. Or big cancers around the ears, because they take out your ears. Your hearing is already bad, [but] now your hearing is even worse. So those can be huge quality-of-life issues. These are functional considerations to be made when you’re thinking about some of these treatments.

REFERENCES

1. NCCN. Clinical Practice Guidelines in Oncology. Basal cell carcinoma, version 1.2023. Accessed October 11, 2023. https://tinyurl.com/5dp97yys

2. Stratigos AJ, Sekulic A, Peris K, et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):848-857. doi:10.1016/ S1470-2045(21)00126-1

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