“It’s Like You Stuck a Pin in It:” African American/Black Patients Describe Cutaneous Toxicity From Epidermal Growth Factor Receptor Inhibitors

Abstract

Background:

Epidermal growth factor receptor (EGFR) inhibitors cause cutaneous toxicity in over 90% of patients. Conceivably, healthcare providers could overlook such toxicity in African American/Black patients because of a darker complexion. This qualitative study sought to learn about such cutaneous signs and symptoms and, if present, to report them in patients’ own words.

Methods:

Any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor was eligible. The current report focuses on patients’ responses to the following question, “What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?” All interview data were audio-recorded, transcribed, and then independently coded and analyzed by two investigators.

Results:

Fifteen patients are the focus of this report, and all described cutaneous toxicity. Patients appeared troubled by the cosmetic aspect of these drug-induced skin changes, including their acneiform appearance, describing “little pimples with little, little pus in it.” Notable were comments on hyperpigmentation, “I’m a black person but…. became darker.” Furthermore, patients experienced physical symptoms: “it itches;” “it’s like you stuck a pin in it;” “stinging;” and “burning;”.

Conclusion:

Although cutaneous toxicity from EGFR inhibitors might be more difficult to visualize among darkly complected patients, the graphic descriptions offered in this qualitative study underscore the need for clinicians to heighten their awareness of such toxicity in African American/Black patients.

Introduction

Epidermal growth factor receptor (EGFR) inhibitors are a class of antineoplastic agents that cause a rash in as many as 90% of patients.¹ This rash appears on the face, trunk, and proximal portions of all extremities.¹ Acneiform in appearance, this rash also burns and itches, generating both cosmetic as well as physical discomfort.

Relatively few studies have focused on this skin toxicity in African American/Black patients. A previous study from Phelps and others went so far as to try to explain seemingly reduced rates of adverse events in African American/Black patients who were prescribed these agents, suggesting that lower rates of adverse events from EGFR inhibitors might be attributable to CYP3A pharmacogenetic differences that lead to more rapid clearance of drug, less drug exposure, and therefore fewer drug-induced adverse events.² Of note, in the distant past, some investigators suggested that EGFR inhibitor-induced cutaneous signs and symptoms do not occur as frequently in African American/Black patients (link no longer active). More recently but importantly, a small number of case reports have focused on African American/Black patients with cutaneous adverse events, thus dispelling previous suggestions that these patients do not suffer from this drug-induced skin toxicity.³

Cutaneous drug toxicity is particularly problematic. Conceivably, healthcare providers could overlook a rash camouflaged by darker complexion. Yet, plausibly, this drug-induced cutaneous toxicity could perhaps cause a darkly complected patient substantial discomfort, as already observe in other groups of patients.⁴ Thus, this qualitative study was undertaken to address the fundamental question of whether African American/Black patients experience uncomfortable rash signs and symptoms, and, if so, to learn about such signs and symptoms in patients’ own words.

Methods

Overview.

The Mayo Clinic Institutional Review Board approved study #16–010618, which was undertaken to learn about EGFR inhibitor-induced cutaneous signs and symptoms in African American/Black patients in their own words. Although this study had integrated photo elicitation in its methodology, the current substudy focused specifically on whether cutaneous signs and symptoms were experienced and, if so, how patients characterized them.

Patient Recruitment.

The study protocol allowed for the recruitment of any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor. Because the rash might appear camouflaged, the presence of a rash itself was not included in the eligibility criteria. Mayo Clinic medical records were reviewed periodically for patients who met the inclusion criteria; the study team directly contacted these patients and asked them to enroll. Similarly, healthcare providers, including those external to Mayo Clinic, were asked to refer patients. All patients who completed verbal consent and signed a Health Insurance Portability and Accountability Act (HIPAA) form are included in this substudy.

Interview Methods.

Using an iterative process, the study team formulated a semistructured interview guide reflective of the goals of the study. The current report focused on only one of these questions, “What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?”

Three investigators conducted the interviews. None had worked with any of these patients in the past in either a research or clinical setting. All interviewers were women; two had a doctoral and one a bachelor’s degree. Each had undergone interview training.

Each interview was conducted by phone, audio recorded, and then transcribed with spot checks of transcripts for accuracy. Members of the study team reviewed interview transcripts in a real time manner, seeking evidence of saturation (no apparent new information), which would signal the conduct of no more interviews.

Data Analyses.

Two investigators then independently studied these transcripts, focusing specifically on patient-described cutaneous signs and symptoms and, if present, how patients characterized them. These two investigators met several times to discuss and organize the data, to draw conclusions, and to decide on direct patient quotations representative of study findings.

Results

Demographics and Related Data.

Fifteen patients are the focus of this report. Demographics appear in Table 1. The median time from rash development to the interview was 51 weeks (range: 1, 320 weeks); this information was unavailable in one patient. The median interview duration was 40 minutes (range: 9, 109 minutes).

Table 1.

Demographics (n = 15).

Characteristic	Number of patients (%)*
Median age, in years (range)	56 (35, 90)
Sex  Female	10 (67)
Male	5 (33)
Cancer  Colorectal	6 (40)
Lung	5 (33)
Breast	3 (20)
Head and neck	1 (7)
EGFR inhibitor**  panitumumab	6 (40)
erlotinib	2 (13)
afatinib	2 (13)
neratinib	1 (7)
osimertinib	1 (7)
lapatinib	1 (7)
cetuximab	1 (7)

^*Numbers represent percentages unless otherwise specified; percentages might not sum to 100% because of rounding.

^**Data missing for one patient. Although this patient was prescribed an EGFR inhibitor, it is unknown which one.

Two Themes: Cosmetic and Physical Discomfort.

The first theme focused on the cosmetic aspect of the rash, underscoring that the patients themselves visualized skin changes. These changes sometimes manifested as an acneiform rash. One patient described, “little pimples with little, little pus in it” (patient 1). Confirming the same, another stated, “Ah ha it’s like a white… thick ooze like, like oozing like a pimple” (patient 2). Another noted, “I see all those little bumps now” (patient 4). Confirming this finding, another noted, “So it would just show up like pimples” (patient 13). Another described, “Well, I noticed uh the first thing was that I got pimples on my nose” (patient 14). Yet another explained, “It was a little overwhelming because I was a kid that never had acne… and initially when I got one or two under my chin, you know, I wanted to - to- to bust them like they were a pimple” (patient 5). Another patient described these acneiform changes as follows, “On my face, it looked like, uh, it- it used to when you have, um, a blackhead, but it’s not blackhead. But when I squeeze it, it [becomes] a sore mixed with blood” (patient 8). Describing a similar characteristic of these skin changes, another patient noted, “The only stuff sometimes that concerns me may be the little black spots that develop after the bumps” (patient 10). Further elaborating on such bumps, a patient stated, “And…. I got bumps on the top of my head. But uh… um, they… they… I mean, I can still feel ‘em” (patient 11).

Not only did patients comment on the acneiform appearance of the rash, as described above, but a salient subtheme related to skin hyperpigmentation also emerged. One patient described, “But, I’m a black person but…. became darker” (patient 1). Another noted, “No, that’s since all the Tarceva, so you know maybe there was going to be a mole there anyway but… [it] became more pronounced” (patient 2). Attributing this hyperpigmentation to the EGFR inhibitor, another patient explained, “My feet and my hands are darker than the rest of my body” (patient 7). Alluding to this hyperpigmentation, another observed, “My face… is a little bit darker” (patient 10). Yet another patient explained, “But… because I mean I am black, but I’m like a fair, lighter skin black. So where the rashes were, it was extremely dark… in those areas” (patient 12). Another described, “I did notice dark rings” (patient 14). Referring to skin discoloration, another described, “It turns black” (patient 15). Providing insight into how troubling these skin changes were, one patient stated, “It was just ugly and it was uncomfortable in the sense of, you know, it’d gotten to the point where I didn’t wanna wear short-sleeved shirts cuz it started… then it started to spread as far as on my arms” (patient 12).

The second theme is the physical discomfort of this drug-induced skin toxicity. One patient noted, “Uh-huh, and then, and now it’s up in by my forehead ah it just it- it- it’s-…. Itch sometimes, you know” (patient 1). Explaining further, this patient noted, “And then it itches on my back and my neck and then one day I got lotion and I tried to reach it and I can’t reach it you know” (patient 1). Another simply described, “It itches” (patient 10). Notably, the degree of itching varied from patient to patient with one patient noting, “You can feel like an itch…. But it didn’t itch as much” (patient 6), and another noted, “The rashes weren’t really itchy” (patient 12).

In addition to itching, patients also described the physical discomfort of pain, “But the whole face gets like that and those white little bumps…. they ooze out um and they’re painful” (patient 2). This same patient described, “Because yeah and so if I press it with a Q-tip, the pain shoots it’s so deep, it’s like you stuck a pin in it” (patient 2). Another explained, “I had gotten actually like the blisters just- it was pretty bad I mean it was like… my face was in hot grease you know. And I had to take pain pills” (patient 3). This patient went on to elaborate, “But, when you’ve got big, bubbly monster blisters, that’s something damn painful” (patient 3). Another patient explained another component of this pain, “It can be pain… if you get… cracked feet. It can be painful painful….” (patient 9). Yet another described “it was in like a smart pain” (patient 13). This pain was sometimes characterized as “burning” (patient 3), “real… stinging” (patient 4), or even “itchy and burning” (patient 8).

Discussion

To our knowledge, this study is one of the few to focus on EGFR inhibitors prescribed to African American/Black patients and to allow these patients to describe the cutaneous toxicity from these agents in their own words. Of note, although patients’ healthcare providers did not have to discern a rash for patients to be eligible, it is perhaps inevitable that a study such as this one selected for patients with skin toxicity. Nonetheless, the current study is important because all fifteen of the patients interviewed experienced cosmetic discomfort, physical discomfort, or both from this class of agents, an observation that points to the importance of heightened awareness among clinicians. Indeed, the graphic nature of what these patients experienced underscores the need for healthcare providers to remain sensitive to such cutaneous toxicity and to provide patients with supportive care – such as topical moisturizers, pain medications, and EGFR inhibitor dose reductions – to help manage these signs and symptoms.¹

To date, the published literature has described how African American/Black patients have poorer cancer outcomes and even receive pain medications at a lower rate.^5,6 The current study is important because it underscores that African American/Black patients are truly suffering from cutaneous toxicity from EGFR inhibitors, underscoring a warning that this set of cutaneous symptomatology should not be overlooked or ignored. Importantly, it should be noted that many of the clinical trials with EGFR inhibitors did not specifically report the racial demographics of enrolled patients and generally did not comment on symptom severity based on any specific demographic. Thus, the results reported here – albeit within a small group of Black patients with cancer – give voice to these patients and provide important perspectives on the severity of their drug-induced signs and symptoms.

Finally, this study has limitations, the most notable of which is a lack of robust quantitative data. As a qualitative study, the current study does not provide data on how frequently African American/Black patients experience cutaneous signs and symptoms from EGFR inhibitors. Rather the purpose of this report was to seek evidence as to whether such toxicity occurs and, if so, to provide compelling data to convince clinicians to remain vigilant for such side effects. The direct patient quotations captured here provide such evidence and serve to compel clinicians to be more sensitive to the diverse manifestations of this drug-induced skin toxicity and to heighten their sensitivity for this cutaneous toxicity in African American/Black patients.