Patients with advanced NMSC show nuanced responses to immunotherapy

12 May 2021

Melbourne researchers have described a delayed response after confirmed progression (DR) in patients with cutaneous squamous cell carcinoma (cSCC) treated with immune checkpoint inhibitors (ICIs).

The researchers, from the Peter MacCallum Cancer Centre, reported three cases with unconfirmed disease progression after treatment of lesions with either cemiplimab or pembrolizumab.

Signs included increased size of lesion, new lesions, ulceration, coalescence of lesions, fungation and pain after the first two ICI treatments followed by clinical improvement around the time of the third treatment.

“These cases highlight the important consideration of the timing and method of disease response assessments and the limitations of most criteria to capture pseudoprogression/DR, response rates and best overall response (BOR) assessments as part of clinical trial reporting,” the researchers said.

The article, published in Frontiers in Oncology, also noted that other patients with cSCC or BCC have developed second primary tumours (SPT) while on immunotherapy.

“From a clinical management perspective, it is critical that SPT development is not mistaken as treatment failure given that these lesions can resolve with ongoing therapy or can be managed with local therapy,” they said.

“As a general principle, the SPT should be observed for a period whilst continuing immunotherapy and if regression or stability does not occur then local therapy can be pursued with a view of continuing systemic therapy for control of the other immunotherapy-responsive disease.”

They also presented a case which demonstrates the heterogeneity of response to immunotherapy within the same patient.

The patient had a locally recurrent lesion on his elbow which almost completely responded to cemiplimab by the third dose. Over the same period of time, a separate primary cSCC on his cheek continued to recur despite multiple excisions and re-excisions and later radiotherapy.

“Patient Four’s case demonstrates that discordant immunotherapy responses can be observed between lesions, where concurrent local therapy may be warranted in an attempt to secure control of immunotherapy-resistant lesions.”

The researchers, led by Dr Annette Lim, said their experience showed there were not many clinical situations in which disease was considered too advanced for immunotherapy.

“That is, the stage of disease, location of disease, and extent of disease does not militate against response to immunotherapy.”

They said ICIs were well tolerated even in patients with additional risks and comorbidities such as extreme age, dialysis, other synchronous malignancies or poor ECOG status.

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