Do we need skin toxicity? Association of immune checkpoint inhibitor and tyrosine kinase inhibitor‐related cutaneous adverse events with outcomes in metastatic renal cell carcinoma

Abstract

Introduction Skin toxicity is a common, expected side effect of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) used for metastatic renal cell carcinoma (mRCC). We evaluated the association between skin toxicity and clinical efficacy outcomes of these agents in mRCC patients. Methods and Materials Data were obtained from patients with mRCC treated with TKIs and/or ICIs from 2016–2019 at a referral hospital in Mexico City. Clinical outcomes were compared among patients who developed treatment‐related cutaneous adverse events (AEs) and those without skin toxicity. Results Thirty‐five patients with mRCC were identified who were treated with sunitinib (51.4%), nivolumab plus cabozantinib (28.6%), nivolumab monotherapy (17.1%), or ipilimumab plus nivolumab plus cabozantinib (2.9%). Any grade skin toxicity was seen in 65.7% of patients. With a median follow‐up of 14 months, radiological responses were as follows: 48.6% stable disease, 25.7% partial response, and 2.8% complete response. Compared to subjects without skin toxicity, patients who developed cutaneous AEs had higher disease control rate 91.3% vs. 50.0% (P = 0.019) and superior 12‐month overall survival rate 91% vs. 67% (P = 0.01), respectively. There was a trend toward improved median progression‐free survival (16 months vs. 5 months, P = 0.13). Grade 1–2 cutaneous toxicity was found to be predictive for disease control, with HR 2.72 (95% CI 1.1–6.71, P = 0.030), and all grade cutaneous toxicity was prognostic of overall survival, with HR 0.18 (95% CI 0.04–0.91, P = 0.039). Conclusion Cutaneous AEs are associated with improved overall survival and response in patients with mRCC treated with immunotherapy and/or TKIs.

Skin manifestations associated with checkpoint inhibitors

“…30,66 Early studies seemed to support such notion in the context of ipilimumab, pembrolizumab, and nivolumab therapy for different cancers, among which the most frequently researched was metastatic melanoma. 46,[67][68][69][70][71][72] ICI-induced vitiligo-like depigmentation in patients treated for melanoma is associated with longer progression-free survival rates, overall survival rates and reduced risk of disease progression in comparison to patients who did not develop such irAE. 73 Skin depigmentation could therefore be considered an indicator of immunotherapy efficacy, as further endorsed by a single case report of a metastatic melanoma patient who presented repigmentation of vitiligo-like lesions after nivolumab discontinuation in concomitance with disease recurrence.…”

“…Although ICIs are a relatively new class of drugs, attempts at investigating the prognostic implications of cutaneous irAEs have been made in light of previous data confirming the association between skin toxicity from targeted therapy (e.g., with erlotinib, sunitinib, sorafenib) and treatment efficacy, response rates and overall survival rates 30,66 . Early studies seemed to support such notion in the context of ipilimumab, pembrolizumab, and nivolumab therapy for different cancers, among which the most frequently researched was metastatic melanoma 46,67–72 …”