Real-world Data Demonstrate Strength, Durability of Checkpoint Inhibitor Use in cSCC

Response, progression-free survival, overall survival, time-to-next-treatment, and toxicity outcomes were evaluated among patients with advanced cutaneous squamous cell carcinoma (cSCC) who received first-line treatment with immune checkpoint inhibitors.

Patients who have advanced cutaneous squamous cell carcinoma (cSCC) continue to benefit from treatment with checkpoint inhibitors, especially in the first-line setting, with new data demonstrating the strength and durability of their responses. Study findings appeared recently in Cancers, and they encompass data on real-world cohorts and patients not eligible for clinical trials—data the study authors say are lacking in the skin cancer setting.

“cSCC is one of the most common malignancies of the skin with poor survival outcomes in advanced stages of the disease,” they wrote. “Recent clinical trials demonstrated the efficacy of checkpoint inhibitor therapy for advanced stage disease, but there is a lack of data from real-world cohorts and trial-ineligible patients.”

Thirty-nine patients made up the cohort in their retrospective, real-world study, and they received care at 8 German cancer centers registered within the multicenter registry ADOReg. Their response, progression-free survival (PFS), overall survival (OS), time-to-next-treatment (TTNT), and toxicity outcomes were evaluated, and they were stratified by immune status. They were included in this analysis because they had locally advanced, regionally or distant metastatic, or inoperable cSCC and a history of at least 1 dose of a checkpoint inhibitor in the first-line setting between February 2018 and June 2022. The primary end point was OS, and PFS, real-world tumor response, and severe treatment-related adverse events were secondary end points.

Twenty percent of patients overall experienced durable remissions, with checkpoint inhibitor treatment also having a positive impact against tumors in patients who have autoimmune conditions and lymphoproliferative disorders—although to a lesser extent and ultimately resulting in shortened OS.

The overall tumor response rate was 48.6%, and the median PFS was 29 months; median OS was not reached. Nine of the 39 patients demonstrated impaired immunity, which was attributed to immunosuppressive medication for an autoimmune disease (Crohn disease, autoimmune hepatitis, Lichen planus) or hematological diseases (chronic lymphocytic leukemia, polycythemia vera). When considering response among only these study participants, their tumor response rate (50.0%) following checkpoint inhibitor therapy was comparable to the overall rate, but the following outcomes were significantly shorter:

  • PFS: 11 vs 40 months (P = .059)
  • TTNT: 12 months vs not reached (P = .016)
  • OS: 29 months vs not reached (P < .001)

At baseline, 60.7% of all patients (84.6% were male patients) had an ECOG performance status of 1 or below (P = .062) and had stage III or IV disease (51.3%). Head and neck were the most common locations of the patients’ cSCC (64.1%), followed by limb (20.5%), trunk (10.3%), and genitoanal area (5.1%); the most common high-risk feature was poorly differentiated histology (30.8%); lymphatic tissue was the most common site of metastasis (59.0%); and surgery plus radiotherapy was the most common initial treatment regimen (51.3%).

The investigators’ analysis also found the following:

  • Univariate Cox regression analysis found associations between longer treatment duration, response to treatment, and good performance status with longer PFS.
  • Response to first-line treatment and lack of immunosuppression positively correlated with OS.
  • Multivariable Cox regression analysis found that OS was associated with presence of immunosuppression and best response to inhibitor therapy.

Just 15.4% of patients overall stopped treatment due to toxicity—grade 2 pneumonitis, grade 3 hepatitis, fatigue—after a median 9 months, and only 3 of these patients relapsed. For the 10 patients who experienced disease progression after initial checkpoint inhibitor treatment, 7 received another course of checkpoint inhibitor treatment and 1 each received taxol-based chemotherapy, cetuximab, and cemplimab plus cetuximab.

The most common checkpoint inhibitor administered was cemiplimab in 48.7%, and the median treatment duration was 5 months. Ten patients achieved a complete response, and 7 patients showed a partial response.

“Our data confirmed efficacy results for first-line [checkpoint inhibitor] therapy from previous clinical trials, transferring them into real-world cases. Further, we observed that checkpoint inhibitor treatment evoked durable responses, particularly among immunocompetent patients that showed at least a partial response,” the authors wrote when discussing the clinical implications of their findings. “Most importantly, our real-world data allowed us to better define the efficacy and safety of this therapy in a subgroup of immunocompromised patients.


Haist M, Stege H, Lang BM, et al. Response to first-line treatment with immune-checkpoint inhibitors in patients with advanced cutaneous squamous cell carcinoma: a multicenter, retrospective analysis from the German ADOReg Registry. Cancers (Basel). Published online November 11, 2022. doi:10.3390/cancers14225543

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