Checkpoint inhibitor shows promise in advanced squamous-cell carcinoma

An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.

A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.

Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.

In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.

In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.

The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.

The treatment showed similar effects in patients with regional and distant metastatic disease.

Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

 

“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.

In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.

Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.

“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.

 

Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.

The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.

An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.

A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.

Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.

In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.

In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.

The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.

The treatment showed similar effects in patients with regional and distant metastatic disease.

Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

 

“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.

In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.

Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.

“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.

 

Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.

The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.

An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.

A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.

Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.

In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.

In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.

The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.

The treatment showed similar effects in patients with regional and distant metastatic disease.

Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

 

“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.

In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.

Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.

“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.

 

Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.

The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.