In the Journals

Pembrolizumab prolongs survival as first-line treatment for advanced Merkel cell carcinoma

Adam Riker, MD, FACS
Adam Riker

Patients with advanced Merkel cell carcinoma who received pembrolizumab as a first-line therapy demonstrated durable tumor control, manageable toxicity and longer OS compared with historical data from patients treated with first-line chemotherapy, according to results of a multicenter, phase 2 nonrandomized study.

“The results of this trial show how effective such a form of immunotherapy can be for Merkel cell carcinoma. Our published manuscript in Journal of Clinical Oncology shows that pembrolizumab [Keytruda, Merck] demonstrates durable tumor control, a manageable safety profile, and favorable overall survival when compared to patients who were treated with chemotherapy,” Adam Riker, MD, FACS, professor at Louisiana State University and chief of surgical oncology at Stanley S. Scott Cancer Center, told HemOnc Today. “This study also shows the longest follow-up to date of any study for patients with advanced Merkel cell carcinoma treated with a first-line anti-PD1 therapy. As of today, an anti-PD1 therapy, whether with pembrolizumab or another anti-PD1 antibody, should be considered for first-line therapy for patients with advanced and metastatic Merkel cell carcinoma.”

Merkel cell carcinoma remains rare, although annual incidence of the aggressive skin cancer increased by 95% in the United States between 2000 and 2013, fueled by growth of the population older than 60 years.

Five-year OS rates range from 14% to 27% among patients with advanced or unresectable disease.

The phase 2 trial represented the longest observation to date of patients with advanced Merkel cell carcinoma treated with any anti-PD-1 therapy in the first-line setting, according to researchers.

None of the 50 participants (median age, 70.5 years, range, 46-91; 68% men) in the study had prior systemic therapy for advanced Merkel cell carcinoma, although three received adjuvant chemotherapy for more than 6 months before starting the trial. Most (86%) had stage IV disease and 64% had Merkel cell polyomavirus-positive tumors.

All participants received 2 mg/kg pembrolizumab, an anti-PD-1 monoclonal antibody, every 3 weeks for up to 2 years.

Objective response rate, measured by RECIST version 1.1 criteria, served as the primary endpoint. Secondary endpoints included duration of response, PFS and OS.

Median follow-up was 14.9 months (range, 0.4-36.4+).

Results showed an ORR of 56% (95% CI, 41.3-70) to pembrolizumab, including 12 complete responses and 16 partial responses. Researchers observed ORRs of 59% in virus-positive tumors and 53% in virus-negative tumors.

Among the 28 responders, median duration of response was not reached (range, 5.9-34.5+ months).

The 24-month PFS rate was 48.3%, median PFS was 16.8 months (95% CI, 4.6-not estimable) and the 24-month OS rate was 68.7%. Median OS was not reached.

Investigators noted a trend toward improved PFS and OS among patients with PD-L1-positive tumors.

The overall results compared favorably with historical data of patients who received first-line chemotherapy for advanced Merkel cell carcinoma in two studies. Those data showed only 6% of patients with persistent responses at 18 to 24 months, median PFS of 3.1 months and 4.6 months, and median OS of 9.5 months and 10.2 months.

In the pembrolizumab study, Grade 3 or greater treatment-related adverse events occurred in 14 patients, with seven discontinuing treatment due to these events. Researchers reported one treatment-related death.

The results of the study supported the FDA accelerated approval of pembrolizumab as first-line treatment for adults and children with recurrent or locally advanced or metastatic Merkel cell carcinoma.

“Merkel cell carcinoma is indeed an immunogenic cancer, very similar to that found in other types of skin cancer, especially the most lethal form of skin cancer, melanoma,” Riker said. “Pembrolizumab has not been extensively examined for the more common, and less lethal forms of skin cancer, such as basal cell and squamous cell carcinoma.”– by John DeRosier

For more information:

Adam Riker, MD, FACS, can be reached at Louisiana State University School of Medicine, 7th floor, 1542 Tulane Ave., New Orleans, LA 70112; email: ariker@lsuhsc.edu

Disclosures: Riker reports a consultant or advisory role with Novartis and honoraria and speakers’ bureau fees from Castle Biosciences and Genomic Health. Please see the study for all other authors’ relevant financial disclosures.

 

Adam Riker, MD, FACS
Adam Riker

Patients with advanced Merkel cell carcinoma who received pembrolizumab as a first-line therapy demonstrated durable tumor control, manageable toxicity and longer OS compared with historical data from patients treated with first-line chemotherapy, according to results of a multicenter, phase 2 nonrandomized study.

“The results of this trial show how effective such a form of immunotherapy can be for Merkel cell carcinoma. Our published manuscript in Journal of Clinical Oncology shows that pembrolizumab [Keytruda, Merck] demonstrates durable tumor control, a manageable safety profile, and favorable overall survival when compared to patients who were treated with chemotherapy,” Adam Riker, MD, FACS, professor at Louisiana State University and chief of surgical oncology at Stanley S. Scott Cancer Center, told HemOnc Today. “This study also shows the longest follow-up to date of any study for patients with advanced Merkel cell carcinoma treated with a first-line anti-PD1 therapy. As of today, an anti-PD1 therapy, whether with pembrolizumab or another anti-PD1 antibody, should be considered for first-line therapy for patients with advanced and metastatic Merkel cell carcinoma.”

Merkel cell carcinoma remains rare, although annual incidence of the aggressive skin cancer increased by 95% in the United States between 2000 and 2013, fueled by growth of the population older than 60 years.

Five-year OS rates range from 14% to 27% among patients with advanced or unresectable disease.

The phase 2 trial represented the longest observation to date of patients with advanced Merkel cell carcinoma treated with any anti-PD-1 therapy in the first-line setting, according to researchers.

None of the 50 participants (median age, 70.5 years, range, 46-91; 68% men) in the study had prior systemic therapy for advanced Merkel cell carcinoma, although three received adjuvant chemotherapy for more than 6 months before starting the trial. Most (86%) had stage IV disease and 64% had Merkel cell polyomavirus-positive tumors.

All participants received 2 mg/kg pembrolizumab, an anti-PD-1 monoclonal antibody, every 3 weeks for up to 2 years.

Objective response rate, measured by RECIST version 1.1 criteria, served as the primary endpoint. Secondary endpoints included duration of response, PFS and OS.

Median follow-up was 14.9 months (range, 0.4-36.4+).

Results showed an ORR of 56% (95% CI, 41.3-70) to pembrolizumab, including 12 complete responses and 16 partial responses. Researchers observed ORRs of 59% in virus-positive tumors and 53% in virus-negative tumors.

Among the 28 responders, median duration of response was not reached (range, 5.9-34.5+ months).

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The 24-month PFS rate was 48.3%, median PFS was 16.8 months (95% CI, 4.6-not estimable) and the 24-month OS rate was 68.7%. Median OS was not reached.

Investigators noted a trend toward improved PFS and OS among patients with PD-L1-positive tumors.

The overall results compared favorably with historical data of patients who received first-line chemotherapy for advanced Merkel cell carcinoma in two studies. Those data showed only 6% of patients with persistent responses at 18 to 24 months, median PFS of 3.1 months and 4.6 months, and median OS of 9.5 months and 10.2 months.

In the pembrolizumab study, Grade 3 or greater treatment-related adverse events occurred in 14 patients, with seven discontinuing treatment due to these events. Researchers reported one treatment-related death.

The results of the study supported the FDA accelerated approval of pembrolizumab as first-line treatment for adults and children with recurrent or locally advanced or metastatic Merkel cell carcinoma.

“Merkel cell carcinoma is indeed an immunogenic cancer, very similar to that found in other types of skin cancer, especially the most lethal form of skin cancer, melanoma,” Riker said. “Pembrolizumab has not been extensively examined for the more common, and less lethal forms of skin cancer, such as basal cell and squamous cell carcinoma.”– by John DeRosier

For more information:

Adam Riker, MD, FACS, can be reached at Louisiana State University School of Medicine, 7th floor, 1542 Tulane Ave., New Orleans, LA 70112; email: ariker@lsuhsc.edu

Disclosures: Riker reports a consultant or advisory role with Novartis and honoraria and speakers’ bureau fees from Castle Biosciences and Genomic Health. Please see the study for all other authors’ relevant financial disclosures.

 

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