Avelumab safety compares with other checkpoint inhibitors

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.