ASCO: APF530 superior to ondansetron in prevention of CINV

SAN FRANCISCO – APF530 is a long-acting 5-HT3 antagonist formulation in development for the prevention of chemotherapy-induced nausea and vomiting, and new data presented at the 2015 Breast Cancer Symposium suggest that it may have an edge over the standard regimen.

When administered with fosaprepitant and dexamethasone, it was superior to ondansetron, in combination with the same two agents, for preventing chemotherapy-induced nausea and vomiting (CINV) associated with delayed ( > 24-120 h) highly emetogenic chemotherapy (HEC).

Among the 450 patients who received the three-drug APF530 combination, 263 (58.4%) experienced a complete response, defined as having no emesis or need for rescue medication, as compared with 239/452 (53%) who received the ondansetron regimen (P= .092).

“APF530 is the first and only 5-HT3 receptor antagonist to demonstrate superiority in a phase III, three-drug versus three-drug regimen efficacy trial for the prevention of CINV in patients receiving HEC,” said Dr. Ian D. Schnadig, from Compass Oncology, The US Oncology Network, Tualatin, OR. “Managing delayed-phase CINV associated with HEC is an unmet need.”

APF530 is a novel, injectable, extended-release version of granisetron that provides sustained release over ≥ 5 days to prevent both acute (0-24 h) and delayed CINV. A large randomized double blind phase III trial has already demonstrated that this new agent is non-inferior to palonosetron in this setting.

In this double-blind, multicenter study known as the MAGIC trial, Dr. Schnadig randomized 902 patients to receive APF530 500 mg by subcutaneous injection (10 mg granisetron) or ondansetron 0.15 mg/kg IV, and the cohort was stratified by planned cisplatin therapy ( ≥ 50 mg/m²).

The primary end point was delayed-phase complete response, and secondary end points included complete response in acute and overall phases and complete control (complete response and no more than mild nausea) in acute, delayed, and overall phases.

A significantly higher percentage of patients in the APF530 cohort (65%) had delayed-phase complete response, as compared to those with ondansetron (57%) (P= .014). In addition, a significantly higher percentage (61% vs. 53%) of patients had delayed-phase complete control (P= .022).

The rates of complete response and complete control in acute and overall phases were numerically higher with APF530 compared with ondansetron, but this did not reach statistical significance.

In looking at exploratory efficacy end points, the authors observed that the proportion of patients who experienced an episode of nausea was generally higher with ondansetron than with APF530. Rates of no nausea were also numerically higher with APF530 compared with the ondansetron regimen in the delayed 49.7% vs. 44.25%; P= .099) and overall phases (45.3% vs. 44.2%; P= .138), but there were no statistically significant differences.

The regimen containing APR530 was generally well tolerated, without any new safety signals identified. The most common treatment related events were injection-site reactions, which were mostly mild or moderate. Injection site reactions were similar between the two groups, Dr. Schnadig noted.

In a discussion of the paper, Dr. Clifford Hudis reiterated that there was a higher complete response rate in late phase with APF530—“that’s an advantage and it was 8% higher in absolute terms, and it was 11% higher in the cisplatin group.”

If the drug is approved and it’s comparably priced to other agents and available, “why wouldn’t you use it?” he asked. “Its more convenient, it’s a little more effective, and its one less thing for all of us practicing to think very much about.”

SAN FRANCISCO – APF530 is a long-acting 5-HT3 antagonist formulation in development for the prevention of chemotherapy-induced nausea and vomiting, and new data presented at the 2015 Breast Cancer Symposium suggest that it may have an edge over the standard regimen.

When administered with fosaprepitant and dexamethasone, it was superior to ondansetron, in combination with the same two agents, for preventing chemotherapy-induced nausea and vomiting (CINV) associated with delayed ( > 24-120 h) highly emetogenic chemotherapy (HEC).

Among the 450 patients who received the three-drug APF530 combination, 263 (58.4%) experienced a complete response, defined as having no emesis or need for rescue medication, as compared with 239/452 (53%) who received the ondansetron regimen (P= .092).

“APF530 is the first and only 5-HT3 receptor antagonist to demonstrate superiority in a phase III, three-drug versus three-drug regimen efficacy trial for the prevention of CINV in patients receiving HEC,” said Dr. Ian D. Schnadig, from Compass Oncology, The US Oncology Network, Tualatin, OR. “Managing delayed-phase CINV associated with HEC is an unmet need.”

APF530 is a novel, injectable, extended-release version of granisetron that provides sustained release over ≥ 5 days to prevent both acute (0-24 h) and delayed CINV. A large randomized double blind phase III trial has already demonstrated that this new agent is non-inferior to palonosetron in this setting.

In this double-blind, multicenter study known as the MAGIC trial, Dr. Schnadig randomized 902 patients to receive APF530 500 mg by subcutaneous injection (10 mg granisetron) or ondansetron 0.15 mg/kg IV, and the cohort was stratified by planned cisplatin therapy ( ≥ 50 mg/m²).

The primary end point was delayed-phase complete response, and secondary end points included complete response in acute and overall phases and complete control (complete response and no more than mild nausea) in acute, delayed, and overall phases.

A significantly higher percentage of patients in the APF530 cohort (65%) had delayed-phase complete response, as compared to those with ondansetron (57%) (P= .014). In addition, a significantly higher percentage (61% vs. 53%) of patients had delayed-phase complete control (P= .022).

The rates of complete response and complete control in acute and overall phases were numerically higher with APF530 compared with ondansetron, but this did not reach statistical significance.

In looking at exploratory efficacy end points, the authors observed that the proportion of patients who experienced an episode of nausea was generally higher with ondansetron than with APF530. Rates of no nausea were also numerically higher with APF530 compared with the ondansetron regimen in the delayed 49.7% vs. 44.25%; P= .099) and overall phases (45.3% vs. 44.2%; P= .138), but there were no statistically significant differences.

The regimen containing APR530 was generally well tolerated, without any new safety signals identified. The most common treatment related events were injection-site reactions, which were mostly mild or moderate. Injection site reactions were similar between the two groups, Dr. Schnadig noted.

In a discussion of the paper, Dr. Clifford Hudis reiterated that there was a higher complete response rate in late phase with APF530—“that’s an advantage and it was 8% higher in absolute terms, and it was 11% higher in the cisplatin group.”

If the drug is approved and it’s comparably priced to other agents and available, “why wouldn’t you use it?” he asked. “Its more convenient, it’s a little more effective, and its one less thing for all of us practicing to think very much about.”

SAN FRANCISCO – APF530 is a long-acting 5-HT3 antagonist formulation in development for the prevention of chemotherapy-induced nausea and vomiting, and new data presented at the 2015 Breast Cancer Symposium suggest that it may have an edge over the standard regimen.

When administered with fosaprepitant and dexamethasone, it was superior to ondansetron, in combination with the same two agents, for preventing chemotherapy-induced nausea and vomiting (CINV) associated with delayed ( > 24-120 h) highly emetogenic chemotherapy (HEC).

Among the 450 patients who received the three-drug APF530 combination, 263 (58.4%) experienced a complete response, defined as having no emesis or need for rescue medication, as compared with 239/452 (53%) who received the ondansetron regimen (P= .092).

“APF530 is the first and only 5-HT3 receptor antagonist to demonstrate superiority in a phase III, three-drug versus three-drug regimen efficacy trial for the prevention of CINV in patients receiving HEC,” said Dr. Ian D. Schnadig, from Compass Oncology, The US Oncology Network, Tualatin, OR. “Managing delayed-phase CINV associated with HEC is an unmet need.”

APF530 is a novel, injectable, extended-release version of granisetron that provides sustained release over ≥ 5 days to prevent both acute (0-24 h) and delayed CINV. A large randomized double blind phase III trial has already demonstrated that this new agent is non-inferior to palonosetron in this setting.

In this double-blind, multicenter study known as the MAGIC trial, Dr. Schnadig randomized 902 patients to receive APF530 500 mg by subcutaneous injection (10 mg granisetron) or ondansetron 0.15 mg/kg IV, and the cohort was stratified by planned cisplatin therapy ( ≥ 50 mg/m²).

The primary end point was delayed-phase complete response, and secondary end points included complete response in acute and overall phases and complete control (complete response and no more than mild nausea) in acute, delayed, and overall phases.

A significantly higher percentage of patients in the APF530 cohort (65%) had delayed-phase complete response, as compared to those with ondansetron (57%) (P= .014). In addition, a significantly higher percentage (61% vs. 53%) of patients had delayed-phase complete control (P= .022).

The rates of complete response and complete control in acute and overall phases were numerically higher with APF530 compared with ondansetron, but this did not reach statistical significance.

In looking at exploratory efficacy end points, the authors observed that the proportion of patients who experienced an episode of nausea was generally higher with ondansetron than with APF530. Rates of no nausea were also numerically higher with APF530 compared with the ondansetron regimen in the delayed 49.7% vs. 44.25%; P= .099) and overall phases (45.3% vs. 44.2%; P= .138), but there were no statistically significant differences.

The regimen containing APR530 was generally well tolerated, without any new safety signals identified. The most common treatment related events were injection-site reactions, which were mostly mild or moderate. Injection site reactions were similar between the two groups, Dr. Schnadig noted.

In a discussion of the paper, Dr. Clifford Hudis reiterated that there was a higher complete response rate in late phase with APF530—“that’s an advantage and it was 8% higher in absolute terms, and it was 11% higher in the cisplatin group.”

If the drug is approved and it’s comparably priced to other agents and available, “why wouldn’t you use it?” he asked. “Its more convenient, it’s a little more effective, and its one less thing for all of us practicing to think very much about.”